IIT@MIT

We describe Hi-C, a method that probes the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. We constructed spatial proximity maps of the human genome with Hi-C at a resolution of 1 megabase. These maps confirm the presence of chromosome territories and the spatial proximity of small, gene-rich chromosomes. We identified an additional level of genome organization that is characterized by the spatial segregation of open and closed chromatin to form two genome-wide compartments. At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free, polymer conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus. The fractal globule is distinct from the more commonly used globular equilibrium model. Our results demonstrate the power of Hi-C to map the dynamic conformations of whole genomes.

We investigated the differential diffusion of all of the verified true and false news stories distributed on Twitter from 2006 to 2017. The data comprise ~126,000 stories tweeted by ~3 million people more than 4.5 million times. We classified news as true or false using information from six independent fact-checking organizations that exhibited 95 to 98% agreement on the classifications. Falsehood diffused significantly farther, faster, deeper, and more broadly than the truth in all categories of information, and the effects were more pronounced for false political news than for false news about terrorism, natural disasters, science, urban legends, or financial information. We found that false news was more novel than true news, which suggests that people were more likely to share novel information. Whereas false stories inspired fear, disgust, and surprise in replies, true stories inspired anticipation, sadness, joy, and trust. Contrary to conventional wisdom, robots accelerated the spread of true and false news at the same rate, implying that false news spreads more than the truth because humans, not robots, are more likely to spread it.

Given the central role that software development plays in the delivery and application of information technology, managers are increasingly focusing on process improvement in the software development area. This demand has spurred the provision of a number of new and/or improved approaches to software development, with perhaps the most prominent being object-orientation (OO). In addition, the focus on process improvement has increased the demand for software measures, or metrics with which to manage the process. The need for such metrics is particularly acute when an organization is adopting a new technology for which established practices have yet to be developed. This research addresses these needs through the development and implementation of a new suite of metrics for OO design. Metrics developed in previous research, while contributing to the field's understanding of software development processes, have generally been subject to serious criticisms, including the lack of a theoretical base. Following Wand and Weber (1989), the theoretical base chosen for the metrics was the ontology of Bunge (1977). Six design metrics are developed, and then analytically evaluated against Weyuker's (1988) proposed set of measurement principles. An automated data collection tool was then developed and implemented to collect an empirical sample of these metrics at two field sites in order to demonstrate their feasibility and suggest ways in which managers may use these metrics for process improvement.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>

The dimensionless thermoelectric figure of merit (ZT) in bismuth antimony telluride (BiSbTe) bulk alloys has remained around 1 for more than 50 years. We show that a peak ZT of 1.4 at 100 degrees C can be achieved in a p-type nanocrystalline BiSbTe bulk alloy. These nanocrystalline bulk materials were made by hot pressing nanopowders that were ball-milled from crystalline ingots under inert conditions. Electrical transport measurements, coupled with microstructure studies and modeling, show that the ZT improvement is the result of low thermal conductivity caused by the increased phonon scattering by grain boundaries and defects. More importantly, ZT is about 1.2 at room temperature and 0.8 at 250 degrees C, which makes these materials useful for cooling and power generation. Cooling devices that use these materials have produced high-temperature differences of 86 degrees , 106 degrees , and 119 degrees C with hot-side temperatures set at 50 degrees, 100 degrees, and 150 degrees C, respectively. This discovery sets the stage for use of a new nanocomposite approach in developing high-performance low-cost bulk thermoelectric materials.

To explore the distinct genotypic and phenotypic states of melanoma tumors, we applied single-cell RNA sequencing (RNA-seq) to 4645 single cells isolated from 19 patients, profiling malignant, immune, stromal, and endothelial cells. Malignant cells within the same tumor displayed transcriptional heterogeneity associated with the cell cycle, spatial context, and a drug-resistance program. In particular, all tumors harbored malignant cells from two distinct transcriptional cell states, such that tumors characterized by high levels of the MITF transcription factor also contained cells with low MITF and elevated levels of the AXL kinase. Single-cell analyses suggested distinct tumor microenvironmental patterns, including cell-to-cell interactions. Analysis of tumor-infiltrating T cells revealed exhaustion programs, their connection to T cell activation and clonal expansion, and their variability across patients. Overall, we begin to unravel the cellular ecosystem of tumors and how single-cell genomics offers insights with implications for both targeted and immune therapies.

