Showing papers by "New York University published in 2007"

Signal integration in the endoplasmic reticulum unfolded protein response

Abstract: The endoplasmic reticulum (ER) responds to the accumulation of unfolded proteins in its lumen (ER stress) by activating intracellular signal transduction pathways - cumulatively called the unfolded protein response (UPR). Together, at least three mechanistically distinct arms of the UPR regulate the expression of numerous genes that function within the secretory pathway but also affect broad aspects of cell fate and the metabolism of proteins, amino acids and lipids. The arms of the UPR are integrated to provide a response that remodels the secretory apparatus and aligns cellular physiology to the demands imposed by ER stress.

Market liquidity and funding liquidity

Abstract: We provide a model that links an asset's market liquidity - i.e., the ease with which it is traded - and traders' funding liquidity - i.e., the ease with which they can obtain funding. Traders provide market liquidity, and their ability to do so depends on their availability of funding. Conversely, traders' funding, i.e., their capital and the margins they are charged, depend on the assets' market liquidity. We show that, under certain conditions, margins are destabilizing and market liquidity and funding liquidity are mutually reinforcing, leading to liquidity spirals. The model explains the empirically documented features that market liquidity (i) can suddenly dry up, (ii) has commonality across securities, (iii) is related to volatility, (iv) is subject to “flight to quality¶, and (v) comoves with the market, and it provides new testable predictions. Keywords: Liquidity Risk Management, Liquidity, Liquidation, Systemic Risk, Leverage, Margins, Haircuts, Value-at-Risk, Counterparty Credit Risk

A survey of named entity recognition and classification

Abstract: This survey covers fifteen years of research in the Named Entity Recognition and Classification (NERC) field, from 1991 to 2006. We report observations about languages, named entity types, domains and textual genres studied in the literature. From the start, NERC systems have been developed using hand-made rules, but now machine learning techniques are widely used. These techniques are surveyed along with other critical aspects of NERC such as features and evaluation methods. Features are word-level, dictionary-level and corpus-level representations of words in a document. Evaluation techniques, ranging from intuitive exact match to very complex matching techniques with adjustable cost of errors, are an indisputable key to progress.

Novel cell death program leads to neutrophil extracellular traps

Abstract: Neutrophil extracellular traps (NETs) are extracellular structures composed of chromatin and granule proteins that bind and kill microorganisms. We show that upon stimulation, the nuclei of neutrophils lose their shape, and the eu- and heterochromatin homogenize. Later, the nuclear envelope and the granule membranes disintegrate, allowing the mixing of NET components. Finally, the NETs are released as the cell membrane breaks. This cell death process is distinct from apoptosis and necrosis and depends on the generation of reactive oxygen species (ROS) by NADPH oxidase. Patients with chronic granulomatous disease carry mutations in NADPH oxidase and cannot activate this cell-death pathway or make NETs. This novel ROS-dependent death allows neutrophils to fulfill their antimicrobial function, even beyond their lifespan.

Investor Sentiment in the Stock Market

Abstract: Investor sentiment, defined broadly, is a belief about future cash flows and investment risks that is not justified by the facts at hand. The question is no longer whether investor sentiment affects stock prices, but how to measure investor sentiment and quantify its effects. One approach is "bottom up," using biases in individual investor psychology, such as overconfidence, representativeness, and conservatism, to explain how individual investors underreact or overreact to past returns or fundamentals. The investor sentiment approach that we develop in this paper is, by contrast, distinctly "top down" and macroeconomic: we take the origin of investor sentiment as exogenous and focus on its empirical effects. We show that it is quite possible to measure investor sentiment and that waves of sentiment have clearly discernible, important, and regular effects on individual firms and on the stock market as a whole. The top-down approach builds on the two broader and more irrefutable assumptions of behavioral finance -- sentiment and the limits to arbitrage -- to explain which stocks are likely to be most affected by sentiment. In particular, stocks that are difficult to arbitrage or to value are most affected by sentiment.

IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways.

