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MIT Open Access Articles

Mostrando recursos 41 - 60 de 22.163

  1. Audio-band coating thermal noise measurement for Advanced LIGO with a multimode optical resonator

    Gras, Slawomir; Yu, H.; Yam, William; Martynov, Denis; Evans, Matthew J
    In modern high precision optical instruments, such as in gravitational wave detectors or frequency references, thermally induced fluctuations in the reflective coatings can be a limiting noise source. This noise, known as coating thermal noise, can be reduced by choosing materials with low mechanical loss. Examination of new materials becomes a necessity in order to further minimize the coating thermal noise and thus improve sensitivity of next generation instruments. We present a novel approach to directly measure coating thermal noise using a high finesse folded cavity in which multiple Hermite-Gaussian modes coresonate. This method is used to probe surface fluctuations...

  2. High-throughput functional comparison of promoter and enhancer activities

    Nguyen, Thomas A.; Jones, Richard D.; Snavely, Andrew R.; Kirchner, Rory; Hemberg, Martin; Gray, Jesse M.; Pfenning, Andreas R.
    Promoters initiate RNA synthesis, and enhancers stimulate promoter activity. Whether promoter and enhancer activities are encoded distinctly in DNA sequences is unknown. We measured the enhancer and promoter activities of thousands of DNA fragments transduced into mouse neurons. We focused on genomic loci bound by the neuronal activity-regulated coactivator CREBBP, and we measured enhancer and promoter activities both before and after neuronal activation. We find that the same sequences typically encode both enhancer and promoter activities. However, gene promoters generate more promoter activity than distal enhancers, despite generating similar enhancer activity. Surprisingly, the greater promoter activity of gene promoters is...

  3. High sensitivity of Indian summer monsoon to Middle East dust absorptive properties

    Yang, Zong-Liang; Wei, Jiangfeng; Jin, Qinjian
    The absorptive properties of dust aerosols largely determine the magnitude of their radiative impacts on the climate system. Currently, climate models use globally constant values of dust imaginary refractive index (IRI), a parameter describing the dust absorption efficiency of solar radiation, although it is highly variable. Here we show with model experiments that the dust-induced Indian summer monsoon (ISM) rainfall differences (with dust minus without dust) change from −9% to 23% of long-term climatology as the dust IRI is changed from zero to the highest values used in the current literature. A comparison of the model results with surface observations,...

  4. Chemoenzymatic Assembly of Bacterial Glycoconjugates for Site-Specific Orthogonal Labeling

    Guan, Ziqiang; Lukose, Vinita; Whitworth, Garrett; Imperiali, Barbara
    The cell surfaces of bacteria are replete with diverse glycoconjugates that play pivotal roles in determining how bacteria interact with the environment and the hosts that they colonize. Studies to advance our understanding of these interactions rely on the availability of chemically defined glycoconjugates that can be selectively modified under orthogonal reaction conditions to serve as discrete ligands to probe biological interactions, in displayed arrays and as imaging agents. Herein, enzymes in the N-linked protein glycosylation (Pgl) pathway of Campylobacter jejuni are evaluated for their tolerance for azide-modified UDP-sugar substrates, including derivatives of 2,4-diacetamidobacillosamine and N-acetylgalactosamine. In vitro analyses reveal that chemoenzymatic...

  5. Polo-like Kinase 1 Licenses CENP-A Deposition at Centromeres

    McKinley, Kara Lavidge; Cheeseman, Iain M
    To ensure the stable transmission of the genome during vertebrate cell division, the mitotic spindle must attach to a single locus on each chromosome, termed the centromere. The fundamental requirement for faithful centromere inheritance is the controlled deposition of the centromere-specifying histone, CENP-A. However, the regulatory mechanisms that ensure the precise control of CENP-A deposition have proven elusive. Here, we identify polo-like kinase 1 (Plk1) as a centromere-localized regulator required to initiate CENP-A deposition in human cells. We demonstrate that faithful CENP-A deposition requires integrated signals from Plk1 and cyclin-dependent kinase (CDK), with Plk1 promoting the localization of the key...

  6. Apollonian structure in the Abelian sandpile

    Levine, Lionel; Pegden, Wesley; Smart, Charles
    The Abelian sandpile process evolves configurations of chips on the integer lattice by toppling any vertex with at least 4 chips, distributing one of its chips to each of its 4 neighbors. When begun from a large stack of chips, the terminal state of the sandpile has a curious fractal structure which has remained unexplained. Using a characterization of the quadratic growths attainable by integer-superharmonic functions, we prove that the sandpile PDE recently shown to characterize the scaling limit of the sandpile admits certain fractal solutions, giving a precise mathematical perspective on the fractal nature of the sandpile.

  7. The equivariant pair-of-pants product in fixed point Floer cohomology

    Seidel, Paul Alfred
    We use equivariant methods and product structures to derive a relation between the fixed point Floer cohomology of an exact symplectic automorphism and that of its square.