Hi-C experiments explore the 3D structure of the genome, generating terabases of data to create high-resolution contact maps. Here, we introduce Juicer, an open-source tool for analyzing terabase-scale Hi-C datasets. Juicer allows users without a computational background to transform raw sequence data into normalized contact maps with one click. Juicer produces a hic file containing compressed contact matrices at many resolutions, facilitating visualization and analysis at multiple scales. Structural features, such as loops and domains, are automatically annotated. Juicer is available as open source software at http://aidenlab.org/juicer/.

Identifying interesting relationships between pairs of variables in large data sets is increasingly important. Here, we present a measure of dependence for two-variable relationships: the maximal information coefficient (MIC). MIC captures a wide range of associations both functional and not, and for functional relationships provides a score that roughly equals the coefficient of determination (R(2)) of the data relative to the regression function. MIC belongs to a larger class of maximal information-based nonparametric exploration (MINE) statistics for identifying and classifying relationships. We apply MIC and MINE to data sets in global health, gene expression, major-league baseball, and the human gut microbiota and identify known and novel relationships.

Hi-C for mosquito genomes Most genomes sequenced today are determined through the generation of short sequenced bits of DNA that are computationally pieced together like a jigsaw puzzle. This has resulted in the need for funds and additional data to fill in gaps in order to fully assemble the many chromosomes that make up a eukaryotic genome. Dudchenko et al. used the Hi-C method, which measures the distance between contact points within and between chromosomes for scaffold validation, together with correction and ordering to more completely determine the arrangement of short sequencing reads for genome mapping. They validated their approach through the de novo generation of a complete human genome. A comparative analysis of mosquito genomes was made possible by improving the Culex quinquefasciatus genome assembly and generating the genome of Aedes aegypti , the vector of Zika virus. Science , this issue p. 92

We examine the concerns that new technologies will render labor redundant in a framework in which tasks previously performed by labor can be automated and new versions of existing tasks, in which labor has a comparative advantage, can be created. In a static version where capital is fixed and technology is exogenous, automation reduces employment and the labor share, and may even reduce wages, while the creation of new tasks has the opposite effects. Our full model endogenizes capital accumulation and the direction of research toward automation and the creation of new tasks. If the long-run rental rate of capital relative to the wage is sufficiently low, the long-run equilibrium involves automation of all tasks. Otherwise, there exists a stable balanced growth path in which the two types of innovations go hand-in-hand. Stability is a consequence of the fact that automation reduces the cost of producing using labor, and thus discourages further automation and encourages the creation of new tasks. In an extension with heterogeneous skills, we show that inequality increases during transitions driven both by faster automation and the introduction of new tasks, and characterize the conditions under which inequality stabilizes in the long run. (JEL D63, E22, E23, E24, J24, O33, O41)

11R27. Metal Foams: A Design Guide. - MF Ashby (Eng Dept, Centre for Micromech, Univ of Cambridge, Cambridge, CB2 1PZ, UK), A Evans (Princeton Mat Inst, Princeton Univ, 70 Prospect Ave, Bowen Hall, Princeton NJ 08540), NA Fleck (Eng Dept, Centre for Micromech, Univ of Cambridge, Cambridge, CB2 1PZ, UK), LJ Gibson (Dept of Mat Sci and Eng, MIT, Cambridge, MA), JW Hutchinson (Div of Eng and Appl Sci, Harvard Univ, Oxford St, Cambridge MA 02138), HNG Wadley (Dept of Mat Sci and Eng, Sch of Eng and Appl Sci, Univ of Virginia, Charlottesville VA 22903). Butterworth-Heinemann, Woburn MA. 2000. 251 pp. ISBN 0-7506-7219-6. $75.00. Reviewed by F Delale (Dept of Mech Eng, CCNY, 138th St and Convent Ave, New York NY 10031).Metal foams are a new class of materials with application potential in many areas, especially in the design of lightweight structures. The publication of this book is a timely contribution given the current interest of developing lightweight structures for defense as well as commercial applications. The book is a collaborative effort with contributions from many prominent researchers. It consists of 19 chapters, an Appendix, and an Index. It is a concise treatise in that all this material fits in 251 pages.In the first introductory chapter, metal foams are defined and their potential applications discussed. The next three chapters deal with the making of metal foams, the methods used to characterize them, and the current knowledge about their properties. The authors then proceed to discuss design formulas for simple structures made of metal foams. In the second chapter, a constitutive model for metal foams is presented. The next seven chapters discuss design with metal foams in various applications and under different loading conditions, namely: fatigue, creep, sandwich structures, packaging and blast protection, sound absorption and vibration suppression, and thermal and electrical applications. The cutting, finishing, and joining of foam metals is the subject of the ensuing chapter. In Chapter 17, several case studies are presented. Finally, the book concludes with a listing of metal foam suppliers and of websites related to the subject. As this description indicates, after a brief introduction on the behavior of metal foams, the book is totally dedicated to designing with metal foams. One distinction of this book is that it deals not only with design under mechanical loads, but also with design methodology for other types of loading conditions and phenomena, such as: fatigue, creep, thermal management, sound and vibration, blast protection, etc. The level of mathematics is intentionally kept low to cater to a wider audience. The book is geared toward the practicing engineer, and in that respect, succeeds in fulfilling that goal. Metal Foams: A Design Guide is a worthy addition to the engineering literature, and it is recommended that libraries carry a copy.

