cssi/SciSciGPT-SciSciNet huggingface dataset:
Sudden Stops, the Real Exchange Rate and Fiscal Sustainability in Argentina

HE fall of convertibility in Argentina has stirred a lively discussion aboutthe causes for its collapse. Several explanations have been offered. Themost popular one relates to the unsustainable combination of a fixed exchangerate and large fiscal deficits that led to a rapid growth in public debt, severe fiscalproblems, and eventually, a loss of access to credit markets. Another popularview stresses the impact of devaluation by Argentina’s major trading partners asan important cause of real exchange rate (RER) misalignment, which reducedprofitability in the tradable sector. This, in turn, slowed down investment and ledthe economy into a protracted recession, with the associated deflation being themechanism for easing the RER disequilibrium.Here a different interpretation of the collapse of convertibility is provided,drawing heavily on recent work by Calvo et al. (2002). This interpretation shareswith the previous views the acknowledgement of fiscal sustainability problemsand RER misalignment. However, this view places special emphasis on financialconsiderations. In particular, it is argued that the impact of RER misalignmentwent beyond considerations of trade and competitiveness. It played a major rolein the fiscal and financial problems that eventually Argentina had to confront.Moreover, fixed exchange rates helped conceal those problems and, as a result,necessary fiscal measures were postponed, thereby intensifying the crisis.
Marching to the Beat of Different Drummers: The Influence of Institutional Owners on Competitive Actions

This research extends agency theory by exploring the influence of varied, competing, principal interests on executive actions. Findings reveal that ownership of a firm by dedicated institutional investors, who hold concentrated portfolios over time, is positively associated with firm use of strategic competitive actions. Ownership by transient institutional investors, who hold broad portfolios and make frequent trades based on current earnings, is negatively associated with strategic competitive actions and positively associated with tactical ones. Appreciable ownership of the same firm by these two classes of investors influences both strategic and tactical competitive actions. These results have broad implications for executives, investors, and policy makers.
Stock Market Returns and Liquidity: Dynamic Relationships and Causality

This article examines the impulse response functions and causality test of stock market returns and marketwide liquidity as measured by share turnover (the total number of shares traded over a period divided by the average number of shares outstanding for the period). The analyses of the monthly data spanning from 1926 to 2011 of the NYSE share volume turnover and returns on the NYSE stock portfolios show that the returns on the NYSE value-weighted stock portfolio are immediately negative in the first month following the NYSE share turnover shock; however, the returns become positive five months after the shock. The returns on the NYSE largest stock portfolio are negative for the first five months following the share turnover shock. There is a significant jump in the NYSE share turnover in the first month following the shock of the returns on the NYSE value-weighted and equal-weighted portfolios; this finding is consistent with the overconfidence theory. The causality test results indicate that stock returns and liquidity Granger-cause each other. The results of this study offer important information and implications for investment and risk management.
Reasonableness in and out of Negligence Law

INTRODUCTION 2132 I. VARIANTS IN THE LANGUAGE OF REASONABLENESS 2135 A. Reasonable and Unreasonable 2136 B. Optimizing or Range-Delineating 2136 C. Adjectival Versus Adverbial Modification 2137 II. FAMILIES OF “REASONABLENESS” USE 2138 A. The Antonym of “Excessive” 2138 B. Passable Exercises of Judgment or Interpretative Capacity (and Deference) 2139 C. Reasonableness and Justifiability (Epistemic) 2140 D. Two Kinds of Practical Reasonableness 2142 E. Secondary Qualities in the Law 2143 F. Mixed and Other Categories 2145 III. JURISPRUDENTIAL OBSERVATIONS 2146 A. Standards and Vagueness 2146 B. Two Kinds of Delegation of Judgement Power 2147 C. The Reasonable Person as a Decision-Guiding Device 2148 D. The Normative Versus Descriptive Confusion 2149
A basic model for evaluating R&D performance: theory and application in Italy

Nowadays the public R&D laboratories have a fundamental role in countries’ development, supporting businesses as they face the technological challenges in the turbulent world scenarios. Measuring the performance of R&D organisations is crucially important to decisions about the level and direction of public funding for research and development. This research considers the public laboratories like systems and develops a mathematical model based on the measurement of R&D activities with k-indices. The score obtained from the research laboratories evaluation (relev) methodology synthesises in single value financial, scientific and technological aspects. It is an indicator, for R&D manager and policy maker, of performance in relation to other research organisations or in a time series. The method is an instrument of strategic planning and can be used for the improvement of individual activities and the overall performance of public R&D bodies.
Actuarially Fair Premia for Deductible Insurance Policies

