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MIT Open Access Articles

Mostrando recursos 1 - 20 de 27.214

  1. Towards the identification of Idiopathic Parkinson’s Disease from the speech. New articulatory kinetic biomarkers

    Moro-Velázquez, L.; Gómez-García, J. A.; Godino Llorente, Juan Ignacio; Hufnagel, Stefanie S; Choi, Jeung-Yoon
    This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Although a large amount of acoustic indicators have already been proposed in the literature to evaluate the hypokinetic dysarthria of people with Parkinson’s Disease, the goal of this work is to identify and interpret new reliable and complementary articulatory biomarkers that could be applied to predict/evaluate Parkinson’s Disease from a diadochokinetic test, contributing to the possibility of a further multidimensional analysis of the speech of parkinsonian...

  2. Widespread Shortening of 3’ Untranslated Regions and Increased Exon Inclusion Are Evolutionarily Conserved Features of Innate Immune Responses to Infection

    Baharian, Golshid; Pagé Sabourin, Ariane; Brinkworth, Jessica F.; Nédélec, Yohann; Foley, Joseph W.; Grenier, Jean-Christophe; Siddle, Katherine J.; Dumaine, Anne; Yotova, Vania; Johnson, Zachary P.; Lanford, Robert E.; Barreiro, Luis B.; Pai, Athma A.; Burge, Christopher B
    The contribution of pre-mRNA processing mechanisms to the regulation of immune responses remains poorly studied despite emerging examples of their role as regulators of immune defenses. We sought to investigate the role of mRNA processing in the cellular responses of human macrophages to live bacterial infections. Here, we used mRNA sequencing to quantify gene expression and isoform abundances in primary macrophages from 60 individuals, before and after infection with Listeria monocytogenes and Salmonella typhimurium. In response to both bacteria we identified thousands of genes that significantly change isoform usage in response to infection, characterized by an overall increase in isoform...

  3. Inhibition of mutagenic translesion synthesis: A possible strategy for improving chemotherapy?

    Yamanaka, Kinrin; Chatterjee, Nimrat; Hemann, Michael; Walker, Graham C
    With the recent technological developments a vast amount of high-throughput data has been profiled to understand the mechanism of complex diseases. The current bioinformatics challenge is to interpret the data and underlying biology, where efficient algorithms for analyzing heterogeneous high-throughput data using biological networks are becoming increasingly valuable. In this paper, we propose a software package based on the Prize-collecting Steiner Forest graph optimization approach. The PCSF package performs fast and user-friendly network analysis of high-throughput data by mapping the data onto a biological networks such as protein-protein interaction, gene-gene interaction or any other correlation or coexpression based networks. Using...

  4. Global analysis of double-strand break processing reveals in vivo properties of the helicase-nuclease complex AddAB

    Badrinarayanan, Anjana; Le, Tung; Spille, Jan Hendrik; Cisse, Ibrahim I; Laub, Michael T
    In bacteria, double-strand break (DSB) repair via homologous recombination is thought to be initiated through the bi-directional degradation and resection of DNA ends by a helicase-nuclease complex such as AddAB. The activity of AddAB has been well-studied in vitro, with translocation speeds between 400–2000 bp/s on linear DNA suggesting that a large section of DNA around a break site is processed for repair. However, the translocation rate and activity of AddAB in vivo is not known, and how AddAB is regulated to prevent excessive DNA degradation around a break site is unclear. To examine the functions and mechanistic regulation of...

  5. PCSF: An R-package for network-based interpretation of high-throughput data

    Montemanni, Roberto; Bertoni, Francesco; Kwee, Ivo; Akhmedov, Murodzhon; Kedaigle, Amanda Joy; Escalante, Renan A.; Fraenkel, Ernest
    With the recent technological developments a vast amount of high-throughput data has been profiled to understand the mechanism of complex diseases. The current bioinformatics challenge is to interpret the data and underlying biology, where efficient algorithms for analyzing heterogeneous high-throughput data using biological networks are becoming increasingly valuable. In this paper, we propose a software package based on the Prize-collecting Steiner Forest graph optimization approach. The PCSF package performs fast and user-friendly network analysis of high-throughput data by mapping the data onto a biological networks such as protein-protein interaction, gene-gene interaction or any other correlation or coexpression based networks. Using...