Consider three qubits A, B, and C which may be entangled with each other. We show that there is a trade-off between A's entanglement with B and its entanglement with C. This relation is expressed in terms of a measure of entanglement called the concurrence, which is related to the entanglement of formation. Specifically, we show that the squared concurrence between A and B, plus the squared concurrence between A and C, cannot be greater than the squared concurrence between A and the pair BC. This inequality is as strong as it could be, in the sense that for any values of the concurrences satisfying the corresponding equality, one can find a quantum state consistent with those values. Further exploration of this result leads to a definition of an essential three-way entanglement of the system, which is invariant under permutations of the qubits.

The biolinguistic perspective regards the language faculty as an “organ of the body,” along with other cognitive systems. Adopting it, we expect to find three factors that interact to determine (I-) languages attained: genetic endowment (the topic of Universal Grammar), experience, and principles that are language- or even organism-independent. Research has naturally focused on I-languages and UG, the problems of descriptive and explanatory adequacy. The Principles-and-Parameters approach opened the possibility for serious investigation of the third factor, and the attempt to account for properties of language in terms of general considerations of computational efficiency, eliminating some of the technology postulated as specific to language and providing more principled explanation of linguistic phenomena

Rapid detection of nucleic acids is integral for clinical diagnostics and biotechnological applications. We recently developed a platform termed SHERLOCK (specific high-sensitivity enzymatic reporter unlocking) that combines isothermal preamplification with Cas13 to detect single molecules of RNA or DNA. Through characterization of CRISPR enzymology and application development, we report here four advances integrated into SHERLOCK version 2 (SHERLOCKv2) (i) four-channel single-reaction multiplexing with orthogonal CRISPR enzymes; (ii) quantitative measurement of input as low as 2 attomolar; (iii) 3.5-fold increase in signal sensitivity by combining Cas13 with Csm6, an auxiliary CRISPR-associated enzyme; and (iv) lateral-flow readout. SHERLOCKv2 can detect Dengue or Zika virus single-stranded RNA as well as mutations in patient liquid biopsy samples via lateral flow, highlighting its potential as a multiplexable, portable, rapid, and quantitative detection platform of nucleic acids.

Hi-C experiments study how genomes fold in 3D, generating contact maps containing features as small as 20 bp and as large as 200 Mb. Here we introduce Juicebox, a tool for exploring Hi-C and other contact map data. Juicebox allows users to zoom in and out of Hi-C maps interactively, just as a user of Google Earth might zoom in and out of a geographic map. Maps can be compared to one another, or to 1D tracks or 2D feature sets.

Strengthening materials traditionally involves the controlled creation of internal defects and boundaries so as to obstruct dislocation motion. Such strategies invariably compromise ductility, the ability of the material to deform, stretch, or change shape permanently without breaking. Here, we outline an approach to optimize strength and ductility by identifying three essential structural characteristics for boundaries: coherency with surrounding matrix, thermal and mechanical stability, and smallest feature size finer than 100 nanometers. We assess current understanding of strengthening and propose a methodology for engineering coherent, nanoscale internal boundaries, specifically those involving nanoscale twin boundaries. Additionally, we discuss perspectives on strengthening and preserving ductility, along with potential applications for improving failure tolerance, electrical conductivity, and resistance to electromigration.