We show how to construct uniform pricing frameworks for various insurance products that have pre-specified deductibles. It is shown that the deductible insurance policies' indemnity payoff functions resemble those of distinctive derivative securities; therefore, the actuarially fair premia can be obtained using option-pricing techniques. We analytically and numerically derive the actuarially fair insurance premium for each of the five most common deductible insurance policies, namely, a proportional deductible insurance policy, a franchise deductible insurance policy, a fixed deductible insurance policy, a disappearing deductible insurance policy, and a deductible insurance policy with an upper limit on coverage. These actuarially fair premia are also depicted graphically, and it is shown that an increase in the insured asset's volatility will increase the premia, ceteris paribus.
Activism in Turkish Foreign Policy: Balancing European and Regional Interests

This article argues that long-term changes in Turkish foreign policy are primarily due to the diversification of the country's political and economic interests. Important international structural shifts such as the end of the Cold War or the broad fluctuations in oil prices have constituted the initial impetus for the changes that we have seen in Turkish policies. Discussing alternative perspectives on new activism in Turkish foreign policy, the article gauges Turkey's foreign policy affinity (based on voting patterns in the United Nations General Assembly) and trade with other states to place recent trends in the broader context of the past three decades. It shows that, as the “West” has become less coherent in its policies, Turkey has moved closer to EU members and distanced itself from the US. The data also undermine “shift of axis” arguments as Turkey's foreign policy affinity with Middle Eastern countries has, in fact, declined. The trade data reveal a diversification of the country's commercial interests that contribute to Turkey's increasing regional activism. The country now balances its long term European interests with its recent regional ones.
On the volatility of volatility

Abstract The Chicago Board Options Exchange (CBOE) Volatility Index, VIX, is calculated based on prices of out-of-the-money put and call options on the S&P 500 index (SPX). Sometimes called the “investor fear gauge”, the VIX is a measure of the implied volatility of the SPX, and is observed to be correlated with the 30-day realized volatility of the SPX. Changes in the VIX are observed to be negatively correlated with changes in the SPX. However, no significant correlation between changes in the VIX and changes in the 30-day realized volatility of the SPX are observed. We investigate whether this indicates a mispricing of options following large VIX moves, and examine the relation to excess returns from variance swaps. The sense in which the term “mispricing” is used is discussed in the paper.
The Gaming of Pharmaceutical Patents

Paragraph IV of the Hatch-Waxman Act provides a mechanism for the litigation of pharmaceutical patent infringement disputes. Many of these cases have been settled with reverse payments by the brand to the generic in return for delayed generic product entry. The Federal Trade Commission (FTC) has contested several of these settlements with good but not complete success. This paper discusses the merits of treating settlements that include side payments or deals that are beneficial to the generic as illegal per se. The paper also describes several additional strategies in addition to side payments, some of which raise serious antitrust problems, that brands have used to keep generics out of the market.
Information Acquisition in Financial Markets

tions: agents have exponential utility, and random variables are normally distributed. These assumptions are often necessary to obtain closed-form solutions. We present an example with alternative assumptions, and demonstrate that some of the conclusions from previous literature fail to hold. In particular, we show that in our example, as more agents acquire information, prices do not necessarily become more informative, and agents may have greater incentive to acquire informatioln. Learning can therefore be a strategic complement, allowing for the possibility of multiple equilibria.
Financial markets, fiscal constraints, and municipal debt: lessons and evidence from the panic of 1873

The current paper explores the municipal debt crisis that resulted from the panic of 1873, which caused a significant number of local governments in the United States to default on their debt obligations. The aftermath of that episode was one of constitutional change meant to constrain municipal governments from pursuing similar activities in the future. This paper empirically investigates the impact that these restrictions had on municipal borrowing costs, analyzed from bond yield data taken from several major US financial markets, so as to evaluate how binding and significant markets actually perceived these constraints to be. Overall, the results suggest that borrowing costs were lower for municipal governments that faced more stringent creditor guarantees regarding the issuing and repayment of debt, hard budget constraints, and also strict debt limits, while tax limits generally increased borrowing costs. These results not only conform too much of the current literature regarding the political economy of institutional constraints on public finance, they also add several important insights, especially when comparing defaulting to non-defaulting municipalities.
A Note on Global Welfare in Pharmaceutical Patenting

This paper revisits the question of whether global welfare is higher under a uniform world-wide system of pharmaceutical product patents or with international rules allowing low-income nations to free-ride on the discoveries of firms in rich nations. Key variables include the extent to which free-riding reduces the discovery of new drugs, the rent potential of rich as compared to poor nations, the ratio of the marginal utility of income in poor as compared to rich nations, and the competitive environment within which R&D decisions are made. Global welfare is found to be higher with free-riding across plausible discovery impairment and income utility combinations, especially when rent-seeking behaviour leads to an expansion of R&D outlays exhausting appropriable rents.
Did Board Configuration Matter? The Case of US Subprime Lenders

