X-ray Evidence for Multiple Absorbing Structures in Seyfert Galaxies

We have used X-ray spectra to measure attenuating columns in a large sample of Seyfert galaxies. Over 30 of these sources have resolved radio jets, allowing the relative orientation of the nucleus and host galaxy to be constrained. We have discovered that the distribution of absorbing columns is strongly correlated with the relative orientation of the Seyfert structures. This result is inconsistent with unification models including only a torus and is instead most readily explained if a second absorber is included: in addition to a Compton-thick, parsec-scale torus there would also be a larger-scale absorber with N_H < 10^{23} cm^{-2}. The second absorber is aligned with the host galactic plane while the torus is arbitrarily misaligned.Comment: 2 pages, 1 figure, to appear in "Multiwavelength AGN Surveys" (Cozumel, December 8-12 2003), ed. R. Maiolino and R. Mujica, Singapore: World Scientific, 2004. Additional material may be found at http://space.mit.edu/home/jonathan/research.htm

Optimal Expectations

This paper introduces a tractable, structural model of subjective beliefs. Since agents that plan for the future care about expected future utility flows, current felicity can be increased by believing that better outcomes are more likely. On the other hand, expectations that are biased towards optimism worsen decision making, leading to poorer realized outcomes on average. Optimal expectations balance these forces by maximizing the total well-being of an agent over time. We apply our framework of optimal expectations to three different economic settings. In a portfolio choice problem, agents overestimate the return of their investment and underdiversify. In general equilibrium, agents' prior beliefs are endogenously heterogeneous, leading to gambling. Second, in a consumption-saving problem with stochastic income, agents are both overconfident and overoptimistic, and consume more than implied by rational beliefs early in life. Third, in choosing when to undertake a single task with an uncertain cost, agents exhibit several features of procrastination, including regret, intertemporal preference reversal, and a greater readiness to accept commitment.expectations formation, beliefs, overconfidence

Optimal Expectations

This paper introduces a tractable, structural model of subjective beliefs. Since agents that plan for the future care about expected future utility flows, current felicity can be increased by believing that better outcomes are more likely. On the other hand, expectations that are biased towards optimism worsen decision making, leading to poorer realized outcomes on average. Optimal expectations balance these forces by maximizing the total well-being of an agent over time. We apply our framework of optimal expectations to three different economic settings. In a portfolio choice problem, agents overestimate the return of their investment and under diversify. In general equilibrium, agents’ prior beliefs are endogenously heterogeneous, leading to gambling. Second, in a consumption-saving problem with stochastic income, agents are both overconfident and overoptimistic, and consume more than implied by rational beliefs early in life. Third, in choosing when to undertake a single task with an uncertain cost, agents exhibit several features of procrastination, including regret, intertemporal preference, reversal, and a greater readiness to accept commitment.Expectations formation, beliefs, overconfidence, wishful thinking, procrastination, gambling

High-resolution mapping of cancer cell networks using co-functional interactions.

Powerful new technologies for perturbing genetic elements have recently expanded the study of genetic interactions in model systems ranging from yeast to human cell lines. However, technical artifacts can confound signal across genetic screens and limit the immense potential of parallel screening approaches. To address this problem, we devised a novel PCA-based method for correcting genome-wide screening data, bolstering the sensitivity and specificity of detection for genetic interactions. Applying this strategy to a set of 436 whole genome CRISPR screens, we report more than 1.5 million pairs of correlated "co-functional" genes that provide finer-scale information about cell compartments, biological pathways, and protein complexes than traditional gene sets. Lastly, we employed a gene community detection approach to implicate core genes for cancer growth and compress signal from functionally related genes in the same community into a single score. This work establishes new algorithms for probing cancer cell networks and motivates the acquisition of further CRISPR screen data across diverse genotypes and cell types to further resolve complex cellular processes

