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"Rosen, Jonathan"
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From sunset till sunrise
Twelve-year-old cousins Devin and Tommy must survive the night after being invited to a school dance by the pretty new girl in the neighborhood, who happens to be a vampire.
BOOK
Cell-type-specific 3D epigenomes in the developing human cortex
Lineage-specific epigenomic changes during human corticogenesis have been difficult to study owing to challenges with sample availability and tissue heterogeneity. For example, previous studies using single-cell RNA sequencing identified at least 9 major cell types and up to 26 distinct subtypes in the dorsal cortex alone
1
,
2
. Here we characterize cell-type-specific
cis
-regulatory chromatin interactions, open chromatin peaks, and transcriptomes for radial glia, intermediate progenitor cells, excitatory neurons, and interneurons isolated from mid-gestational samples of the human cortex. We show that chromatin interactions underlie several aspects of gene regulation, with transposable elements and disease-associated variants enriched at distal interacting regions in a cell-type-specific manner. In addition, promoters with increased levels of chromatin interactivity—termed super-interactive promoters—are enriched for lineage-specific genes, suggesting that interactions at these loci contribute to the fine-tuning of transcription. Finally, we develop CRISPRview, a technique that integrates immunostaining, CRISPR interference, RNAscope, and image analysis to validate cell-type-specific
cis
-regulatory elements in heterogeneous populations of primary cells. Our findings provide insights into cell-type-specific gene expression patterns in the developing human cortex and advance our understanding of gene regulation and lineage specification during this crucial developmental window.
Analysis of
cis
-regulatory chromatin interactions, open chromatin and transcriptomes for different cell types isolated from mid-gestational human cortex samples provides insights into gene regulation during development.
Journal Article
The best minds : a story of friendship, madness, and the tragedy of good intentions
\"When the Rosens moved to New Rochelle in 1973, Jonathan Rosen and Michael Laudor seemed destined to become inseparable. The boys, both children of college professors, grew up on the same street in intellectually vibrant homes shaped by ideas, liberal Jewish culture, the trauma of the Holocaust, and a shared love of basketball and standup comedy. But the two best friends were also keen competitors bearing the same great expectations, and when Michael and Jonathan both got into Yale, they seemed set to ascend to the heights of the American meritocratic elite. Leaving Jonathan behind, Michael blazed through college in three years, graduating summa cum laude and landing a top-flight consulting job for far more money than their parents had ever made. But all wasn't as it seemed. One day, Jonathan received the fateful call: Michael had suffered a serious psychotic break and was institutionalized at a New York City psychiatric hospital where he was diagnosed with paranoid schizophrenia. He would stay there for nine months before transitioning to a halfway house. Facing the prospect of a life spent bagging groceries, Michael decided to play the one card left to him: just before his break, he had been accepted to Yale Law School, and now, against all odds, he planned to enroll. Still struggling mightily with schizophrenia, Michael made it through the top law school in the country. His extraordinary story soon made the front page of the New York Times; an agent sold his memoir to a major publisher for a large sum; Ron Howard swept in to acquire film rights, with Brad Pitt set to star. It was all a dream come true for Michael and his tirelessly supportive girlfriend Carrie. But then, the unimaginable happened: in the grip of an unshakable paranoid fantasy, Michael stabbed Carrie to death with a kitchen knife. To this day, Michael Laudor remains confined to a maximum-security forensic hospital in upstate New York. The Best Minds is Jonathan Rosen's brilliant and heartbreaking account of what happened to Michael Laudor, and why. Exploring the dramatic transformation of American culture and of society's relationship to mental illness in the second half of the twentieth century, this is a story about the power and limits of the bonds of family, friendship, and community, the lure of the American dream and the promise of academic achievement. At times tender and hilarious, and at times harrowing and almost unbearably sad, The Best Minds is an extreme version of a story that is tragically familiar to all too many. In the hands of a writer of Jonathan Rosen's gifts and dedication, its significance will echo widely\"-- Provided by publisher
Book
Using individual barcodes to increase quantification power of massively parallel reporter assays
Background
Massively parallel reporter assays (MPRAs) are an experimental technology for measuring the activity of thousands of candidate regulatory sequences or their variants in parallel, where the activity of individual sequences is measured from pools of sequence-tagged reporter genes. Activity is derived from the ratio of transcribed RNA to input DNA counts of associated tag sequences in each reporter construct, so-called barcodes. Recently, tools specifically designed to analyze MPRA data were developed that attempt to model the count data, accounting for its inherent variation. Of these tools, MPRAnalyze and mpralm are most widely used. MPRAnalyze models barcode counts to estimate the transcription rate of each sequence. While it has increased statistical power and robustness against outliers compared to mpralm, it is slow and has a high false discovery rate. Mpralm, a tool built on the R package Limma, estimates log fold-changes between different sequences. As opposed to MPRAnalyze, it is fast and has a low false discovery rate but is susceptible to outliers and has less statistical power.