  6. Multivariate pattern dependence

    Caramazza, Alfonso; Anzellotti, Stefano; Saxe, Rebecca R
    When we perform a cognitive task, multiple brain regions are engaged. Understanding how these regions interact is a fundamental step to uncover the neural bases of behavior. Most research on the interactions between brain regions has focused on the univariate responses in the regions. However, fine grained patterns of response encode important information, as shown by multivariate pattern analysis. In the present article, we introduce and apply multivariate pattern dependence (MVPD): a technique to study the statistical dependence between brain regions in humans in terms of the multivariate relations between their patterns of responses. MVPD characterizes the responses in each...

  7. Invariant recognition drives neural representations of action sequences

    Isik, Leyla; Tacchetti, Andrea; Poggio, Tomaso A
    Recognizing the actions of others from visual stimuli is a crucial aspect of human perception that allows individuals to respond to social cues. Humans are able to discriminate between similar actions despite transformations, like changes in viewpoint or actor, that substantially alter the visual appearance of a scene. This ability to generalize across complex transformations is a hallmark of human visual intelligence. Advances in understanding action recognition at the neural level have not always translated into precise accounts of the computational principles underlying what representations of action sequences are constructed by human visual cortex. Here we test the hypothesis that...

  8. A deep convolutional neural network for classification of red blood cells in sickle cell anemia

    Xu, Mengjia; Zhao, Hong; Karniadakis, George Em; Papageorgiou, Dimitrios P.; Abidi, Sabia; Dao, Ming
    Sickle cell disease (SCD) is a hematological disorder leading to blood vessel occlusion accompanied by painful episodes and even death. Red blood cells (RBCs) of SCD patients have diverse shapes that reveal important biomechanical and bio-rheological characteristics, e.g. their density, fragility, adhesive properties, etc. Hence, having an objective and effective way of RBC shape quantification and classification will lead to better insights and event ual better prognosis of the disease. To this end, we have developed an automated, high-throughput, ex-vivo RBC shape classification framework that consists of three stages. First, we present an automatic hierarchical RBC extraction method to detect...

  9. Two-dimensional AXUV-based radiated power density diagnostics on NSTX-U

    Delgado-Aparicio, L.; Bell, R. E.; Tritz, K.; Diallo, A.; Gerhardt, S. P.; LeBlanc, B.; Kozub, T. A.; Faust, Ian Charles; Parker, Ronald R; Stratton, B. C.
    A new set of radiated-power-density diagnostics for the National Spherical Torus Experiment Upgrade (NSTX-U) tokamak have been designed to measure the two-dimensional poloidal structure of the total photon emissivity profile in order to perform power balance, impurity transport, and magnetohydrodynamic studies. Multiple AXUV-diode based pinhole cameras will be installed in the same toroidal angle at various poloidal locations. The local emissivity will be obtained from several types of tomographic reconstructions. The layout and response expected for the new radially viewing poloidal arrays will be shown for different impurity concentrations to characterize the diagnostic sensitivity. The radiated power profile inverted from...

  10. Nonlinear transfer in heated L-modes approaching the L–H transition threshold in Alcator C-Mod

    Cziegler, I.; Tynan, G.R.; Diamond, P.H.; Hughes, J.W.; Hubbard, Amanda E; Irby, James Henderson; Terry, James L
    Nonlinear transfer processes between large-scale edge flows and the ambient broadband fluctuations have been shown to play a significant role in the dynamics of edge turbulence, including spreading power from coherent modes and suppressing turbulence at the formation of edge transport barriers. In order to predict thresholds of confinement regimes, both the transition dynamics and the parametric dependence of the nonlinear energy transfer must be studied. Since the expected flow damping terms depend on ion collision rates and local safety factors, recent experiments aimed also to explore the nonlinear drive at various values of the plasma current, density and amount...

  11. Dihydrogen Tetrametaphosphate, [P[subscript 4]O][subscript 12]H[subscript 2]][superscript 2] –: Synthesis, Solubilization in Organic Media, Preparation of its Anhydride [P[subscript 4]O[subscript 11]][superscript 2] – and Acidic Methyl Ester, and Conversion to Tetrametaphosphate Metal Complexes via Protonolysis

    Marino, Nadia; Jiang, Yanfeng; Chakarawet, Khetpakorn; Kohout, Andrea Laura; Nava, Matthew Jordan; Cummins, Christopher C
    Dihydrogen tetrametaphosphate [P[subscript 4]O[subscript 12]H[subscript 2]] [superscript 2]- (1) can now be synthesized and isolated as its PPN salt ([PPN] + = [N(PPh[subscript 3])[subscript 2]][superscript +]) via treatment of [PPN][subscript 4 ][P[subscript 4]O[subscript 12]] with trifluoroacetic anhydride in wet acetone; this simple procedure affords the oxoacid salt in 94% yield. A pK a of 15.83 ± 0.11 in acetonitrile was determined. [P[subscript 4]O[subscript 12]H[subscript 2]][subscript 2-] reacts with the dehydrating agent N,N′-dicyclohexylcarbodiimide to afford tetrametaphosphate anhydride [P[subscript 4]O[subscript 11]][subscript 2-] (2) in 82% yield, also as the PPN salt. From 2 a monohydrogen tetrametaphosphate ester [P[subscript 4]O[subscript 10] (OH)(OMe)][superscript 2-]...

