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MIT Open Access Articles

Mostrando recursos 1 - 20 de 11.071

1. Holographic Schwinger Effect and the Geometry of Entanglement - Sonner, Julian
We show that the recently proposed bulk dual of an entangled pair of a quark and an antiquark corresponds to the Lorentzian continuation of the tunneling instanton describing Schwinger pair creation in the dual field theory. This observation supports and further explains the claim by Jensen and Karch that the bulk dual of an Einstein-Podolsky-Rosen pair is a string with a wormhole on its world sheet. We suggest that this constitutes a holographically dual realization of the creation of a Wheeler wormhole.

2. Emergent Honeycomb Lattice in LiZn[subscript 2]Mo[subscript 3]O[subscript 8] - Flint, Rebecca; Lee, Patrick A.
We introduce the idea of emergent lattices, where a simple lattice decouples into two weakly coupled lattices as a way to stabilize spin liquids. In LiZn[subscript 2]Mo[subscript 3]O[subscript 8], the disappearance of 2/3 of the spins at low temperatures suggests that its triangular lattice decouples into an emergent honeycomb lattice weakly coupled to the remaining spins, and we suggest several ways to test this proposal. We show that these orphan spins act to stabilize the spin liquid in the J[subscript 1]-J[subscript 2] honeycomb model and also discuss a possible 3D analogue, Ba[subscript 2]MoYO[subscript 6] that may form a “depleted fcc...

3. New Probe of Naturalness - Craig, Nathaniel; Englert, Christoph; McCullough, Matthew Philip
Any new scalar fields that perturbatively solve the hierarchy problem by stabilizing the Higgs boson mass also generate new contributions to the Higgs boson field-strength renormalization, irrespective of their gauge representation. These new contributions are physical, and in explicit models their magnitude can be inferred from the requirement of quadratic divergence cancellation; hence, they are directly related to the resolution of the hierarchy problem. Upon canonically normalizing the Higgs field, these new contributions lead to modifications of Higgs couplings that are typically great enough that the hierarchy problem and the concept of electroweak naturalness can be probed thoroughly within a...

4. Direct Observation of Rapid Discrete Spectral Dynamics in Single Colloidal CdSe-CdS Core-Shell Quantum Dots - Marshall, Lisa F.; Cui, Jian; Brokmann, Xavier; Bawendi, Moungi G.; Beyler, Andrew Paul
We measure the anomalous spectral diffusion of single colloidal quantum dots over eight temporal decades simultaneously by combining single-molecule spectroscopy and photon-correlation Fourier spectroscopy. Our technique distinguishes between discrete and continuous dynamics and directly reveals that the quasicontinuous spectral diffusion observed using conventional spectroscopy is composed of rapid, discrete spectral jumps. Despite their multiple time scales, these dynamics can be captured by a single mechanism whose parameters vary widely between dots and over time in individual dots.

5. Cosmic Evolution from Phase Transition of Three-Dimensional Flat Space - Bagchi, Arjun; Detournay, Stephane; Grumiller, Daniel; Simon, Joan
Flat space cosmology spacetimes are exact time-dependent solutions of three-dimensional gravity theories, such as Einstein gravity or topologically massive gravity. We exhibit a novel kind of phase transition between these cosmological spacetimes and the Minkowski vacuum. At sufficiently high temperature, (rotating) hot flat space tunnels into a universe described by flat space cosmology.

6. Evolutionary principles of modular gene regulation in yeasts - Thompson, Dawn A.; Roy, Sushmita; Chan, Michelle Mei Wah; Styczynsky, Mark P.; Pfiffner, Jenna; French, Courtney; Socha, Amanda; Thielke, Anne; Napolitano, Sara; Muller, Paul; Kellis, Manolis; Konieczka, Jay H.; Wapinski, Ilan; Regev, Aviv
Divergence in gene regulation can play a major role in evolution. Here, we used a phylogenetic framework to measure mRNA profiles in 15 yeast species from the phylum Ascomycota and reconstruct the evolution of their modular regulatory programs along a time course of growth on glucose over 300 million years. We found that modules have diverged proportionally to phylogenetic distance, with prominent changes in gene regulation accompanying changes in lifestyle and ploidy, especially in carbon metabolism. Paralogs have significantly contributed to regulatory divergence, typically within a very short window from their duplication. Paralogs from a whole genome duplication (WGD) event...

