TY - JOUR AB - During mitotic exit, missegregated chromosomes can recruit their own nuclear envelope (NE) to form micronuclei (MN). MN have reduced functioning compared to primary nuclei in the same cell, although the two compartments appear to be structurally comparable. Here we show that over 60% of MN undergo an irreversible loss of compartmentalization during interphase due to NE collapse. This disruption of the MN, which is induced by defects in nuclear lamina assembly, drastically reduces nuclear functions and can trigger massive DNA damage. MN disruption is associated with chromatin compaction and invasion of endoplasmic reticulum (ER) tubules into the chromatin. We identified disrupted MN in both major subtypes of human non-small-cell lung cancer, suggesting that disrupted MN could be a useful objective biomarker for genomic instability in solid tumors. Our study shows that NE collapse is a key event underlying MN dysfunction and establishes a link between aberrant NE organization and aneuploidy. AU - Hatch, Emily M. AU - Fischer, Andrew H. AU - Deerinck, Thomas J. AU - HETZER, Martin W ID - 11085 IS - 1 JF - Cell KW - General Biochemistry KW - Genetics and Molecular Biology SN - 0092-8674 TI - Catastrophic nuclear envelope collapse in cancer cell micronuclei VL - 154 ER - TY - JOUR AB - The crowded intracellular environment poses a formidable challenge to experimental and theoretical analyses of intracellular transport mechanisms. Our measurements of single-particle trajectories in cytoplasm and their random-walk interpretations elucidate two of these mechanisms: molecular diffusion in crowded environments and cytoskeletal transport along microtubules. We employed acousto-optic deflector microscopy to map out the three-dimensional trajectories of microspheres migrating in the cytosolic fraction of a cellular extract. Classical Brownian motion (BM), continuous time random walk, and fractional BM were alternatively used to represent these trajectories. The comparison of the experimental and numerical data demonstrates that cytoskeletal transport along microtubules and diffusion in the cytosolic fraction exhibit anomalous (nonFickian) behavior and posses statistically distinct signatures. Among the three random-walk models used, continuous time random walk provides the best representation of diffusion, whereas microtubular transport is accurately modeled with fractional BM. AU - Regner, Benjamin M. AU - Vučinić, Dejan AU - Domnisoru, Cristina AU - Bartol, Thomas M. AU - HETZER, Martin W AU - Tartakovsky, Daniel M. AU - Sejnowski, Terrence J. ID - 11088 IS - 8 JF - Biophysical Journal KW - Biophysics SN - 0006-3495 TI - Anomalous diffusion of single particles in cytoplasm VL - 104 ER - TY - JOUR AB - Nuclear pore complex (NPC) proteins are known for their critical roles in regulating nucleocytoplasmic traffic of macromolecules across the nuclear envelope. However, recent findings suggest that some nucleoporins (Nups), including Nup98, have additional functions in developmental gene regulation. Nup98, which exhibits transcription-dependent mobility at the NPC but can also bind chromatin away from the nuclear envelope, is frequently involved in chromosomal translocations in a subset of patients suffering from acute myeloid leukemia (AML). A common paradigm suggests that Nup98 translocations cause aberrant transcription when they are recuited to aberrant genomic loci. Importantly, this model fails to account for the potential loss of wild type (WT) Nup98 function in the presence of Nup98 translocation mutants. Here we examine how the cell might regulate Nup98 nucleoplasmic protein levels to control transcription in healthy cells. In addition, we discuss the possibility that dominant negative Nup98 fusion proteins disrupt the transcriptional activity of WT Nup98 in the nucleoplasm to drive AML. AU - Franks, Tobias M. AU - HETZER, Martin W ID - 11083 IS - 3 JF - Trends in Cell Biology KW - Cell Biology SN - 0962-8924 TI - The role of Nup98 in transcription regulation in healthy and diseased cells VL - 23 ER - TY - JOUR AB - Protein turnover is an effective way of maintaining a functional proteome, as old and potentially damaged polypeptides are destroyed and replaced by newly synthesized copies. An increasing number of intracellular proteins, however, have been identified that evade this turnover process and instead are maintained over a cell's lifetime. This diverse group of long-lived proteins might be particularly prone to accumulation of damage and thus have a crucial role in the functional deterioration of key regulatory processes during ageing. AU - Toyama, Brandon H. AU - HETZER, Martin W ID - 11084 JF - Nature Reviews Molecular Cell Biology KW - Cell Biology KW - Molecular Biology SN - 1471-0072 TI - Protein homeostasis: Live long, won't prosper VL - 14 ER - TY - JOUR AB - We present the design and performance characterization of a new experimental technique for measuring individual particle charges in large ensembles of macroscopic grains. The measurement principle is qualitatively similar to that used in determining the elementary charge by Millikan in that it follows individual particle trajectories. However, by taking advantage of new technology we are able to work with macroscopic grains and achieve several orders of magnitude better resolution in charge to mass ratios. By observing freely falling grains accelerated in a horizontal electric field with a co-falling, high-speed video camera, we dramatically increase particle tracking time and measurement precision. Keeping the granular medium under vacuum, we eliminate air drag, leaving the electrostatic force as the primary source of particle accelerations in the co-moving frame. Because the technique is based on direct imaging, we can distinguish between different particle types during the experiment, opening up the possibility of studying charge transfer processes between different particle species. For the ∼300 μm diameter grains reported here, we achieve an average acceleration resolution of ∼0.008 m/s2, a force resolution of ∼500 pN, and a median charge resolution ∼6× 104 elementary charges per grain (corresponding to surface charge densities ∼1 elementary charges per μm2). The primary source of