Manuscript Type: Empirical Research Question/Issue: The origins of the global financial crisis have been attributed to the combination of a housing price bubble and innovative financial instruments, as well as the lack of restraint by corporate executives and boards to engage in excessive risk-taking. The rise in subprime lending between 1997 and 2005 played a crucial role in inflating the housing price bubble. We take a unique dataset of US financial institutions heavily engaged in subprime lending and ask the following research question: Did board configuration play a role in determining whether a financial institution specialized in subprime lending? Research Findings/Insights: We use a matched-pair sample of firms in the financial industry from 1997–2005 with half of the sample specializing in subprime lending and conduct panel data logistic regression analysis. We find that the board configurations of those financial institutions that engaged in subprime lending were significantly different from those that did not. Specifically, subprime lenders had boards that were busier, had less tenure, and were less diverse with respect to gender. Theoretical/Academic Implications: This study uses the group decision making perspective in the context of subprime lending to examine board of director configuration and its influence on decision making processes around the issue of risky subprime lending. Findings show that how boards were configured did influence the decision to specialize in subprime lending. We find robust support for predictions based on the group decision making perspective. Practitioner/Policy Implications: The deterioration of mortgage lending requirements that gave rise to the defaults of so many subprime loans, in retrospect, appears to be something that should have been entirely preventable. By demonstrating that subprime specialists had significant differences in board configuration that impacted group decision making, this study offers guidance to policymakers considering additional regulation and for corporate officers examining corporate governance issues.
Estimating the effect of price limits on limit‐hitting days

Summary This study examines whether price limits affect underlying equilibrium prices on limit-hitting days. To identify two effects—a ceiling effect and a cooling or heating effect (C-H effect)—we use the fact that equilibrium prices are reached at the day immediately after price limits are hit. We estimate the C-H effect by letting the return series be mixture normal to capture the possible 'fat tails.' We apply our models to five randomly selected Taiwanese stocks and all the continuously traded stocks in our sample period. The simple normal density which would lead one to conclude that price limits can 'cool off stock prices is soundly rejected. However, if normal mixture density is used, one would generally conclude that price limits will have no effect on the variance of stock returns.
Mandatory disclosure and asymmetry in financial reporting

This paper examines the demand for disclosure rules by informed managers interested in increasing the market price of their firms. Within a model of political influence, a majority of managers chooses disclosure rules with which all firms must comply. In equilibrium, disclosure rules are asymmetric with greater levels of disclosure over adverse events. This asymmetry is positively associated with the informativeness of the measurement and increasing in the level of verifiability and ex-ante uncertainty of the information. The theory also offers implications about the relation between mandatory and voluntary disclosure, when both channels are endogenous.
The Subjects of the Constitution

Two centuries after Marbury v. Madison, there remains a deep confusion about quite what a court is reviewing when it engages in judicial review. Conventional wisdom has it that judicial review is the review of certain legal objects: statutes, regulations. But strictly speaking, this is not quite right. The Constitution prohibits not objects but actions. Judicial review is the review of such actions. And actions require actors: verbs require subjects. So before judicial review focuses on verbs, let alone objects, it should begin at the beginning, with subjects. Every constitutional inquiry should begin with a basic question that has been almost universally overlooked. The fundamental question, from which all else follows, is the who question: who has violated the Constitution?As judicial review is practiced today, courts skip over this bedrock question to get to the more familiar question: how was the Constitution violated? But it makes no sense to ask how, until there is an answer to who. Indeed, in countless muddled lines of doctrine, puzzlement about the predicates of constitutional violation follows directly from more fundamental confusion about the subjects.Confusion about the who (and, relatedly, the when) of constitutional violation has been the root cause of many of the deepest puzzles of federal jurisdiction - puzzles of ripeness, of standing, of severability, of “facial” and “as-applied” challenges. Simply by focusing attention on this crucial constitutional feature, the subjects of the Constitution, these puzzles may be solved once and for all. And as they are solved, it becomes clear that this approach constitutes a new model of judicial review.But the implications of this new paradigm are not limited to federal jurisdiction. It turns out that confusion over the deep puzzles of federal jurisdiction has had subtle but profound feedback effects on substantive constitutional doctrine as well. Once these jurisdictional puzzles are solved, the scope of constitutional rights and powers comes into new focus as well. These implications ripple through the most important and controversial doctrines of constitutional law, from the scope of the Commerce Clause to the reach of the First Amendment, from the meaning of equal protection to the content of privileges and immunities, from the nature of due process to the shape of abortion rights.And all of it derives from nothing more complicated than asking the right first question: who has violated the Constitution?
Monetary policy and long-term interest rates: An efficient markets approach