Abstract: T helper cells that produce interleukin 17 (IL-17; 'T(H)-17 cells') are a distinct subset of proinflammatory cells whose in vivo function requires IL-23 but whose in vitro differentiation requires only IL-6 and transforming growth factor-beta (TGF-beta). We demonstrate here that IL-6 induced expression of IL-21 that amplified an autocrine loop to induce more IL-21 and IL-23 receptor in naive CD4(+) T cells. Both IL-21 and IL-23, along with TGF-beta, induced IL-17 expression independently of IL-6. The effects of IL-6 and IL-21 depended on STAT3, a transcription factor required for the differentiation of T(H)-17 cells in vivo. IL-21 and IL-23 induced the orphan nuclear receptor RORgammat, which in synergy with STAT3 promoted IL-17 expression. IL-6 therefore orchestrates a series of 'downstream' cytokine-dependent signaling pathways that, in concert with TGF-beta, amplify RORgammat-dependent differentiation of T(H)-17 cells.

K-corrections and filter transformations in the ultraviolet, optical, and near infrared

Abstract: Template fits to observed galaxy fluxes allow calculation of K-corrections and conversions among observations of galaxies at various wavelengths. We present a method for creating model-based template sets given a set of heterogeneous photometric and spectroscopic galaxy data. Our technique, nonnegative matrix factorization, is akin to principal component analysis (PCA), except that it is constrained to produce nonnegative templates, it can use a basis set of models (rather than the delta-function basis of PCA), and it naturally handles uncertainties, missing data, and heterogeneous data (including broadband fluxes at various redshifts). The particular implementation we present here is suitable for ultraviolet, optical, and near-infrared observations in the redshift range 0 < z < 1.5. Since we base our templates on stellar population synthesis models, the results are interpretable in terms of approximate stellar masses and star formation histories. We present templates fitted with this method to data from Galaxy Evolution Explorer, Sloan Digital Sky Survey spectroscopy and photometry, the Two Micron All Sky Survey, the Deep Extragalactic Evolutionary Probe, and the Great Observatories Origins Deep Survey. In addition, we present software for using such data to estimate K-corrections.

MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib

Abstract: In human lung adenocarcinomas harboring EGFR mutations, a second-site point mutation that substitutes methionine for threonine at position 790 (T790M) is associated with approximately half of cases of acquired resistance to the EGFR kinase inhibitors, gefitinib and erlotinib. To identify other potential mechanisms that contribute to disease progression, we used array-based comparative genomic hybridization (aCGH) to compare genomic profiles of EGFR mutant tumors from untreated patients with those from patients with acquired resistance. Among three loci demonstrating recurrent copy number alterations (CNAs) specific to the acquired resistance set, one contained the MET proto-oncogene. Collectively, analysis of tumor samples from multiple independent patient cohorts revealed that MET was amplified in tumors from 9 of 43 (21%) patients with acquired resistance but in only two tumors from 62 untreated patients (3%) (P = 0.007, Fisher's Exact test). Among 10 resistant tumors from the nine patients with MET amplification, 4 also harbored the EGFRT790M mutation. We also found that an existing EGFR mutant lung adenocarcinoma cell line, NCI-H820, harbors MET amplification in addition to a drug-sensitive EGFR mutation and the T790M change. Growth inhibition studies demonstrate that these cells are resistant to both erlotinib and an irreversible EGFR inhibitor (CL-387,785) but sensitive to a multikinase inhibitor (XL880) with potent activity against MET. Taken together, these data suggest that MET amplification occurs independently of EGFRT790M mutations and that MET may be a clinically relevant therapeutic target for some patients with acquired resistance to gefitinib or erlotinib.

When Morality Opposes Justice: Conservatives Have Moral Intuitions that Liberals May Not Recognize

Abstract: Researchers in moral psychology and social justice have agreed that morality is about matters of harm, rights, and justice. With this definition of morality, conservative opposition to social justice programs has appeared to be immoral, and has been explained as a product of various non-moral processes, such as system justification or social dominance orientation. In this article we argue that, from an anthropological perspective, the moral domain is usually much broader, encompassing many more aspects of social life and valuing institutions as much or more than individuals. We present theoretical and empirical reasons for believing that there are in fact five psychological systems that provide the foundations for the world's many moralities. The five foundations are psychological preparations for detecting and reacting emotionally to issues related to harm/care, fairness/reciprocity, ingroup/loyalty, authority/respect, and purity/sanctity. Political liberals have moral intuitions primarily based upon the first two foundations, and therefore misunderstand the moral motivations of political conservatives, who generally rely upon all five foundations.