  12. Multi-electron reactivity of a cofacial di-tin(I) cryptand: partial reduction of sulfur and selenium and reversible generation of S[subscript 3][superscript ˙−]

    Dai, Yizhe; Wu, Gang; Nocera, Daniel G.; Stauber, Julia M.; Mueller, Peter; Cummins, Christopher C
    Cofacial bimetallic tin(ii) ([Sn[subscript 2](mBDCA-5t)][superscript 2−], 1) and lead(ii) ([Pb[subscript 2](mBDCA-5t)][superscrip 2−], 2) complexes have been prepared by hexadeprotonation of hexacarboxamide cryptand mBDCA-5t-H[subscript 6] together with double Sn(ii) or Pb(ii) insertion. Reaction of 1 with elemental sulfur or selenium generates di-tin polychalcogenide complexes containing μ-E and bridging μ-E[subscript 5] ligands where E = S or Se, and the Sn(ii) centers have both been oxidized to Sn(iv). Solution and solid-state UV-Vis spectra of [(μ-S[subscript 5])Sn[subscript 2](μ-S)(mBDCA-5t)][superscript 2−] (4) indicate that the complex acts reversibly as a source of S[subscript 3][superscript −] in DMF solution with a K[subscript eq] = 0.012 ±...

  13. Shape transition of unstrained flattest single-walled carbon nanotubes under pressure

    Ou-Yang, Zhong-can; Mu, Weihua; Cao, Jianshu
    Single walled carbon nanotube's (SWCNT's) cross section can be flattened under hydrostatic pressure. One example is the cross section of a single walled carbon nanotube successively deforms from the original round shape to oval shape, then to peanut-like shape. At the transition point of reversible deformation between convex shape and concave shape, the side wall of nanotube is flattest. This flattest tube has many attractive properties. In the present work, an approximate approach is developed to determine the equilibrium shape of this unstrained flattest tube and the curvature distribution of this tube. Our results are in good agreement with recent...

  14. A unified stochastic formulation of dissipative quantum dynamics. I. Generalized hierarchical equations

    Hsieh, Chang Yu; Cao, Jianshu
    We extend a standard stochastic theory to study open quantum systems coupled to a generic quantum environment. We exemplify the general framework by studying a two-level quantum system coupled bilinearly to the three fundamental classes of non-interacting particles: bosons, fermions, and spins. In this unified stochastic approach, the generalized stochastic Liouville equation (SLE) formally captures the exact quantum dissipations when noise variables with appropriate statistics for different bath models are applied. Anharmonic effects of a non-Gaussian bath are precisely encoded in the bath multi-time correlation functions that noise variables have to satisfy. Starting from the SLE, we devise a family...

  15. Semibatch monomer addition as a general method to tune and enhance the mechanics of polymer networks via loop-defect control

    Hore, Michael J. A.; Jordan, Alex M.; Korley, LaShanda T. J.; Gu, Yuwei; Kawamoto, Ken; Zhong, Mingjiang; Chen, Mao; Olsen, Bradley D; Johnson, Jeremiah A.
    Controlling the molecular structure of amorphous cross-linked polymeric materials is a longstanding challenge. Herein, we disclose a general strategy for precise tuning of loop defects in covalent polymer gel networks. This "loop control" is achieved through a simple semibatch monomer addition protocol that can be applied to a broad range of network-forming reactions. By controlling loop defects, we demonstrate that with the same set of material precursors it is possible to tune and in several cases substantially improve network connectivity and mechanical properties (e.g., ∼600% increase in shear storage modulus). We believe that the concept of loop control via continuous...

  16. Bayesian posteriors for arbitrarily rare events

    He, Kevin; Imhof, Lorens A.; Fudenberg, Drew
    We study how much data a Bayesian observer needs to correctly infer the relative likelihoods of two events when both events are arbitrarily rare. Each period, either a blue die or a red die is tossed. The two dice land on side 1 with unknown probabilities p[subscript 1] and q[subscript 1], which can be arbitrarily low. Given a data-generating process where p[subscript 1] ≥cq[subscript 1], we are interested in how much data are required to guarantee that with high probability the observer's Bayesian posterior mean for p[subscript 1] exceeds (1-δ)c times that for q[subscript 1]. If the prior densities for...