The Functional Consequences of Variation in Transcription Factor Binding

One goal of human genetics is to understand how the information for precise and dynamic gene expression programs is encoded in the genome. The interactions of transcription factors (TFs) with DNA regulatory elements clearly play an important role in determining gene expression outputs, yet the regulatory logic underlying functional transcription factor binding is poorly understood. Many studies have focused on characterizing the genomic locations of TF binding, yet it is unclear to what extent TF binding at any specific locus has functional consequences with respect to gene expression output. To evaluate the context of functional TF binding we knocked down 59 TFs and chromatin modifiers in one HapMap lymphoblastoid cell line. We then identified genes whose expression was affected by the knockdowns. We intersected the gene expression data with transcription factor binding data (based on ChIP-seq and DNase-seq) within 10 kb of the transcription start sites of expressed genes. This combination of data allowed us to infer functional TF binding. On average, 14.7% of genes bound by a factor were differentially expressed following the knockdown of that factor, suggesting that most interactions between TF and chromatin do not result in measurable changes in gene expression levels of putative target genes. We found that functional TF binding is enriched in regulatory elements that harbor a large number of TF binding sites, at sites with predicted higher binding affinity, and at sites that are enriched in genomic regions annotated as active enhancers.Comment: 30 pages, 6 figures (7 supplemental figures and 6 supplemental tables available upon request to [email protected]). Submitted to PLoS Genetic

Structural relaxation in Morse clusters: Energy landscapes

We perform a comprehensive survey of the potential energy landscapes of 13-atom Morse clusters, and describe how they can be characterized and visualized. Our aim is to detail how the global features of the funnel-like surface change with the range of the potential, and to relate these changes to the dynamics of structural relaxation. We find that the landscape becomes rougher and less steep as the range of the potential decreases, and that relaxation paths to the global minimum become more complicated.Comment: 21 pages, 3 tables, 5 figure

Open Letter on Ethical Norms in Intellectual Property Scholarship

As scholars who write in intellectual property (“IP”), we write this letter with aspirations of reaching the highest ethical norms possible for our field. In particular, we have noted an influx of large contributions from corporate and private actors who have an economic stake in ongoing policy debates in the field. Some dollars come with strings attached, such as the ability to see or approve academic work prior to publication or limitations on the release of data. IP scholars who are also engaged in practice or advocacy must struggle to keep their academic and advocacy roles separate.Our goal is to bring attention to the dramatic changes that are occurring in the field, highlight the potential pitfalls, and suggest a set of ethical norms to which we will strive to adhere. We conclude this letter with a set of ethical norms to which a large number of IP academics have already subscribed. We welcome additional signatories to the principles expressed in this letter

Cellular Blood Flow

The fluid dynamics video that is presented here outlines recent advances in the simulation of multiphase cellular blood flow through the direct numerical simulations of deformable red blood cells (RBCs) demonstrated through several numerical experiments. Videos show particle deformation, shear stress on the particle surface, and the formation of particle clusters in both Hagen-Poiseuille and shear flow.Comment: 2 pages, one hyperlink to 2 video

Modelling the Self-Assembly of Virus Capsids

We use computer simulations to study a model, first proposed by Wales [1], for the reversible and monodisperse self-assembly of simple icosahedral virus capsid structures. The success and efficiency of assembly as a function of thermodynamic and geometric factors can be qualitatively related to the potential energy landscape structure of the assembling system. Even though the model is strongly coarse-grained, it exhibits a number of features also observed in experiments, such as sigmoidal assembly dynamics, hysteresis in capsid formation and numerous kinetic traps. We also investigate the effect of macromolecular crowding on the assembly dynamics. Crowding agents generally reduce capsid yields at optimal conditions for non-crowded assembly, but may increase yields for parameter regimes away from the optimum. Finally, we generalize the model to a larger triangulation number T = 3, and observe more complex assembly dynamics than that seen for the original T = 1 model.Comment: 16 pages, 11 figure