Clicks is a new software architecture for building flexible and configurable routers. A Click router is assembled from packet processing modules called elements . Individual elements implement simple router functions like packet classification, queuing, scheduling, and interfacing with network devices. A router configurable is a directed graph with elements at the vertices; packets flow along the edges of the graph. Several features make individual elements more powerful and complex configurations easier to write, including pull connections, which model packet flow drivn by transmitting hardware devices, and flow-based router context, which helps an element locate other interesting elements. Click configurations are modular and easy to extend. A standards-compliant Click IP router has 16 elements on its forwarding path; some of its elements are also useful in Ethernet switches and IP tunnelling configurations. Extending the IP router to support dropping policies, fairness among flows, or Differentiated Services simply requires adding a couple of element at the right place. On conventional PC hardware, the Click IP router achieves a maximum loss-free forwarding rate of 333,000 64-byte packets per second, demonstrating that Click's modular and flexible architecture is compatible with good performance.

Nitrogen is fundamental to all of life and many industrial processes. The interchange of nitrogen oxidation states in the industrial production of ammonia, nitric acid, and other commodity chemicals is largely powered by fossil fuels. A key goal of contemporary research in the field of nitrogen chemistry is to minimize the use of fossil fuels by developing more efficient heterogeneous, homogeneous, photo-, and electrocatalytic processes or by adapting the enzymatic processes underlying the natural nitrogen cycle. These approaches, as well as the challenges involved, are discussed in this Review.

We present HiGlass, an open source visualization tool built on web technologies that provides a rich interface for rapid, multiplex, and multiscale navigation of 2D genomic maps alongside 1D genomic tracks, allowing users to combine various data types, synchronize multiple visualization modalities, and share fully customizable views with others. We demonstrate its utility in exploring different experimental conditions, comparing the results of analyses, and creating interactive snapshots to share with collaborators and the broader public. HiGlass is accessible online at http://higlass.io and is also available as a containerized application that can be run on any platform.

A central organizing framework of the voluminous recent literature studying changes in the returns to skills and the evolution of earnings inequality is what we refer to as the canonical model, which elegantly and powerfully operationalizes the supply and demand for skills by assuming two distinct skill groups that perform two different and imperfectly substitutable tasks or produce two imperfectly substitutable goods. Technology is assumed to take a factor-augmenting form, which, by complementing either high or low skill workers, can generate skill biased demand shifts. In this paper, we argue that despite its notable successes, the canonical model is largely silent on a number of central empirical developments of the last three decades, including: (1) significant declines in real wages of low skill workers, particularly low skill males; (2) non-monotone changes in wages at different parts of the earnings distribution during different decades; (3) broad-based increases in employment in high skill and low skill occupations relative to middle skilled occupations (i.e., job 'polarization'); (4) rapid diffusion of new technologies that directly substitute capital for labor in tasks previously performed by moderatelyskilled workers; and (5) expanding offshoring opportunities, enabled by technology, which allow foreign labor to substitute for domestic workers in specific tasks. Motivated by these patterns, we argue that it is valuable to consider a richer framework for analyzing how recent changes in the earnings and employment distribution in the United States and other advanced economies are shaped by the interactions among worker skills, job tasks, evolving technologies, and shifting trading opportunities. We propose a tractable task-based model in which the assignment of skills to tasks is endogenous and technical change may involve the substitution of machines for certain tasks previously performed by labor. We further consider how the evolution of technology in this task-based setting may be endogenized. We show how such a framework can be used to interpret several central recent trends, and we also suggest further directions for empirical exploration.

Topologically associating domains (TADs) are fundamental structural and functional building blocks of human interphase chromosomes, yet the mechanisms of TAD formation remain unclear. Here, we propose that loop extrusion underlies TAD formation. In this process, cis-acting loop-extruding factors, likely cohesins, form progressively larger loops but stall at TAD boundaries due to interactions with boundary proteins, including CTCF. Using polymer simulations, we show that this model produces TADs and finer-scale features of Hi-C data. Each TAD emerges from multiple loops dynamically formed through extrusion, contrary to typical illustrations of single static loops. Loop extrusion both explains diverse experimental observations-including the preferential orientation of CTCF motifs, enrichments of architectural proteins at TAD boundaries, and boundary deletion experiments-and makes specific predictions for the depletion of CTCF versus cohesin. Finally, loop extrusion has potentially far-ranging consequences for processes such as enhancer-promoter interactions, orientation-specific chromosomal looping, and compaction of mitotic chromosomes.