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MIT Open Access Articles

Mostrando recursos 1 - 20 de 28.258

  1. Paired quantitative and qualitative assessment of the replication-competent HIV-1 reservoir and comparison with integrated proviral DNA

    Lorenzi, Julio C. C.; Cohen, Yehuda Z.; Cohn, Lillian B.; Kreider, Edward F.; Learn, Gerald H.; Oliveira, Thiago; Lavine, Christy L.; Horwitz, Joshua A.; Settler, Allison; Jankovic, Mila; Seaman, Michael S.; Hahn, Beatrice H.; Caskey, Marina; Nussenzweig, Michel C.; Barton, John P; Chakraborty, Arup K
    HIV-1-infected individuals harbor a latent reservoir of infected CD4⁺ T cells that is not eradicated by antiretroviral therapy (ART). This reservoir presents the greatest barrier to an HIV-1 cure and has remained difficult to characterize, in part, because the vast majority of integrated sequences are defective and incapable of reactivation. To characterize the replication-competent reservoir, we have combined two techniques, quantitative viral outgrowth and qualitative sequence analysis of clonal outgrowth viruses. Leukapheresis samples from four fully ART-suppressed, chronically infected individuals were assayed at two time points separated by a 4- to 6-mo interval. Overall, 54% of the viruses emerging from...

  2. Strain mapping at the micro-scale in hierarchical polymer composites with aligned carbon nanotube grafted fibers

    Mehdikhani, Mahoor; Matveeva, Anna; Lomov, Stepan V.; Gorbatikh, Larissa; Aravand, Mohammadali; Wardle, Brian L
    For the first time, micro-scale digital image correlation (μDIC) is investigated for measurement of strain fields in hierarchical fiber-reinforced composites. The methodology is developed on an exemplary alumina fiber/epoxy composite laminate with aligned carbon nanotubes (A-CNTs) grown on fibers. Utilizing environmental scanning electron microscopy and nano-scale random speckle patterns, sufficient precision is achieved to detect the influence of the A-CNTs on the deformation field around the fibers. Debonded regions at the fiber/matrix interface with openings as small as 35 nm could be detected. μDIC could identify the propagation of the debonded region based on the non-linear increase of the opening. The...

  3. Simultaneous single-step one-shot optimization with unsteady PDEs

    Günther, Stefanie; Gauger, Nicolas R.; Wang, Qiqi
    The single-step one-shot method has proven to be very efficient for PDE-constrained optimization where the partial differential equation (PDE) is solved by an iterative fixed point solver. In this approach, the simulation and optimization tasks are performed simultaneously in a single iteration. If the PDE is unsteady, finding an appropriate fixed point iteration is non-trivial. In this paper, we provide a framework that makes the single-step one-shot method applicable for unsteady PDEs that are solved by classical time-marching schemes. The one-shot method is applied to an optimal control problem with unsteady incompressible Navier-Stokes equations that are solved by an industry...

  4. On packing and covering polyhedra in infinite dimensions

    Rademacher, Luis; Toriello, Alejandro; Vielma Centeno, Juan Pablo
    We consider the natural generalizations of packing and covering polyhedra in infinite dimensions, and study issues related to duality and integrality of extreme points for these sets. Using appropriate finite truncations we give conditions under which complementary slackness holds for primal/dual pairs of the infinite linear programming problems associated with infinite packing and covering polyhedra. We also give conditions under which the extreme points are integral. We illustrate an application of our results on an infinite-horizon lot-sizing problem. Keywords: Covering polyhedron; Packing polyhedron; Infinite linear program; Complementary slackness; Integral extreme point

  5. Developmental dissociation between the maturation of procedural memory and declarative memory

    Kalra, Priya B.; Sheridan, Margaret A.; Finn, Amy Sue; Goetz, Calvin; Leonard, Julia; Gabrieli, John D. E.
    Declarative memory and procedural memory are known to be two fundamentally different kinds of memory that are dissociable in their psychological characteristics and measurement (explicit vs. implicit) and in the neural systems that subserve each kind of memory. Declarative memory abilities are known to improve from childhood through young adulthood, but the developmental maturation of procedural memory is largely unknown. We compared 10-year-old children and young adults on measures of declarative memory and working memory capacity and on four measures of procedural memory that have been strongly dissociated from declarative memory (mirror tracing, rotary pursuit, probabilistic classification, and artificial grammar)....