Results
We propose BCalm, an MPRA analysis framework aimed at addressing the limitations of the existing tools. BCalm is an adaptation of mpralm, but models individual barcode counts instead of aggregating counts per sequence. Leaving out the aggregation step increases statistical power and improves robustness to outliers, while being fast and precise. We show the improved performance over existing methods on both simulated MPRA data and a lentiviral MPRA library of 166,508 target sequences, including 82,258 allelic variants. Further, BCalm adds functionality beyond the existing mpralm package, such as preparing count input files from MPRAsnakeflow, as well as an option to test for sequences with enhancing or repressing activity. Its built-in plotting functionalities allow for easy interpretation of the results.
Conclusions
With BCalm, we provide a new tool for analyzing MPRA data which is robust and accurate on real MPRA datasets. The package is available at
https://github.com/kircherlab/BCalm
.
Journal Article
Highly porous non-precious bimetallic electrocatalysts for efficient hydrogen evolution
A robust and efficient non-precious metal catalyst for hydrogen evolution reaction is one of the key components for carbon dioxide-free hydrogen production. Here we report that a hierarchical nanoporous copper-titanium bimetallic electrocatalyst is able to produce hydrogen from water under a mild overpotential at more than twice the rate of state-of-the-art carbon-supported platinum catalyst. Although both copper and titanium are known to be poor hydrogen evolution catalysts, the combination of these two elements creates unique copper-copper-titanium hollow sites, which have a hydrogen-binding energy very similar to that of platinum, resulting in an exceptional hydrogen evolution activity. In addition, the hierarchical porosity of the nanoporous copper-titanium catalyst also contributes to its high hydrogen evolution activity, because it provides a large-surface area for electrocatalytic hydrogen evolution, and improves the mass transport properties. Moreover, the catalyst is self-supported, eliminating the overpotential associated with the catalyst/support interface.
Investigations into non-precious metal catalysts for hydrogen evolution are ongoing. Here, the authors report a hierarchical, nanoporous copper-titanium electrocatalyst, and demonstrate that it catalyses hydrogen production at twice the over-all rate of commercial platinum-based catalysts.
Journal Article
Illicit markets, organized crime, and global security
This text explains the existence of illicit markets throughout human history and provides recommendations to governments. Organized criminal networks increased in strength after the enforcement of prohibition, eventually challenging the authority of the state and its institutions through corruption and violence. Criminal networks now organize under cyber-infrastructure, what we call the Deep or Dark Web. The authors analyze how illicit markets come together, issues of destabilization and international security, the effect of legitimate enterprises crowded out of developing countries, and ultimately, illicit markets' cost to human life.
Book
Understanding support for Mano Dura strategies: Lessons from Brazil and Colombia
There are many scholarly works focusing on organized crime and violence in Latin America. Scholars have shown empirically that tough on crime strategies have had collateral damages and have not been effective. By conducting logistic regression models using individual country survey data, this work seeks to analyze why tough on crime policies remain popular in some Latin American countries despite the decades of research criticizing these strategies. This article explores the cases of Colombia and Brazil, which have long histories of gang activity, organized crime, and violence. These countries also have elected presidential candidates who campaigned on iron fist strategies.
Journal Article