  17. Optical visualization and quantification of enzyme activity using dynamic droplet lenses

    Zarzar, Lauren D.; Kalow, Julia Ann; He, Xinping; Walish, Joseph John; Swager, Timothy M
    In this paper, we describe an approach to measuring enzyme activity based on the reconfiguration of complex emulsions. Changes in the morphology of these complex emulsions, driven by enzyme-responsive surfactants, modulate the transmission of light through a sample. Through this method we demonstrate how simple photodetector measurements may be used to monitor enzyme kinetics. This approach is validated by quantitative measurements of enzyme activity for three different classes of enzymes (amylase, lipase, and sulfatase), relying on two distinct mechanisms for coupling droplet morphology to enzyme activity (host–guest interactions with uncaging and molecular cleavage).

  18. NEIL1 protects against aflatoxin-induced hepatocellular carcinoma in mice

    Vartanian, Vladimir; Minko, Irina G.; Egner, Patricia A.; Lin, Ying-Chih; Earley, Lauriel F.; Makar, Rosemary; Eng, Jennifer R.; Camp, Matthew T.; Li, Liang; Stone, Michael P.; Lasarev, Michael R.; Groopman, John D.; McCullough, Amanda K.; Lloyd, R. Stephen; Chawanthayatham, Supawadee; Croy, Robert G; Essigmann, John M
    Global distribution of hepatocellular carcinomas (HCCs) is dominated by its incidence in developing countries, accounting for 700,000 estimated deaths per year, with dietary exposures to aflatoxin (AFB[subscript 1]) and subsequent DNA adduct formation being a significant driver. Genetic variants that increase individual susceptibility to AFB[subscript 1]-induced HCCs are poorly understood. Herein, it is shown that the DNA base excision repair (BER) enzyme, DNA glycosylase NEIL1, efficiently recognizes and excises the highly mutagenic imidazole ring-opened AFB 1 -deoxyguanosine adduct (AFB[subscript 1]-Fapy-dG). Consistent with this in vitro result, newborn mice injected with AFB[subscript 1] show significant increases in the levels of AFB[subscript...

  19. Negative Ion Photoelectron Spectroscopy of P₂N₃⁻: Electron Affinity and Electronic Structures of P₂N₃˙

    Hou, Gao-Lei; Chen, Bo; Hrovat, David A.; Borden, Weston Thatcher; Wang, Xue-Bin; Transue, Wesley; Cummins, Christopher C
    We report here a negative ion photoelectron spectroscopy (NIPES) and ab initio study of the recently synthesized planar aromatic inorganic ion P₂N₃⁻, to investigate the electronic structures of P₂N₃⁻ and its neutral P₂N₃ radical. The adiabatic detachment energy of P₂N₃⁻ (electron affinity of P₂N₃) was determined to be 3.765 ± 0.010 eV, indicating high stability for the P₂N₃⁻ anion. Ab initio electronic structure calculations reveal the existence of five, low-lying, electronic states in the neutral P₂N₃ radical. Calculation of the Franck-Condon factors (FCFs) for each anion-to-neutral electronic transition and comparison of the resulting simulated NIPE spectrum with the vibrational structure...

  20. Negative Ion Photoelectron Spectroscopy of P₂N₃⁻: Electron Affinity and Electronic Structures of P₂N₃˙

    Hou, Gao-Lei; Chen, Bo; Hrovat, David A.; Borden, Weston Thatcher; Wang, Xue-Bin; Transue, Wesley; Cummins, Christopher C
    We report here a negative ion photoelectron spectroscopy (NIPES) and ab initio study of the recently synthesized planar aromatic inorganic ion P₂N₃⁻, to investigate the electronic structures of P₂N₃⁻ and its neutral P₂N₃ radical. The adiabatic detachment energy of P₂N₃⁻ (electron affinity of P₂N₃) was determined to be 3.765 ± 0.010 eV, indicating high stability for the P₂N₃⁻ anion. Ab initio electronic structure calculations reveal the existence of five, low-lying, electronic states in the neutral P₂N₃ radical. Calculation of the Franck-Condon factors (FCFs) for each anion-to-neutral electronic transition and comparison of the resulting simulated NIPE spectrum with the vibrational structure...

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