  6. Quantile regression with censoring and endogeneity

    Fernández-Val, Iván; Kowalski, Amanda E.; Chernozhukov, Victor V
    In this paper we develop a new censored quantile instrumental variable (CQIV) estimator and describe its properties and computation. The CQIV estimator combines Powell (1986) censored quantile regression (CQR) to deal with censoring, with a control variable approach to incorporate endogenous regressors. The CQIV estimator is obtained in two stages that are nonadditive in the unobservables. The first stage estimates a nonadditive model with infinite dimensional parameters for the control variable, such as a quantile or distribution regression model. The second stage estimates a nonadditive censored quantile regression model for the response variable of interest, including the estimated control variable...

  7. A 2km-size asteroid challenging the rubble-pile spin barrier – A case for cohesion

    Polishook, D.; Moskovitz, N.; Hinkle, M.L.; Lockhart, M.; Mommert, M.; Thirouin, A.; Thomas, C.A.; Trilling, D.; Willman, M.; Aharonson, O.; Binzel, Richard P; Burt, Brian; DeMeo, Francesca E; Person, Michael J
    The rubble pile spin barrier is an upper limit on the rotation rate of asteroids larger than ~200-300. m. Among thousands of asteroids with diameters larger than ~300. m, only a handful of asteroids are known to rotate faster than 2.0. h, all are in the sub-km range (≤0.6. km). Here we present photometric measurements suggesting that (60716) 2000 GD65, an S-complex, inner-main belt asteroid with a relatively large diameter of 2.3-0.7+0.6km, completes one rotation in 1.9529. ±. 0.0002. h. Its unique diameter and rotation period allow us to examine scenarios about asteroid internal structure and evolution: a rubble pile...

  8. Control and optimization algorithms for air transportation systems

    Balakrishnan, Hamsa
    Modern air transportation systems are complex cyber-physical networks that are critical to global travel and commerce. As the demand for air transport has grown, so have congestion, flight delays, and the resultant environmental impacts. With further growth in demand expected, we need new control techniques, and perhaps even redesign of some parts of the system, in order to prevent cascading delays and excessive pollution. In this survey, we consider examples of how we can develop control and optimization algorithms for air transportation systems that are grounded in real-world data, implement them, and test them in both simulations and in field...

  9. Loss of Protein Arginine Methyltransferase 8 Alters Synapse Composition and Function, Resulting in Behavioral Defects

    Penney, Jay; Seo, Jinsoo; Kritskiy, Oleg; Elmsaouri, Sara; Gao, Fan; Pao, Ping-Chieh; Su, Susan Chih-Chieh; Tsai, Li-Huei
    Diverse molecular mechanisms regulate synaptic composition and function in the mammalian nervous system. The multifunctional protein arginine methyltransferase 8 (PRMT8) possesses both methyltransferase and phospholipase activities. Here we examine the role of this neuron-specific protein in hippocampal plasticity and cognitive function. PRMT8 protein localizes to synaptic sites, and conditional whole-brain Prmt8 deletion results in altered levels of multiple synaptic proteins in the hippocampus, using both male and female mice. Interestingly, these altered protein levels are due to post-transcriptional mechanisms as the corresponding mRNA levels are unaffected. Strikingly, electrophysiological recordings from hippocampal slices of mice lacking PRMT8 reveal multiple defects in...

  10. Facephenes and rainbows: Causal evidence for functional and anatomical specificity of face and color processing in the human brain

    Schalk, Gerwin; Kapeller, Christoph; Guger, Christoph; Ogawa, Hiroshi; Hiroshima, Satoru; Kamada, Kyousuke; Lafer-Sousa, Rosa; Saygin, Zeynep M.; Kanwisher, Nancy
    Neuroscientists have long debated whether some regions of the human brain are exclusively engaged in a single specific mental process. Consistent with this view, fMRI has revealed cortical regions that respond selectively to certain stimulus classes such as faces. However, results from multivoxel pattern analyses (MVPA) challenge this view by demonstrating that category-selective regions often contain information about “nonpreferred” stimulus dimensions. But is this nonpreferred information causally relevant to behavior? Here we report a rare opportunity to test this question in a neurosurgical patient implanted for clinical reasons with strips of electrodes along his fusiform gyri. Broadband gamma electrocorticographic responses...