The evolution of gene regulation by transcription factors and microRNAs

Abstract: Changes in the patterns of gene expression are widely believed to underlie many of the phenotypic differences within and between species. Although much emphasis has been placed on changes in transcriptional regulation, gene expression is regulated at many levels, all of which must ultimately be studied together to obtain a complete picture of the evolution of gene expression. Here we compare the evolution of transcriptional regulation and post-transcriptional regulation that is mediated by microRNAs, a large class of small, non-coding RNAs in plants and animals, focusing on the evolution of the individual regulators and their binding sites. As an initial step towards integrating these mechanisms into a unified framework, we propose a simple model that describes the transcriptional regulation of new microRNA genes.

Woodsmoke Health Effects: A Review

Abstract: The sentiment that woodsmoke, being a natural substance, must be benign to humans is still sometimes heard. It is now well established, however, that wood-burning stoves and fireplaces as well as wildland and agricultural fires emit significant quantities of known health-damaging pollutants, including several carcinogenic compounds. Two of the principal gaseous pollutants in woodsmoke, CO and NOx, add to the atmospheric levels of these regulated gases emitted by other combustion sources. Health impacts of exposures to these gases and some of the other woodsmoke constituents (e.g., benzene) are well characterized in thousands of publications. As these gases are indistinguishable no matter where they come from, there is no urgent need to examine their particular health implications in woodsmoke. With this as the backdrop, this review approaches the issue of why woodsmoke may be a special case requiring separate health evaluation through two questions. The first question we address is whether woodsmoke should be regulated and/or managed separately, even though some of its separate constituents are already regulated in many jurisdictions. The second question we address is whether woodsmoke particles pose different levels of risk than other ambient particles of similar size. To address these two key questions, we examine several topics: the chemical and physical nature of woodsmoke; the exposures and epidemiology of smoke from wildland fires and agricultural burning, and related

Interfirm Collaboration Networks: The Impact of Large-Scale Network Structure on Firm Innovation

Abstract: The structure of alliance networks influences their potential for knowledge creation. Dense local clustering provides information transmission capacity in the network by fostering communication and cooperation. Nonredundant connections contract the distance between firms and give the network greater reach by tapping a wider range of knowledge resources. We propose that firms embedded in alliance networks that exhibit both high clustering and high reach (short average path lengths to a wide range of firms) will have greater innovative output than firms in networks that do not exhibit these characteristics. We find support for this proposition in a longitudinal study of the patent performance of 1,106 firms in 11 industry-level alliance networks.

Unsupervised Learning of Invariant Feature Hierarchies with Applications to Object Recognition

Abstract: We present an unsupervised method for learning a hierarchy of sparse feature detectors that are invariant to small shifts and distortions. The resulting feature extractor consists of multiple convolution filters, followed by a feature-pooling layer that computes the max of each filter output within adjacent windows, and a point-wise sigmoid non-linearity. A second level of larger and more invariant features is obtained by training the same algorithm on patches of features from the first level. Training a supervised classifier on these features yields 0.64% error on MNIST, and 54% average recognition rate on Caltech 101 with 30 training samples per category. While the resulting architecture is similar to convolutional networks, the layer-wise unsupervised training procedure alleviates the over-parameterization problems that plague purely supervised learning procedures, and yields good performance with very few labeled training samples.

Myofibroblast contraction activates latent TGF-β1 from the extracellular matrix

Abstract: The conjunctive presence of mechanical stress and active transforming growth factor beta1 (TGF-beta1) is essential to convert fibroblasts into contractile myofibroblasts, which cause tissue contractures in fibrotic diseases. Using cultured myofibroblasts and conditions that permit tension modulation on the extracellular matrix (ECM), we establish that myofibroblast contraction functions as a mechanism to directly activate TGF-beta1 from self-generated stores in the ECM. Contraction of myofibroblasts and myofibroblast cytoskeletons prepared with Triton X-100 releases active TGF-beta1 from the ECM. This process is inhibited either by antagonizing integrins or reducing ECM compliance and is independent from protease activity. Stretching myofibroblast-derived ECM in the presence of mechanically apposing stress fibers immediately activates latent TGF-beta1. In myofibroblast-populated wounds, activation of the downstream targets of TGF-beta1 signaling Smad2/3 is higher in stressed compared to relaxed tissues despite similar levels of total TGF-beta1 and its receptor. We propose activation of TGF-beta1 via integrin-mediated myofibroblast contraction as a potential checkpoint in the progression of fibrosis, restricting autocrine generation of myofibroblasts to a stiffened ECM.