7. Arboretum: Reconstruction and analysis of the evolutionary history of condition-specific transcriptional modules - Kellis, Manolis; Regev, Aviv; Roy, Sushmita; Wapinski, Ilan; Pfiffner, Jenna; French, Courtney; Socha, Amanda; Konieczka, Jay; Habib, Naomi; Thompson, Dawn
Comparative functional genomics studies the evolution of biological processes by analyzing functional data, such as gene expression profiles, across species. A major challenge is to compare profiles collected in a complex phylogeny. Here, we present Arboretum, a novel scalable computational algorithm that integrates expression data from multiple species with species and gene phylogenies to infer modules of coexpressed genes in extant species and their evolutionary histories. We also develop new, generally applicable measures of conservation and divergence in gene regulatory modules to assess the impact of changes in gene content and expression on module evolution. We used Arboretum to study...

8. Comparative analysis of RNA sequencing methods for degraded or low-input samples - Adiconis, Xian; Borges-Rivera, Diego; Satija, Rahul; DeLuca, David S; Busby, Michele A; Berlin, Aaron M; Sivachenko, Andrey; Thompson, Dawn Anne; Wysoker, Alec; Fennell, Timothy; Gnirke, Andreas; Pochet, Nathalie; Regev, Aviv; Levin, Joshua Z
RNA-seq is an effective method for studying the transcriptome, but it can be difficult to apply to scarce or degraded RNA from fixed clinical samples, rare cell populations or cadavers. Recent studies have proposed several methods for RNA-seq of low-quality and/or low-quantity samples, but the relative merits of these methods have not been systematically analyzed. Here we compare five such methods using metrics relevant to transcriptome annotation, transcript discovery and gene expression. Using a single human RNA sample, we constructed and sequenced ten libraries with these methods and compared them against two control libraries. We found that the RNase H...

9. Transcriptional Regulatory Circuits: Predicting Numbers from Alphabets - Kim, Harold D.; Shay, Tal; O'Shea, Erin K.; Regev, Aviv
Transcriptional regulatory circuits govern how cis and trans factors transform signals into messenger RNA (mRNA) expression levels. With advances in quantitative and high-throughput technologies that allow measurement of gene expression state in different conditions, data that can be used to build and test models of transcriptional regulation is being generated at a rapid pace. Here, we review experimental and computational methods used to derive detailed quantitative circuit models on a small scale and cruder, genome-wide models on a large scale. We discuss the potential of combining small- and large-scale approaches to understand the working and wiring of transcriptional regulatory circuits.

10. Intact sphingomyelin biosynthetic pathway is essential for intracellular transport of influenza virus glycoproteins - Ploegh, Hidde; Tafesse, Fikadu G.; Sanyal, Sumana; Ashour, Joseph; Guimaraes, Carla P.; Hermansson, Martin; Somerharju, Pentti
Cells genetically deficient in sphingomyelin synthase-1 (SGMS1) or blocked in their synthesis pharmacologically through exposure to a serine palmitoyltransferase inhibitor (myriocin) show strongly reduced surface display of influenza virus glycoproteins hemagglutinin (HA) and neuraminidase (NA). The transport of HA to the cell surface was assessed by accessibility of HA on intact cells to exogenously added trypsin and to HA-specific antibodies. Rates of de novo synthesis of viral proteins in wild-type and SGMS1-deficient cells were equivalent, and HA negotiated the intracellular trafficking pathway through the Golgi normally. We engineered a strain of influenza virus to allow site-specific labeling of HA and...