Abstract This paper is an application of efficient markets theory to analyze empirically the relationship of money supply growth and long-term interest rates. This approach has the advantage over calier research on this subject in that it imposes a theoretical structure on this relationship that flows easier interpretation of the empirical results as well as more powerful statistical tests on the interest of ascertaining the robustness of the results, many different empirical tests are carried out in this paper, and they uniformly do not support the preposition that increases in the money supply are correlated with declines in long rates.
Determinants of the costs of carbon capture and sequestration for expanding electricity generation capacity

Abstract This study models the costs of electricity generation with carbon capture and sequestration (CCS), from generation at the power plant to carbon injection at the reservoir, examining the economic factors that affect technology choice and CCS costs at the individual plant level. The results suggest that natural gas and coal prices have profound impacts on the carbon price needed to induce CCS. To extend previous analyses we develop a "cost region" graph that models technology choice as a function of carbon and fuel prices. Generally, the least-cost technology at low carbon prices is pulverized coal, while intermediate carbon prices favor natural gas technologies and high carbon prices favor coal gasification with capture. However, the specific carbon prices at which these transitions occur is largely determined by the price of natural gas. For instance, the CCS-justifying carbon price ranges from $27/t CO2 at high natural gas prices to $54/t CO2 at low natural gas prices. This result has important implications for potential climate change legislation. The capital costs of the generation and CO2 capture plant are also highly important, while pipeline distance and criteria pollutant control are less significant.
The Correlation Structure of Unexpected Returns in U.S. Equities

We examine the correlations between unexpected market moves and unexpected equity portfolio moves conditional on market performance. We derive unexpected returns from a two-stage regime switching model. The model allows for time-varying expected returns where the market portfolio alone dictates the regime switching process. Portfolios exhibit a natural hedge where correlations during extreme unexpected market downturns are generally negative. During unexpected market upswings, correlations increase. Using the unconditional analysis would lead to overhedging during market downturns and underhedging during market upswings. The adjustments to the unconditional hedging strategy conditional on extreme market movements frequently exceed ±10%.
Dynamic Portfolio Choice with Linear Rebalancing Rules

We consider a broad class of dynamic portfolio optimization problems that allow for complex models of return predictability, transaction costs, trading constraints, and risk considerations. Determining an optimal policy in this general setting is almost always intractable. We propose a class of linear rebalancing rules and describe an efficient computational procedure to optimize with this class. We illustrate this method in the context of portfolio execution and show that it achieves near optimal performance. We consider another numerical example involving dynamic trading with mean-variance preferences and demonstrate that our method can result in economically large benefits.
Of Patents and Path Dependency: A Comment on Burk and Lemley

This Article delves into issues surrounding the relationship between technology and the patent law. Responding to Dan Burk and Mark Lemley's earlier article, Is Patent Law Technology-Specific?, the piece notes that the basic question posed by Burk and Lemley's article is a relatively easy question given the several doctrines that explicitly link the subject matter context of an invention to the validity and scope of related patents. This sort of technological exceptionalism (which this Article refers to as micro-exceptionalism) is both observable and easily justifiable for a legal regime directed to technology policy. In contrast, Burk and Lemley's identification of, and advocacy for, a broader sort of exceptionalism (macro-exceptionalism) is far more troublesome, implying a role for the patent judiciary in rather detailed policy judgments, for example the optimal breadth for biotechnological or software-based patents. The Article offers a variety of reasons that macro-exceptionalism is unwarranted, and indeed, notes that a primary claim of Burk and Lemley's-that the Federal Circuit has grossly missed the mark in its (purportedly) exceptionalist approach-previews the sort of problems created by pursuing technological exceptionalism in the patent law.
Coming Up for Air: The Constitutionality of Using Eminent Domain to Condemn Underwater Mortgages

Following the Great Recession, home prices in many areas capsized, leaving many homeowners “underwater.” Today, home prices have not yet returned to pre-recession levels, leading many commentators to fear that these underwater mortgages will default and bring about a flood of new foreclosures. Local governments are now contemplating using the power of eminent domain to condemn these mortgages and reduce the principal owed. This move would allow homeowners to build equity and, in turn, reduce the fear of default and foreclosure. This Note analyzes the constitutionality of using eminent domain in this manner and discusses whether it would pass constitutional muster under the Fifth Amendment’s Takings Clause.
(Ad)ministering Justice: A Prosecutor's Ethical Duty to Support Sentencing Reform