Whom You Know Matters: Venture Capital Networks and Investment Performance

Abstract: Many financial markets are characterized by strong relationships and networks, rather than arm’s-length, spot market transactions. We examine the performance consequences of this organizational structure in the context of relationships established when VCs syndicate portfolio company investments. We find that better-networked VC firms experience significantly better fund performance, as measured by the proportion of investments that are successfully exited through an IPO or a sale to another company. Similarly, the portfolio companies of better-networked VCs are significantly more likely to survive to subsequent financing and eventual exit. We also provide initial evidence on the evolution of VC networks. NETWORKS ARE WIDESPREAD IN MANY FINANCIAL MARKETS. Bulge-bracket investment banks, for instance, make use of strong relationships with institutional investors when pricing and distributing corporate securities (Cornelli and Goldreich (2001)). In the corporate loan market, banks often prefer syndicating loans with other banks over being the sole lender. Similarly, in the primary equity and bond markets, banks tend to co-underwrite securities offerings with banks with which they have longstanding relationships (Ljungqvist, Marston, and Wilhelm (2005)). Networks also feature prominently in the venture capital (VC) industry. VCs tend to syndicate their investments with other VCs, rather than investing alone (Lerner (1994a)). They are thus bound by their current and past investments into webs of relationships with other VCs. Once they have invested in a company, VCs draw on their networks of service providers—head hunters, patent lawyers, investment bankers, etc.—to help the company succeed (Gorman and Sahlman (1989), and Sahlman (1990)). Indeed, one prominent VC goes as far

Dust Masses, PAH Abundances, and Starlight Intensities in the SINGS Galaxy Sample

Abstract: Physical dust models are presented for 65 galaxies in SINGS that are strongly detected in the four IRAC bands and three MIPS bands. For each galaxy we estimate (1) the total dust mass, (2) the fraction of the dust mass contributed by PAHs, and (3) the intensity of the starlight heating the dust grains. We find that spiral galaxies have dust properties resembling the dust in the local region of the Milky Way, with similar dust-to-gas ratio and similar PAH abundance. The observed SEDs, including galaxies with SCUBA photometry, can be reproduced by dust models that do not require "cold" (T ≾ 10 K) dust. The dust-to-gas ratio is observed to be dependent on metallicity. In the interstellar media of galaxies with A_O ≡ 12 + log_(10)(O/H) > 8.1, grains contain a substantial fraction of interstellar Mg, Si, and Fe. Galaxies with A_O 8.1 have a median q_(PAH) = 3.55%. The derived dust masses favor a value X_(CO) ≈ 4 × 10^(20) cm^(-2) (K km s^(-1))^(-1) for the CO-to-H_2 conversion factor. Except for some starbursting systems (Mrk 33, Tol 89, NGC 3049), dust in the diffuse ISM dominates the IR power.

A Measurement Study of a Large-Scale P2P IPTV System

Abstract: An emerging Internet application, IPTV, has the potential to flood Internet access and backbone ISPs with massive amounts of new traffic. Although many architectures are possible for IPTV video distribution, several mesh-pull P2P architectures have been successfully deployed on the Internet. In order to gain insights into mesh-pull P2P IPTV systems and the traffic loads they place on ISPs, we have undertaken an in-depth measurement study of one of the most popular IPTV systems, namely, PPLive. We have developed a dedicated PPLive crawler, which enables us to study the global characteristics of the mesh-pull PPLive system. We have also collected extensive packet traces for various different measurement scenarios, including both campus access networks and residential access networks. The measurement results obtained through these platforms bring important insights into P2P IPTV systems. Specifically, our results show the following. 1) P2P IPTV users have the similar viewing behaviors as regular TV users. 2) During its session, a peer exchanges video data dynamically with a large number of peers. 3) A small set of super peers act as video proxy and contribute significantly to video data uploading. 4) Users in the measured P2P IPTV system still suffer from long start-up delays and playback lags, ranging from several seconds to a couple of minutes. Insights obtained in this study will be valuable for the development and deployment of future P2P IPTV systems.