11. Intercellular trafficking of the nuclear oncoprotein DEK - Ploegh, Hidde; Saha, Anjan K.; Kappes, Ferdinand; Mundade, Amruta; Deutzmann, Anja; Rosmarin, David M.; Legendre, Maureen; Chatain, Nicolas; Al-Obaidi, Zeina; Adams, Barbara S.; Ferrando-May, Elisa; Mor-Vaknin, Nirit; Markovitz, David M.
DEK is a biochemically distinct, conserved nonhistone protein that is vital to global heterochromatin integrity. In addition, DEK can be secreted and function as a chemotactic, proinflammatory factor. Here we show that exogenous DEK can penetrate cells, translocate to the nucleus, and there carry out its endogenous nuclear functions. Strikingly, adjacent cells can take up DEK secreted from synovial macrophages. DEK internalization is a heparan sulfate-dependent process, and cellular uptake of DEK into DEK knockdown cells corrects global heterochromatin depletion and DNA repair deficits, the phenotypic aberrations characteristic of these cells. These findings thus unify the extracellular and intracellular activities...

12. “Friday off”: Reducing Working Hours in Europe - Kallis, Giorgos; Kalush, Michael; O.'Flynn, Hugh; Rossiter, Jack; Ashford, Nicholas A.
This article explores the pros and cons for reducing working hours in Europe. To arrive to an informed judgment we review critically the theoretical and empirical literature, mostly from economics, concerning the relation between working hours on the one hand, and productivity, employment, quality of life, and the environment, on the other. We adopt a binary economics distinction between capital and labor productiveness, and are concerned with how working hours may be reduced without harming the earning capacity of workers. There are reasons to believe that reducing working hours may absorb some unemployment, especially in the short-run, even if less...

13. Drosophila Embryonic Cell-Cycle Mutants - Unhavaithaya, Yingdee; Park, Eugenia A.; Royzman, Irena; Orr-Weaver, Terry L.
Nearly all cell division mutants in Drosophila were recovered in late larval/pupal lethal screens, with less than 10 embryonic lethal mutants identified, because larval development occurs without a requirement for cell division. Only cells in the nervous system and the imaginal cells that generate the adult body divide during larval stages, with larval tissues growing by increasing ploidy rather than cell number. Thus, most mutants perturbing mitosis or the cell cycle do not manifest a phenotype until the adult body differentiates in late larval and pupal stages. To identify cell-cycle components whose maternal pools are depleted in embryogenesis or that...

14. Fundamental differences in endoreplication in mammals and Drosophila revealed by analysis of endocycling and endomitotic cells - Orr-Weaver, Terry L.; Sher, Noa; Von Stetina, Jessica R.; Bell, George W.; Matsuura, Shinobu; Ravid, Katya
Throughout the plant and animal kingdoms specific cell types become polyploid, increasing their DNA content to attain a large cell size. In mammals, megakaryocytes (MKs) become polyploid before fragmenting into platelets. The mammalian trophoblast giant cells (TGCs) exploit their size to form a barrier between the maternal and embryonic tissues. The mechanism of polyploidization has been investigated extensively in Drosophila, in which a modified cell cycle—the endocycle, consisting solely of alternating S and gap phases—produces polyploid tissues. During S phase in the Drosophila endocycle, heterochromatin and specific euchromatic regions are underreplicated and reduced in copy number. Here we investigate the...

15. Polyploidization of glia in neural development links tissue growth to blood-brain barrier integrity - Orr-Weaver, Terry L.; Unhavaithaya, Yingdee
Proper development requires coordination in growth of the cell types composing an organ. Many plant and animal cells are polyploid, but how these polyploid tissues contribute to organ growth is not well understood. We found the Drosophila melanogaster subperineurial glia (SPG) to be polyploid, and ploidy is coordinated with brain mass. Inhibition of SPG polyploidy caused rupture of the septate junctions necessary for the blood–brain barrier. Thus, the increased SPG cell size resulting from polyploidization is required to maintain the SPG envelope surrounding the growing brain. Polyploidization likely is a conserved strategy to coordinate tissue growth during organogenesis, with potential...