  8. Predicting distributional restrictions on prenasalized stops

    Stanton, Juliet
    Previous studies on prenasalized stops (NCs) focus mainly on issues of derivation and classification, but little is known about their distributional properties. The current study fills this gap. I present results of a survey documenting positional restrictions on NCs, and show that there are predictable and systematic constraints on their distribution. The major finding is that NCs are optimally licensed in contexts where they are perceptually distinct from plain oral and nasal stops. I provide an analysis referencing auditory factors, and show that a perceptual account explains all attested patterns.

  9. Evaluating discrete choice prediction models when the evaluation data is corrupted: analytic results and bias corrections for the area under the ROC

    Stein, Roger Mark
    There has been a growing recognition that issues of data quality, which are routine in practice, can materially affect the assessment of learned model performance. In this paper, we develop some analytic results that are useful in sizing the biases associated with tests of discriminatory model power when these are performed using corrupt (“noisy”) data. As it is sometimes unavoidable to test models with data that are known to be corrupt, we also provide some guidance on interpreting results of such tests. In some cases, with appropriate knowledge of the corruption mechanism, the true values of the performance statistics such...

  10. SUN Database: Exploring a Large Collection of Scene Categories

    Xiao, Jianxiong; Hays, James; Torralba, Antonio; Ehinger, Krista A.; Oliva, Aude
    Progress in scene understanding requires reasoning about the rich and diverse visual environments that make up our daily experience. To this end, we propose the Scene Understanding database, a nearly exhaustive collection of scenes categorized at the same level of specificity as human discourse. The database contains 908 distinct scene categories and 131,072 images. Given this data with both scene and object labels available, we perform in-depth analysis of co-occurrence statistics and the contextual relationship. To better understand this large scale taxonomy of scene categories, we perform two human experiments: we quantify human scene recognition accuracy, and we measure how...

  11. Inactivation of Bacteria by Electric Current in the Presence of Carbon Nanotubes Embedded Within a Polymeric Membrane

    Long, Feng; Zhu, Anna; Su, Erzheng; Liu, Harris K.; Klibanov, Alexander M
    Uniform conductive composite membranes were prepared using a phase inversion method by blending carboxyl-functionalized multi-walled carbon nanotubes (CNTs) with a polysulfone polymer. At 6 % of the embedded CNTs, the membrane pore size measured by transmission electron microscopy (TEM) was approximately 50 nm. Electric current in the presence of the composite membranes markedly inactivated the model pathogenic bacteria Escherichia coli and Staphylococcus aureus, with the extent of bacterial inactivation rising when the current was increased. Over 99.999 % inactivation of both bacteria was observed in deionized water after 40 min at 5 mA direct current (DC); importantly, no appreciable inactivation...

  12. Simple Expressions for the Design of Linear Tapers in Overmoded Corrugated Waveguides

    Schaub, Samuel Clay; Shapiro, Michael; Temkin, Richard J
    Simple analytical formulae are presented for the design of linear tapers with very low mode conversion loss in overmoded corrugated waveguides. For tapers from waveguide radius a[subscript 2] to a[subscript 1], with a[subscript 1]

  13. SIRT1 Mediates Depression-Like Behaviors in the Nucleus Accumbens

    Kim, H.-D.; Hesterman, J.; Call, T.; Magazu, S.; Keeley, E.; Armenta, K.; Kronman, H.; Nestler, E. J.; Ferguson, D.; Neve, Rachael L.
    Depression is a recurring and life-threatening illness that affects up to 120 million people worldwide. In the present study, we show that chronic social defeat stress, an ethologically validated model of depression in mice, increases SIRT1 levels in the nucleus accumbens (NAc), a key brain reward region. Increases in SIRT1, a well characterized class III histone deacetylase, after chronic social defeat suggest a role for this enzyme in mediating depression-like behaviors. When resveratrol, a pharmacological activator of SIRT1, was directly infused bilaterally into the NAc, we observed an increase in depression- and anxiety-like behaviors. Conversely, intra-NAc infusions of EX-527, a...

  14. Joint Inference in Weakly-Annotated Image Datasets via Dense Correspondence

    Rubinstein, Michael; Liu, Ce; Freeman, William T
    We present a principled framework for inferring pixel labels in weakly-annotated image datasets. Most previous, example-based approaches to computer vision rely on a large corpus of densely labeled images. However, for large, modern image datasets, such labels are expensive to obtain and are often unavailable. We establish a large-scale graphical model spanning all labeled and unlabeled images, then solve it to infer pixel labels jointly for all images in the dataset while enforcing consistent annotations over similar visual patterns. This model requires significantly less labeled data and assists in resolving ambiguities by propagating inferred annotations from images with stronger local...