  11. Perceiving social interactions in the posterior superior temporal sulcus

    Beeler, David; Isik, Leyla; Kanwisher, Nancy
    Primates are highly attuned not just to social characteristics of individual agents, but also to social interactions between multiple agents. Here we report a neural correlate of the representation of social interactions in the human brain. Specifically, we observe a strong univariate response in the posterior superior temporal sulcus (pSTS) to stimuli depicting social interactions between two agents, compared with (i) pairs of agents not interacting with each other, (ii) physical interactions between inanimate objects, and (iii) individual animate agents pursuing goals and interacting with inanimate objects. We further show that this region contains information about the nature of the...

  12. The 4D nucleome project

    Dekker, Job; Belmont, Andrew S.; Guttman, Mitchell; Leshyk, Victor O.; Lis, John T.; Lomvardas, Stavros; O’Shea, Clodagh C.; Park, Peter J.; Ren, Bing; Politz, Joan C. Ritland; Shendure, Jay; Zhong, Sheng; Mirny, Leonid A
    The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the goal of gaining deeper mechanistic insights into how the nucleus is organized and functions. The project will develop and benchmark experimental and computational approaches for measuring genome conformation and nuclear organization, and investigate how these contribute to gene regulation and other genome functions. Validated experimental technologies will be combined with biophysical approaches to generate quantitative models of spatial genome organization in different biological states, both in cell populations and in single cells.

  13. SMC complexes differentially compact mitotic chromosomes according to genomic context

    Schalbetter, Stephanie Andrea; Belton, Jon-Matthew; Miles, Catrina; Yu, Miao; Dekker, Job; Baxter, Jonathan; Goloborodko, Anton; Fudenberg, Geoffrey; Mirny, Leonid A
    Structural maintenance of chromosomes (SMC) protein complexes are key determinants of chromosome conformation. Using Hi-C and polymer modelling, we study how cohesin and condensin, two deeply conserved SMC complexes, organize chromosomes in the budding yeast Saccharomyces cerevisiae. The canonical role of cohesin is to co-align sister chromatids, while condensin generally compacts mitotic chromosomes. We find strikingly different roles for the two complexes in budding yeast mitosis. First, cohesin is responsible for compacting mitotic chromosome arms, independently of sister chromatid cohesion. Polymer simulations demonstrate that this role can be fully accounted for through cis-looping of chromatin. Second, condensin is generally dispensable...

  14. Rapid sampling of stochastic displacements in Brownian dynamics simulations

    Balboa Usabiaga, Florencio; Donev, Aleksandar; Fiore, Andrew Michael; Swan, James W
    We present a new method for sampling stochastic displacements in Brownian Dynamics (BD) simulations of colloidal scale particles. The method relies on a new formulation for Ewald summation of the Rotne-Prager-Yamakawa (RPY) tensor, which guarantees that the real-space and wave-space contributions to the tensor are independently symmetric and positive-definite for all possible particle configurations. Brownian displacements are drawn from a superposition of two independent samples: a wave-space (far-field or long-ranged) contribution, computed using techniques from fluctuating hydrodynamics and non-uniform fast Fourier transforms; and a real-space (near-field or short-ranged) correction, computed using a Krylov subspace method. The combined computational complexity of...

  15. Microfluidic Fabrication of Colloidal Nanomaterials-Encapsulated Microcapsules for Biomolecular Sensing

    Zhang, Weixia; Abbaspourrad, Alireza; Tao, Jun; Hang, Tian; Lee, Hyomin; Weitz, David A.; Xie, Xi; Ahn, Jiyoung; Bader, Andrew; Bose, Suman; Vegas, Arturo; Lin, Jiaqi; Iverson, Nicole M.; Bisker Raviv, Gili Hana; Li, Linxian; Strano, Michael S.; Anderson, Daniel Griffith
    Implantable sensors that detect biomarkers in vivo are critical for early disease diagnostics. Although many colloidal nanomaterials have been developed into optical sensors to detect biomolecules in vitro, their application in vivo as implantable sensors is hindered by potential migration or clearance from the implantation site. One potential solution is incorporating colloidal nanosensors in hydrogel scaffold prior to implantation. However, direct contact between the nanosensors and hydrogel matrix has the potential to disrupt sensor performance. Here, we develop a hollow-microcapsule-based sensing platform that protects colloidal nanosensors from direct contact with hydrogel matrix. Using microfluidics, colloidal nanosensors were encapsulated in polyethylene...