16. Integrative analysis of gene amplification in Drosophila follicle cells: parameters of origin activation and repression - Kim, Jane C.; Nordman, Jared; Xie, Fang; Orr-Weaver, Terry L.; Kashevsky, Helena; Eng, Thomas; Li, Sharon; MacAlpine, David M.
In metazoans, how replication origins are specified and subsequently activated is not well understood. Drosophila amplicons in follicle cells (DAFCs) are genomic regions that undergo rereplication to increase DNA copy number. We identified all DAFCs by comparative genomic hybridization, uncovering two new amplicons in addition to four known previously. The complete identification of all DAFCs enabled us to investigate these in vivo replicons with respect to parameters of transcription, localization of the origin recognition complex (ORC), and histone acetylation, yielding important insights into gene amplification as a metazoan replication model. Significantly, ORC is bound across domains spanning 10 or more...

17. Regulated ADAM17-dependent EGF family ligand release by substrate-selecting signaling pathways - Dang, Michelle; Armbruster, Nicole; Miller, Miles Aaron; Cermeno, Efrain A.; Hartmann, Monika; Bell, George W.; Root, David E.; Lauffenburger, Douglas A.; Lodish, Harvey F.; Herrlich, Andreas
Ectodomain cleavage of cell-surface proteins by A disintegrin and metalloproteinases (ADAMs) is highly regulated, and its dysregulation has been linked to many diseases. ADAM10 and ADAM17 cleave most disease-relevant substrates. Broad-spectrum metalloprotease inhibitors have failed clinically, and targeting the cleavage of a specific substrate has remained impossible. It is therefore necessary to identify signaling intermediates that determine substrate specificity of cleavage. We show here that phorbol ester or angiotensin II-induced proteolytic release of EGF family members may not require a significant increase in ADAM17 protease activity. Rather, inducers activate a signaling pathway using PKC-α and the PKC-regulated protein phosphatase 1...

18. Zfp36l2 is required for self-renewal of early erythroid BFU-E progenitors - Zhang, Lingbo; Prak, Lina; Rayon-Estrada, Violeta; Thiru, Prathapan; Flygare, Johan; Lim, Bing; Lodish, Harvey F.
Stem cells and progenitors in many lineages undergo self-renewing divisions, but the extracellular and intracellular proteins that regulate this process are largely unknown. Glucocorticoids stimulate red blood cell formation by promoting self-renewal of early burst-forming unit–erythroid (BFU–E) progenitors. Here we show that the RNA-binding protein ZFP36L2 is a transcriptional target of the glucocorticoid receptor (GR) in BFU–Es and is required for BFU–E self-renewal. ZFP36L2 is normally downregulated during erythroid differentiation from the BFU–E stage, but its expression is maintained by all tested GR agonists that stimulate BFU–E self-renewal, and the GR binds to several potential enhancer regions of ZFP36L2. Knockdown...

19. Whose Mass is it Anyway? Particle Cosmology and the Objects of Theory - Kaiser, David I.
Physicists in different branches of the discipline were puzzled by the problem of mass during the 1950s and 1960s: why do objects have mass? Around the same time, yet working independently, specialists in gravitational studies and in particle theory proposed that mass might arise due to objects’ interactions with a new (and as yet undetected) field. Although the questions they posed and even the answers they provided shared several similarities - and even though both proposals quickly became ‘hot topics’ in their respective subfields - virtually no one discussed one proposal in the light of the other for nearly 20...

20. Differential regulation of synchronous versus asynchronous neurotransmitter release by the C2 domains of synaptotagmin 1 - Yoshihara, Motojiro; Guan, Zhuo; Littleton, J. Troy
Synaptic vesicle fusion at many synapses has been kinetically separated into two distinct Ca[superscript 2+]-dependent temporal components consisting of a rapid synchronous phase followed by a slower asynchronous component. Mutations in the synaptic vesicle Ca[superscript 2+] sensor Synaptotagmin 1 (Syt 1) reduce synchronous neurotransmission while enhancing the slower asynchronous phase of release. Syt 1 regulation of vesicle fusion requires interactions mediated by its tandem cytoplasmic C2 domains (C2A and C2B). Although Ca[superscript 2+] binding by Syt 1 is predicted to drive synchronous release, it is unknown if Ca[superscript 2+] interactions with either C2 domain is required for suppression of asynchronous...

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