The Calibration of Mid-Infrared Star Formation Rate Indicators

Abstract: With the goal of investigating the degree to which the MIR emission traces the SFR, we analyze Spitzer 8 and 24 μm data of star-forming regions in a sample of 33 nearby galaxies with available HST NICMOS images in the Paα (1.8756 μm) emission line. The galaxies are drawn from the SINGS sample and cover a range of morphologies and a factor ~10 in oxygen abundance. Published data on local low-metallicity starburst galaxies and LIRGs are also included in the analysis. Both the stellar continuum-subtracted 8 μm emission and the 24 μm emission correlate with the extinction-corrected Paα line emission, although neither relationship is linear. Simple models of stellar populations and dust extinction and emission are able to reproduce the observed nonlinear trend of the 24 μm emission versus number of ionizing photons, including the modest deficiency of 24 μm emission in the low-metallicity regions, which results from a combination of decreasing dust opacity and dust temperature at low luminosities. Conversely, the trend of the 8 μm emission as a function of the number of ionizing photons is not well reproduced by the same models. The 8 μm emission is contributed, in larger measure than the 24 μm emission, by dust heated by nonionizing stellar populations, in addition to the ionizing ones, in agreement with previous findings. Two SFR calibrations, one using the 24 μm emission and the other using a combination of the 24 μm and Hα luminosities (Kennicutt and coworkers), are presented. No calibration is presented for the 8 μm emission because of its significant dependence on both metallicity and environment. The calibrations presented here should be directly applicable to systems dominated by ongoing star formation.

Authoritarian Institutions and the Survival of Autocrats

Abstract: Why do some autocrats survive for decades, and others fall soon after taking power? The authors argue that when authoritarian rulers need to solicit the cooperation of outsiders or deter the threat...

Financial Constraints, Asset Tangibility, and Corporate Investment

Abstract: This paper proposes a new strategy to identify the eect of …nancial constraints on corporate investment. When …rms are able to pledge their assets as collateral, investment and borrowing become endogenous: pledgeable assets support more borrowings that in turn allow for further investments in pledgeable assets. We show that this credit multiplier has a …rst-order eect on investment when …rms face …nancing frictions. In particular, investment-cash ‡ow sensitivities will be increasing in the degree of tangibility of constrained …rms' assets. When …rms are unconstrained, in contrast, investment-cash ‡ow sensitivities are unaected by asset tangibility. This theoretical prediction allows us to use a "dierences in dierences" approach to identify the eect of …nancing frictions on corporate investment: we compare the dierential (marginal) eect of asset tangibility on the sensitivity of investment to cash ‡ow across dierent regimes of …nancial constraints. Using two layers of cross-sectional contrasts sidesteps concerns that cash ‡ows might correlate with a …rm's (residual) investment opportunities when Q fails as a control. We implement our testing strategy on a large sample of …rms drawn from COMPUSTAT between 1971 and 2000. The data strongly support our hypothesis about the role of asset tangibility on corporate investment under …nancial constraints.

Corporate Governance and Risk Taking

Abstract: This paper examines the relationship between investor protection and corporate insiders' incentive to take value-enhancing risks. In a poor investor protection environment corporations are often run by entrenched insiders who appropriate considerable corporate resources as personal benefits. When these private benefits are large, insiders may undertake sub-optimally conservative investment decisions to preserve them. Better investor protection reduces these private benefits and may therefore induce riskier but value enhancing investment policy. Such a relationship can also result from risk-averse behavior on the part of dominant shareholders with undiversified exposure in their own firms, which is again more prevalent in countries with poorer investor protection. If prominent non-equity stakeholders such as banks, labor unions or the government can influence corporate investment, and their influence is decreasing in investor protection, that can also give rise to a positive relationship between investor protection and investment risk. We test these predictions using a large cross-country panel. We find empirical confirmation that corporate risk-taking and firm growth rates are positively related to the quality of investor protection. On the other hand, the data do not lead to consistent evidence for the alternative channels.

Calcium signalling in lymphocyte activation and disease.

Abstract: Calcium signals in cells of the immune system participate in the regulation of cell differentiation, gene transcription and effector functions. An increase in intracellular levels of calcium ions (Ca2+) results from the engagement of immunoreceptors, such as the T-cell receptor, B-cell receptor and Fc receptors, as well as chemokine and co-stimulatory receptors. The major pathway that induces an increase in intracellular Ca2+ levels in lymphocytes is through store-operated calcium entry (SOCE) and calcium-release-activated calcium (CRAC) channels. This Review focuses on the role of Ca2+ signals in lymphocyte functions, the signalling pathways leading to Ca2+ influx, the function of the recently discovered regulators of Ca2+ influx (STIM and ORAI), and the relationship between Ca2+ signals and diseases of the immune system.