  16. Hydrogel Nanocomposites with Independently Tunable Rheology and Mechanics

    Unterman, Shimon A.; Charles, Lyndon Fitzgerald; Strecker, Sara Elaine; Kramarenko, Denis; Pivovarchik, Dmitry; Edelman, Elazer R; Artzi, Natalie
    Hydrogels are an attractive class of biomaterials for minimally invasive local drug delivery given their injectability, tunability, high water content, and biocompatibility. Broad applicability though is challenged: relatively modest mechanical properties restrict use to soft tissues, while flow properties necessary for injectability limit implantation to dried, enclosed tissues to minimize material migration during gelation. To address these dual concerns, we designed an injectable nanocomposite hydrogel based on dextran aldehyde and a poly(amido amine) dendrimer doped with phyllosilicate nanoplatelet fillers. Balance of components allows for exfoliation of nanoplatelets, significantly changing macromer solution flow, facilitating injection and manipulation in a wide variety...

  17. Atomic Structure and Dynamics of Single Platinum Atom Interactions with Monolayer MoS

    Wang, Shanshan; Sawada, Hidetake; Samuels, Thomas; Allen, Christopher S.; Kirkland, Angus I.; Warner, Jamie H.; Li, Huashan; Han, Grace; Grossman, Jeffrey C.
    We have studied atomic level interactions between single Pt atoms and the surface of monolayer MoS₂ using aberration-corrected annular dark field scanning transmission electron microscopy at an accelerating voltage of 60 kV. Strong contrast from single Pt atoms on the atomically resolved monolayer MoS₂ lattice enables their exact position to be determined with respect to the MoS₂ lattice, revealing stable binding sites. In regions of MoS₂ free from surface contamination, the Pt atoms are localized in S vacancy sites and exhibit dynamic hopping to nearby vacancy sites driven by the energy supplied by the electron beam. However, in areas of...

  18. Investigation of a Quantum Monte Carlo Protocol To Achieve High Accuracy and High-Throughput Materials Formation Energies

    Mueller, Tim; Wagner, Lucas; Saritas, Kayahan; Grossman, Jeffrey C.
    High-throughput calculations based on density functional theory (DFT) methods have been widely implemented in the scientific community. However, depending on both the properties of interest as well as particular chemical/structural phase space, accuracy even for correct trends remains a key challenge for DFT. In this work, we evaluate the use of quantum Monte Carlo (QMC) to calculate material formation energies in a high-throughput environment. We test the performance of automated QMC calculations on 21 compounds with high quality reference data from the Committee on Data for Science and Technology (CODATA) thermodynamic database. We compare our approach to different DFT methods...

  19. Molecularly Engineered Azobenzene Derivatives for High Energy Density Solid-State Solar Thermal Fuels

    Cho, Eugene Nammyoung; Zhitomirsky, David; Han, Grace; Liu, Yun; Grossman, Jeffrey C.
    Solar thermal fuels (STFs) harvest and store solar energy in a closed cycle system through conformational change of molecules and can release the energy in the form of heat on demand. With the aim of developing tunable and optimized STFs for solid-state applications, we designed three azobenzene derivatives functionalized with bulky aromatic groups (phenyl, biphenyl, and tert-butyl phenyl groups). In contrast to pristine azobenzene, which crystallizes and makes nonuniform films, the bulky azobenzene derivatives formed uniform amorphous films that can be charged and discharged with light and heat for many cycles. Thermal stability of the films, a critical metric for...

  20. Process Control of Atomic Layer Deposition Molybdenum Oxide Nucleation and Sulfidation to Large-Area MoS

    Bertuch, Adam; Provine, J.; Sundaram, Ganesh; Ferralis, Nicola; Grossman, Jeffrey C.; Keller, Brent D.
    Recent advances in the field of two-dimensional (2D) transition metal dichalcogenide (TMD) materials have indicated that atomic layer deposition (ALD) of the metal oxide and subsequent sulfidation could offer a method for the synthesis of large area two-dimensional materials such as MoS 2 with excellent layer control over the entire substrate. However, growing large area oxide films by ALD with sub 1 nm nucleation coalescence remains a significant challenge, and the necessary steps are unexplored. In this work, we demonstrate the necessary process improvements required to achieve sub 1 nm nucleation control by characterization of nucleation domains formed by oxide...

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