This Article stakes out an ethical argument in favor of prosecutorial leadership on sentencing reform. Prosecutors have a duty as “ministers of justice” to go beyond seeking appropriate conviction and punishment in individual cases, and to think about the delivery of criminal justice on a systemic level―promoting criminal justice policies that further broader societal ends. While other authors have explored the tensions between a prosecutor’s adversarial duties and “minister of justice” role in the context of specific litigation, few have explored what it means to be an “administer” of justice in the wider political arena. The author sets forth a new construct of what is required for a prosecutor to be a neutral, nonpartisan “administer of justice” in her legislative and public advocacy activities. Applying this paradigm to the ongoing national debate about sentencing reform, the author argues that a prosecutor’s administrative responsibilities as a leader in the criminal justice establishment and her fiduciary responsibilities as a representative of the sovereign should compel her to join in the effort to repeal mandatory minimum sentencing provisions for most drug and non-violent offenses. Not only are mandatory sentences in most instances inefficacious and unduly coercive, but they allow for an arbitrary and discriminatory application that is essentially unreviewable by courts. The author distinguishes his argument against mandatory minimum penalties from the so-called “Smart on Crime” movement, by grounding a prosecutor’s duty to promote sentencing reform in ethical reasoning as opposed to pragmatic or cost-savings considerations.
A Definite Claim on Claim Indefiniteness: An Empirical Study of Definiteness Cases of the Past Decade with a Focus on the Federal Circuit and the Insolubly Ambiguous Standard

This empirical study of patent claim definiteness cases of the past decade makes several novel findings including: (1) slightly more than half of final Federal Circuit definiteness cases hold the asserted claims not indefinite; (2) the percentage of non-Federal Circuit definiteness cases holding claims not indefinite increased approximately 60 percentage points over the tenyear period focused on in this analysis;(3) the Federal Circuit more often held chemical claims not indefinite, but electrical claims indefinite; and (4) the Federal Circuit more often held claims with term clarity issues not indefinite, but claims with means-plus-function issues indefinite. These differences partially result from the Federal Circuit incorporating an evidentiary burden into the "insolubly ambiguous" standard and inconsistently applying the "insolubly ambiguous" standard. After describing other effects of this standard, this Article recommends that the Federal Circuit modify, clarify, or abolish the "insolubly ambiguous" standard. * Article won second place in the Marcus B. Finnegan Writing Competition. Christa Laser is a third-year law student at the George Washington University Law School. She is a notes editor of the American Intellectual Property Law Association Quarterly Journal and studied abroad at the Max Plank Institute for Intellectual Property, Competition, and Tax Law. 10 Chi.-Kent J. Intell. Prop. 25 Copyright C 2010, Chicago-Kent Journal of Intellectual Property
Does Mortgage Hedging Raise Long-Term Interest Rate Volatility?

An examination of the impact of mortgage hedging activities on interest rate volatility considers a wide range of interest rate derivatives to isolate the sources that might be contributing to volatility. Over a rolling window providing estimates of key parameters, the measured effects of mortgage hedging on volatility are distorted by two outlier episodes: the collapse of Long-Term Capital Management, and the market reaction in the aftermath of the September 2001 events. Eliminating these episodes from the data shows that hedging appears to stabilize rate volatility over some periods while exacerbating it in others. The conclusion: that no simple relationship between hedging and rate volatility is clear.
The Separateness of Persons and Liberal Theory

The fact that persons are separate in some descriptive sense is relatively uncontroversial. But one of the distinctive ideas of contemporary liberal political philosophy is that the descriptive fact of our separateness is normatively momentous. John Rawls and Robert Nozick both take the separateness of persons to provide a foundation for their rejection of utilitarianism and for their own positive political theories. So why do their respective versions of liberalism look so different? This paper claims that the difference is based in Rawls' and Nozick's differing understandings of the morally significant aspects of personhood, and argues that respect for separateness is a value better suited to defend Nozickian libertarianism than Rawlsian liberalism.
Frog in the Pan: Continuous Information and Momentum

We test a frog-in-the-pan (FIP) hypothesis that predicts investors are inattentive to information arriving continuously in small amounts. Intuitively, we hypothesize that a series of frequent gradual changes attracts less attention than infrequent dramatic changes. Consistent with the FIP hypothesis, we find that continuous information induces strong persistent return continuation that does not reverse in the long run. Momentum decreases monotonically from 5.94% for stocks with continuous information during their formation period to �2.07% for stocks with discrete information but similar cumulative formation-period returns. Higher media coverage coincides with discrete information and mitigates the stronger momentum following continuous information.
Stock and bond returns with Moody Investors

We present a tractable, linear model for the simultaneous pricing of stock and bond returns that incorporates stochastic risk aversion. In this model, analytic solutions for endogenous stock and bond prices and returns are readily calculated. After estimating the parameters of the model by the general method of moments, we investigate a series of classic puzzles of the empirical asset pricing literature. In particular, our model is shown to jointly accommodate the mean and volatility of equity and long term bond risk premia as well as salient features of the nominal short rate, the dividend yield, and the term spread. Also, the model matches the evidence for predictability of excess stock and bond returns. However, the stock–bond return correlation implied by the model is somewhat higher than that in the data.
A Bayesian nonparametric approach for inferring drug combination effects on mental health in people with HIV