  15. Non-canonical distribution and non-equilibrium transport beyond weak system-bath coupling regime: A polaron transformation approach

    Xu, Dazhi; Cao, Jianshu
    The concept of polaron, emerged from condense matter physics, describes the dynamical interaction of moving particle with its surrounding bosonic modes. This concept has been developed into a useful method to treat open quantum systems with a complete range of system-bath coupling strength. Especially, the polaron transformation approach shows its validity in the intermediate coupling regime, in which the Redfield equation or Fermi’s golden rule will fail. In the polaron frame, the equilibrium distribution carried out by perturbative expansion presents a deviation from the canonical distribution, which is beyond the usual weak coupling assumption in thermodynamics. A polaron transformed Redfield...

  16. Long-term glycemic control using polymer-encapsulated human stem cell–derived beta cells in immune-competent mice

    Gürtler, Mads; Millman, Jeffrey R; Pagliuca, Felicia W; McGarrigle, James J; Bochenek, Matthew A; Hollister-Lock, Jennifer; Oberholzer, Jose; Greiner, Dale L; Weir, Gordon C; Melton, Douglas A; Vegas, Arturo; Veiseh, Omid; Bader, Andrew; Doloff, Joshua C; Li, Jie; Chen, Michael; Olejnik, Karsten; Tam, Hok Hei; Jhunjhunwala, Siddharth; Langan, Erin; Aresta-Dasilva, Stephanie K; Gandham, Srujan Kumar; Langer, Robert S; Anderson, Daniel Griffith
    The transplantation of glucose-responsive, insulin-producing cells offers the potential for restoring glycemic control in individuals with diabetes. Pancreas transplantation and the infusion of cadaveric islets are currently implemented clinically, but these approaches are limited by the adverse effects of immunosuppressive therapy over the lifetime of the recipient and the limited supply of donor tissue. The latter concern may be addressed by recently described glucose-responsive mature beta cells that are derived from human embryonic stem cells (referred to as SC-β cells), which may represent an unlimited source of human cells for pancreas replacement therapy. Strategies to address the immunosuppression concerns include...

  17. Uniform Additivity in Classical and Quantum Information

    Cross, Andrew; Smith, Graeme; Li, Ke
    Information theory quantifies the optimal rates of resource interconversions, usually in terms of entropies. However, nonadditivity often makes evaluating entropic formulas intractable. In a few auspicious cases, additivity allows a full characterization of optimal rates. We study uniform additivity of formulas, which is easily evaluated and captures all known additive quantum formulas. Our complete characterization of uniform additivity exposes an intriguing new additive quantity and identifies a remarkable coincidence—the classical and quantum uniformly additive functions with one auxiliary variable are identical.

  18. Network-level effects of kinase inhibitors modulate TNF-α-induced apoptosis in the intestinal epithelium

    Gierut, J. J.; Lau, K. S.; Lin, Y.-J.; Genetti, C.; Samatar, A. A.; Haigis, K. M.; Wood, Levi Benjamin; Lauffenburger, Douglas A
    Individual signaling pathways operate in the context of the broader signaling network. Thus, the response of a cell to signals from the environment is affected by the state of the signaling network, such as the clinically relevant example of whether some components in the network are inhibited. The cytokine tumor necrosis factor–α (TNF-α) promotes opposing cellular behaviors under different conditions; the outcome is influenced by the state of the network. For example, in the mouse intestinal epithelium, inhibition of the mitogen-activated protein kinase (MAPK) kinase MEK alters the timing of TNF-α–induced apoptosis. We investigated whether MAPK signaling directly influences TNF-α–induced...

  19. The AXL Receptor Is a Sensor of Ligand Spatial Heterogeneity

    Meyer, Aaron Samuel; Zweemer, Jacomina M.; Lauffenburger, Douglas A
    The AXL receptor is a TAM (Tyro3, AXL, MerTK) receptor tyrosine kinase (RTK) important in physiological inflammatory processes such as blood clotting, viral infection, and innate immune-mediated cell clearance. Overexpression of the receptor in a number of solid tumors is increasingly appreciated as a key drug resistance and tumor dissemination mechanism. Although the ligand-receptor (Gas6-AXL) complex structure is known, literature reports on ligand-mediated signaling have provided conflicting conclusions regarding the influence of other factors such as phosphatidylserine binding, and a detailed, mechanistic picture of AXL activation has not emerged. Integrating quantitative experiments with mathematical modeling, we show here that AXL...

  20. High-throughput protease activity cytometry reveals dose-dependent heterogeneity in PMA-mediated ADAM17 activation

    Wu, Lidan; Claas, Allison Mary; Sarkar, Aniruddh; Lauffenburger, Douglas A; Han, Jongyoon
    As key components of autocrine signaling, pericellular proteases, a disintegrin and metalloproteinases (ADAMs) in particular, are known to impact the microenvironment of individual cells and have significant implications in various pathological situations including cancer, inflammatory and vascular diseases. There is great incentive to develop a high-throughput platform for single-cell measurement of pericellular protease activity, as it is essential for studying the heterogeneity of protease response and the corresponding cell behavioral consequences. In this work, we developed a microfluidic platform to simultaneously monitor protease activity of many single cells in a time-dependent manner. This platform isolates individual microwells rapidly on demand...

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