Inferring HIV escape rates from multi-locus genotype data

Cytotoxic T-lymphocytes (CTLs) recognize viral protein fragments displayed by major histocompatibility complex (MHC) molecules on the surface of virally infected cells and generate an anti-viral response that can kill the infected cells. Virus variants whose protein fragments are not efficiently presented on infected cells or whose fragments are presented but not recognized by CTLs therefore have a competitive advantage and spread rapidly through the population. We present a method that allows a more robust estimation of these escape rates from serially sampled sequence data. The proposed method accounts for competition between multiple escapes by explicitly modeling the accumulation of escape mutations and the stochastic effects of rare multiple mutants. Applying our method to serially sampled HIV sequence data, we estimate rates of HIV escape that are substantially larger than those previously reported. The method can be extended to complex escapes that require compensatory mutations. We expect our method to be applicable in other contexts such as cancer evolution where time series data is also available

The Smuggling Career of William King

This article discusses the activities of William King during the War of 1812. It describes that the war did not stop Anglo-American trade but forced it into semi-legal channels. The article was the 1977 Maine Historical Society Prize Essay

Stuck on Gold: Real Exchange Rate Volatility and the Rise and Fall of the Gold Standard

Did adoption of the gold standard exacerbate or diminish macroeconomic volatility? Supporters thought so, critics thought not, and theory offers ambiguous messages. A hard exchange-rate regime such as the gold standard might limit monetary shocks if it ties the hands of policy makers. But any decision to forsake exchange-rate flexibility might compromise shock absorption in a world of real shocks and nominal stickiness. A simple model shows how a lack of flexibility can be discerned in the transmission of terms of trade shocks. Evidence on the relationship between real exchange rate volatility and terms of trade volatility from the late nineteenth and early twentieth century exposes a dramatic change. The classical gold standard did absorb shocks, but the interwar gold standard did not, and this historical pattern suggests that the interwar gold standard was a poor regime choice.

Trade, Knowledge, and the Industrial Revolution

Technological change was unskilled-labor-biased during the early Industrial Revolution of the late eighteenth and early nineteenth centuries, but is skill-biased today. This fact is not embedded in extant unified growth models. We develop a model of the transition to sustained economic growth which can endogenously account for both these facts, by allowing the factor bias of technological innovations to reflect the profit-maximising decisions of innovators. Endowments dictated that the initial stages of the Industrial Revolution be unskilled-labor biased. The transition to skill-biased technological change was due to a growth in "Baconian knowledge" and international trade. Simulations show that the model does a good job of tracking reality, at least until the mass education reforms of the late nineteenth century.

Trade, Technology and the Great Divergence

This paper develops a model that captures the key features of the Industrial Revolution and the Great Divergence between the industrializing \North" and the lagging \South." In particular, a convincing story is needed for why North-South divergence occurred so dramatically during the late 19th Century, a good hundred years after the beginnings of the Industrial Revolution. To this end we construct a trade/growth model that includes both endogenous biased technologies and intercontinental trade. The Industrial Revolution began as a sequence of unskilled-labor intensive innovations which initially incited fertil- ity increases and limited human capital formation in both the North and the South. The subsequent co-evolution of trade and technological growth however fostered an inevitable di- vergence in living standards - the South increasingly specialized in production that worsened their terms of trade and spurred even greater fertility increases and educational declines. Biased technological changes in both regions only reinforced this pattern. The model high- lights how pronounced divergence ultimately arose from interactions between specialization from trade and technological forces.

Trade, Knowledge, and the Industrial Revolution

Technological change was unskilled-labor-biased during the early Industrial Revolution of the late eighteenth and early nineteenth centuries, but is skill-biased today. This fact is not embedded in extant unified growth models. We develop a model of the transition to sustained economic growth which can endogenously account for both these facts, by allowing the factor bias of technological innovations to reflect the profitmaximising decisions of innovators. Endowments dictated that the initial stages of the Industrial Revolution be unskilled-labor biased. The transition to skill-biased technological change was due to a growth in “Baconian knowledge” and international trade. Simulations show that the model does a good job of tracking reality, at least until the mass education reforms of the late nineteenth century.Endogenous growth, Demography, Trade

Luddites and the Demographic Transition

Technological change was unskilled-labor-biased during the early Industrial Revolution, but is skill-biased today. This is not embedded in extant unified growth models. We develop a model which can endogenously account for these facts, where factor bias reflects profit-maximizing decisions by innovators. Endowments dictate that the early Industrial Revolution be unskilled-labor-biased. Increasing basic knowledge causes a growth takeoff, an income-led demand for fewer educated children, and the transition to skill-biased technological change. The simulated model tracks British industrialization in the 18th and 19th centuries and generates a demographic transition without relying on either rising skill premia or exogenous educational supply shocks.

CONTEST : a Controllable Test Matrix Toolbox for MATLAB

Large, sparse networks that describe complex interactions are a common feature across a number of disciplines, giving rise to many challenging matrix computational tasks. Several random graph models have been proposed that capture key properties of real-life networks. These models provide realistic, parametrized matrices for testing linear system and eigenvalue solvers. CONTEST (CONtrollable TEST matrices) is a random network toolbox for MATLAB that implements nine models. The models produce unweighted directed or undirected graphs; that is, symmetric or unsymmetric matrices with elements equal to zero or one. They have one or more parameters that affect features such as sparsity and characteristic pathlength and all can be of arbitrary dimension. Utility functions are supplied for rewiring, adding extra shortcuts and subsampling in order to create further classes of networks. Other utilities convert the adjacency matrices into real-valued coefficient matrices for naturally arising computational tasks that reduce to sparse linear system and eigenvalue problems

Prenatal factors contribute to the emergence of kwoshiorkor or marasmus in severe undernutrition: evidence for the predictive adaptation model

Severe acute malnutrition in childhood manifests as oedematous (kwashiorkor, marasmic kwashiorkor) and non-oedematous (marasmus) syndromes with very different prognoses. Kwashiorkor differs from marasmus in the patterns of protein, amino acid and lipid metabolism when patients are acutely ill as well as after rehabilitation to ideal weight for height. Metabolic patterns among marasmic patients define them as metabolically thrifty, while kwashiorkor patients function as metabolically profligate. Such differences might underlie syndromic presentation and prognosis. However, no fundamental explanation exists for these differences in metabolism, nor clinical pictures, given similar exposures to undernutrition. We hypothesized that different developmental trajectories underlie these clinical-metabolic phenotypes: if so this would be strong evidence in support of predictive adaptation model of developmental plasticity

A Moving-Knife Solution to the Four-Person Envy-Free Cake-Division Problem

Envy-freeness