Although combination antiretroviral therapy (ART) with three or more drugs is highly effective in suppressing viral load for people with HIV (human immunodeficiency virus), many ART agents may exacerbate mental health-related adverse effects including depression. Therefore, understanding the effects of combination ART on mental health can help clinicians personalize medicine with less adverse effects to avoid undesirable health outcomes. The emergence of electronic health records offers researchers' unprecedented access to HIV data including individuals' mental health records, drug prescriptions, and clinical information over time. However, modeling such data is challenging due to high dimensionality of the drug combination space, the individual heterogeneity, and sparseness of the observed drug combinations. To address these challenges, we develop a Bayesian nonparametric approach to learn drug combination effect on mental health in people with HIV adjusting for sociodemographic, behavioral, and clinical factors. The proposed method is built upon the subset-tree kernel that represents drug combinations in a way that synthesizes known regimen structure into a single mathematical representation. It also utilizes a distance-dependent Chinese restaurant process to cluster heterogeneous populations while considering individuals' treatment histories. We evaluate the proposed approach through simulation studies, and apply the method to a dataset from the Women's Interagency HIV Study, showing the clinical utility of our model in guiding clinicians to prescribe informed and effective personalized treatment based on individuals' treatment histories and clinical characteristics.
Triples of rational points on the Hermitian curve and their Weierstrass semigroups

Abstract In this paper, we study configurations of three rational points on the Hermitian curve over F q 2 and classify them according to their Weierstrass semigroups. For q > 3 , we show that the number of distinct semigroups of this form is equal to the number of positive divisors of q + 1 and give an explicit description of the Weierstrass semigroup for each triple of points studied. To do so, we make use of two-point discrepancies and derive a criterion which applies to arbitrary curves over a finite field.
Anti-inflammatory dopamine- and serotonin-based endocannabinoid epoxides reciprocally regulate cannabinoid receptors and the TRPV1 channel

The endocannabinoid system is a promising target to mitigate pain as the endocannabinoids are endogenous ligands of the pain-mediating receptors-cannabinoid receptors 1 and 2 (CB1 and CB2) and TRPV1. Herein, we report on a class of lipids formed by the epoxidation of N-arachidonoyl-dopamine (NADA) and N-arachidonoyl-serotonin (NA5HT) by epoxygenases. EpoNADA and epoNA5HT are dual-functional rheostat modulators of the endocannabinoid-TRPV1 axis. EpoNADA and epoNA5HT are stronger modulators of TRPV1 than either NADA or NA5HT, and epoNA5HT displays a significantly stronger inhibition on TRPV1-mediated responses in primary afferent neurons. Moreover, epoNA5HT is a full CB1 agonist. These epoxides reduce the pro-inflammatory biomarkers IL-6, IL-1β, TNF-α and nitrous oxide and raise anti-inflammatory IL-10 cytokine in activated microglial cells. The epoxides are spontaneously generated by activated microglia cells and their formation is potentiated in the presence of anandamide. Detailed kinetics and molecular dynamics simulation studies provide evidence for this potentiation using the epoxygenase human CYP2J2. Taken together, inflammation leads to an increase in the metabolism of NADA, NA5HT and other eCBs by epoxygenases to form the corresponding epoxides. The epoxide metabolites are bioactive lipids that are potent, multi-faceted molecules, capable of influencing the activity of CB1, CB2 and TRPV1 receptors.
Bifunctional activation of methane by bioinspired transition metal complexes. A simple methane protease model

Abstract Metal-based bifunctional methane activators are modeled utilizing density functional theory. The impact upon activation barriers of the metal among the late 3d metal MII ions (Co – Zn) is quite pronounced, ca. 7 kcal/mol. Alteration of the metal’s coordination environment without changing the supporting ligand types (e.g., comparing cis and trans coordination isomers) has a computed impact on methane activation barriers of ± 1 kcal/mol. One significant result involves the varying impact of fluorination of the imidazole, which serves as a simple mimic of a histidine side chain. Sequentially fluorinating the 3C–H bonds of imidazole produces a range in the calculated ΔH‡ of 4½ kcal/mol, an effect greater than any other modeled herein apart from the impact of changing the central metal ion of the active site. As such, the present research yields insight into possible avenues for bio-inspired methane activators.
Integrating Machine Learning with HPC-driven Simulations for Enhanced Student Learning

We explore the idea of integrating machine learning (ML) with high performance computing (HPC)-driven simulations to address challenges in using simulations to teach computational science and engineering courses. We demonstrate that a ML surrogate, designed using artificial neural networks, yields predictions in excellent agreement with explicit simulation, but at far less time and computing costs. We develop a web application on nanoHUB that supports both HPC-driven simulation and the ML surrogate methods to produce simulation outputs. This tool is used for both in-classroom instruction and for solving homework problems associated with two courses covering topics in the broad areas of computational materials science, modeling and simulation, and engineering applications of HPC-enabled simulations. The evaluation of the tool via in-classroom student feedback and surveys shows that the ML-enhanced tool provides a dynamic and responsive simulation environment that enhances student learning. The improvement in the interactivity with the simulation framework in terms of real-time engagement and anytime access enables students to develop intuition for the physical system behavior through rapid visualization of variations in output quantities with changes in inputs.
Second Ricci flow on noncompact Hermitian manifolds

In this work, we first establish short time existence and Shi's type estimate of second Ricci flow on complete noncompact Hermitian manifolds. As an application, we use the second Ricci flow to discuss the existence of Kaehler-Einstein metric on complete noncompact Hermitian manifolds.
Small Data Global Well-Posedness for a Boltzmann Equation via Bilinear Spacetime Estimates

We provide a new analysis of the Boltzmann equation with a constant collision kernel in two space dimensions. The scaling-critical Lebesgue space is $$L^2_{x,v}$$ ; we prove the global well-posedness and a version of scattering, assuming that the data $$f_0$$ is sufficiently smooth and localized, and the $$L^2_{x,v}$$ norm of $$f_0$$ is sufficiently small. The proof relies upon a new scaling-critical bilinear spacetime estimate for the collision “gain” term in Boltzmann’s equation, combined with a novel application of the Kaniel–Shinbrot iteration.
Erased: Ending faculty sexual misconduct in academia: An open letter from women of public affairs education

The #MeToo movement is descending upon the walls of the ivory tower. The day of reckoning has come for academia to end teaching staff1 sexual misconduct. As women of public2 and third sector3 educa...
Promoter-specific changes in initiation, elongation, and homeostasis of histone H3 acetylation during CBP/p300 inhibition.

Regulation of RNA Polymerase II (Pol2) elongation in the promoter proximal region is an important and ubiquitous control point for gene expression in metazoans. We report that transcription of the adenovirus 5 E4 region is regulated during the release of paused Pol2 into productive elongation by recruitment of the super elongation complex (SEC), dependent on promoter H3K18/27 acetylation by CBP/p300. We also establish that this is a general transcriptional regulatory mechanism that applies to ~6% of expressed protein-coding genes in primary human airway epithelial cells. We observed that a homeostatic mechanism maintains promoter, but not enhancer H3K18/27ac in response to extensive inhibition of CBP/p300 acetyl transferase activity by the highly specific small molecule inhibitor A-485. Further, our results suggest a function for BRD4 association at enhancers in regulating paused Pol2 release at nearby promoters. Taken together, our results uncover processes regulating transcriptional elongation by promoter region histone H3 acetylation and homeostatic maintenance of promoter, but not enhancer, H3K18/27ac in response to inhibition of CBP/p300 acetyl transferase activity.
Think out of the package: Recommending package types for e-commerce shipments

Manifold of product attributes such as dimensions, weight, fragility and liquid content determine the package type used by e-commerce companies to ship products. Sub-optimal package types lead to damaged shipments, incurring huge damage related costs and adversely impacting the company’s reputation for safe delivery. Items can be shipped in more protective packages to reduce damage costs, however this increases the shipment costs due to expensive packaging and higher transportation costs. In this work, we propose a multi-stage approach that trades-off between shipment and damage costs for each product, and accurately assigns the optimal package type using a scalable, computationally efficient linear time algorithm. A simple binary search algorithm is presented to determine the hyper-parameter that balances between the shipment and damage costs. Our approach when applied to choosing package type for Amazon shipments, leads to significant cost savings of tens of millions of dollars in emerging marketplaces, by decreasing both the overall shipment cost and the number of in-transit damages. Our algorithm is live and deployed in the production system, where package types for more than 130, 000 products have been modified based on the model’s recommendation, realizing a reduction in damage rate of \(24\%\). Overall, the proposed approach has also helped reduce the carbon footprint.
Autonomous Learning of New Environments with a Robotic Team Employing Hyper-Spectral Remote Sensing, Comprehensive In-Situ Sensing and Machine Learning

This paper describes and demonstrates an autonomous robotic team that can rapidly learn the characteristics of environments that it has never seen before. The flexible paradigm is easily scalable to multi-robot, multi-sensor autonomous teams, and it is relevant to satellite calibration/validation and the creation of new remote sensing data products. A case study is described for the rapid characterisation of the aquatic environment, over a period of just a few minutes we acquired thousands of training data points. This training data allowed for our machine learning algorithms to rapidly learn by example and provide wide area maps of the composition of the environment. Along side these larger autonomous robots two smaller robots that can be deployed by a single individual were also deployed (a walking robot and a robotic hover-board), observing significant small scale spatial variability.
The Political Legacy of Violence During China's Cultural Revolution

Autocrats use repression to deter opposition. Are they successful in the long run? The author argues that state repression can have long-lasting alienating effects on citizens’ political attitudes and coercive effects on their political behavior. The article evaluates this proposition by studying the long-term effects of state terror during China's Cultural Revolution. It shows that individuals who grew up in localities that were exposed to more state-sponsored violence in the late 1960s are less trusting of national political leaders and more critical of the country's political system today. These anti-regime attitudes are more likely to be passed down to the younger generation if family members discuss politics frequently than if they do not. Yet while state repression has created anti-regime attitudes, it has decreased citizens’ contentious behavior. These findings highlight the dilemma that authoritarian rulers face when they seek to consolidate their rule through repression.
Parameter Estimation for Mixed-Mechanism Tear Film Thinning.

Etiologies of tear breakup include evaporation-driven, divergent flow-driven, and a combination of these two. A mathematical model incorporating evaporation and lipid-driven tangential flow is fit to fluorescence imaging data. The lipid-driven motion is hypothesized to be caused by localized excess lipid, or “globs.” Tear breakup quantities such as evaporation rates and tangential flow rates cannot currently be directly measured during breakup. We determine such variables by fitting mathematical models for tear breakup and the computed fluorescent intensity to experimental intensity data gathered in vivo. Parameter estimation is conducted via least squares minimization of the difference between experimental data and computed answers using either the trust-region-reflective or Levenberg–Marquardt algorithm. Best-fit determination of tear breakup parameters supports the notion that evaporation and divergent tangential flow can cooperate to drive breakup. The resulting tear breakup is typically faster than purely evaporative cases. Many instances of tear breakup may have similar causes, which suggests that interpretation of experimental results may benefit from considering multiple mechanisms.
Synthesis of low power folded programmable coefficient FIR digital filters

A novel low-power synthesis technique is presented for the design of folded or time-multiplexed programmable-coefficient FIR filters where storage area is traded-off for lowering power consumption. A systematic technique is developed for low power mapping of FIR filters to architectures with arbitrary number of multipliers and adders. Power consumed in multipliers is reduced by reducing switching activity at both the data-in as well as the coefficient input. Common input operands can be exposed unfolding, which, however leads to a memory Increase. Simulation are obtained for folding 65 and 129 tap bandpass FIR filters. The average power consumed in a multiplier for a fixed number of hardware multipliers with varying unfolding factors is compared. It is observed that most of the gains due to unfolding are obtained for relatively small unfolding factors and therefore for relatively small memory area overhead. Depending on the unfolding factor employed the average power consumed in a multiplier is seen to reduce anywhere from 54.75% to 81.73% when transpose FIR filters are synthesized as opposed to synthesizing direct-form FIR filters with no unfolding.
Are You a Boy or a Girl - Show Me Your REAL ID

Although critics have attacked the REAL ID Act on many grounds as an affront to civil liberties, as an unwelcome federal intrusion to a state's police powers, or as the dreaded creation of a national identification card, I argue that the government should remove gender as a required identifier for two additional reasons. First, by barring any state from removing gender or sex from identification cards, the REAL ID Act prevents any state from removing these categories in an effort to reduce the complications of inclusion that a gender identifier inflicts on its gender variant citizens. Second, including a description of gender or sex is not an accurate method of identification, in no small part because gender and sex are not fixed and may later change, so should not be required under a federal law that ostensibly seeks to improve the accuracy of identity cards.This Article first examines the limits of legal classifications that view human traits as dichotomous. Next, it reviews the medical, scientific, and legal problems created by imposing a binary of sex or gender and the resulting problems this creates for many sexual minorities. Finally, this Article examines the REAL ID Act's requirement to include gender, critiquing its inclusion as a poor identifier in light of current identification technology, and a problematic or discriminatory identifier for certain sexual minorities.
A Common Source Input Cross Coupled Quad CMOS Mixer

A CMOS doubly balanced mixer circuit is implemented with a source follower input and a cross coupled mixing quad. The circuit employs an all N-channel configuration and is suitable for high frequency applications. As a down-converter with an RF input of 2.0 GHz and an IF output of 200 MHz, the mixer demonstrates 9 dB of conversion loss with a corresponding input referred third order intercept of 0 dBm. As an up-converter with an IF input frequency of 400 MHz and an RF output of 2.4 GHz, the mixer demonstrates 14 dB of conversion loss.