error is indeterminacy in the grain mass, but with higher resolution cameras and better optics this can be further improved. The high degree of resolution and the ability to visually identify particles of different species or sizes with direct imaging make this a powerful new tool to characterize charging processes in granular media. AU - Waitukaitis, Scott R AU - Jaeger, Heinrich ID - 115 IS - 2 JF - Review of Scientific Instruments TI - In situ granular charge measurement by free-fall videography VL - 84 ER - TY - JOUR AB - We present the spatially resolved Hα dynamics of 16 star-forming galaxies at z ∼ 0.81 using the new KMOS multi-object integral field spectrograph on the ESO Very Large Telescope. These galaxies, selected using 1.18 μm narrowband imaging from the 10 deg2 CFHT-HiZELS survey of the SA 22 hr field, are found in a ∼4 Mpc overdensity of Hα emitters and likely reside in a group/intermediate environment, but not a cluster. We confirm and identify a rich group of star-forming galaxies at z = 0.813 ± 0.003, with 13 galaxies within 1000 km s−1 of each other, and seven within a diameter of 3 Mpc. All of our galaxies are “typical” star-forming galaxies at their redshift, 0.8 ± 0.4 SFR$^*_{z = 0.8}$, spanning a range of specific star formation rates (sSFRs) of 0.2–1.1 Gyr−1 and have a median metallicity very close to solar of 12 + log(O/H) = 8.62 ± 0.06. We measure the spatially resolved Hα dynamics of the galaxies in our sample and show that 13 out of 16 galaxies can be described by rotating disks and use the data to derive inclination corrected rotation speeds of 50–275 km s−1. The fraction of disks within our sample is 75% ± 8%, consistent with previous results based on Hubble Space Telescope morphologies of Hα-selected galaxies at z ∼ 1 and confirming that disks dominate the SFR density at z ∼ 1. Our Hα galaxies are well fitted by the z ∼ 1–2 Tully–Fisher (TF) relation, confirming the evolution seen in the zero point. Apart from having, on average, higher stellar masses and lower sSFRs, our group galaxies at z = 0.81 present the same mass–metallicity and TF relation as z ∼ 1 field galaxies and are all disk galaxies. AU - Sobral, D. AU - Swinbank, A. M. AU - Stott, J. P. AU - Matthee, Jorryt J AU - Bower, R. G. AU - Smail, Ian AU - Best, P. AU - Geach, J. E. AU - Sharples, R. M. ID - 11520 IS - 2 JF - The Astrophysical Journal KW - Space and Planetary Science KW - Astronomy and Astrophysics KW - galaxies: evolution – galaxies KW - high-redshift – galaxies KW - starburst SN - 0004-637X TI - The dynamics of z=0.8 H-alpha-selected star-forming galaxies from KMOS/CF-HiZELS VL - 779 ER - TY - JOUR AB - We describe a model experiment for dynamic jamming: a two-dimensional collection of initially unjammed disks that are forced into the jammed state by uniaxial compression via a rake. This leads to a stable densification front that travels ahead of the rake, leaving regions behind it jammed. Using disk conservation in conjunction with an upper limit to the packing fraction at jamming onset, we predict the front speed as a function of packing fraction and rake speed. However, we find that the jamming front has a finite width, a feature that cannot be explained by disk conservation alone. This width appears to diverge on approach to jamming, which suggests that it may be related to growing lengthscales encountered in other jamming studies. AU - Waitukaitis, Scott R AU - Roth, Leah AU - Vitelli, Vincenzo AU - Jaeger, Heinrich ID - 116 IS - 4 JF - EPL TI - Dynamic jamming fronts VL - 102 ER - TY - JOUR AB - Given only the URL of a Web page, can we identify its language? In this article we examine this question. URL-based language classification is useful when the content of the Web page is not available or downloading the content is a waste of bandwidth and time. We built URL-based language classifiers for English, German, French, Spanish, and Italian by applying a variety of algorithms and features. As algorithms we used machine learning algorithms which are widely applied for text classification and state-of-art algorithms for language identification of text. As features we used words, various sized n-grams, and custom-made features (our novel feature set). We compared our approaches with two baseline methods, namely classification by country code top-level domains and classification by IP addresses of the hosting Web servers. We trained and tested our classifiers in a 10-fold cross-validation setup on a dataset obtained from the Open Directory Project and from querying a commercial search engine. We obtained the lowest F1-measure for English (94) and the highest F1-measure for German (98) with the best performing classifiers. We also evaluated the performance of our methods: (i) on a set of Web pages written in Adobe Flash and (ii) as part of a language-focused crawler. In the first case, the content of the Web page is hard to extract and in the second page downloading pages of the “wrong” language constitutes a waste of bandwidth. In both settings the best classifiers have a high accuracy with an F1-measure between 95 (for English) and 98 (for Italian) for the Adobe Flash pages and a precision between 90 (for Italian) and 97 (for French) for the language-focused crawler. AU - Baykan, Eda AU - Weber, Ingmar AU - Henzinger, Monika H ID - 11671 IS - 1 JF - ACM Transactions on the Web KW - Computer Networks and Communications SN - 1559-1131 TI - A comprehensive study of techniques for URL-based web page language classification VL - 7 ER - TY - CONF AB - The packing arrangement of individual particles inside a granular material and the resulting response to applied stresses depend critically on particle-particle interactions. One aspect that recently received attention are nanoscale surface features of particles, which play an important role in determining the strength of cohesive van der Waals and capillary interactions and also affect tribo-charging of grains. We describe experiments on freely falling granular streams that can detect the contributions from all three of these forces. We show that it is possible to measure the charge of individual grains and build up distributions that are detailed enough to provide stringent tests of tribo-charging models currently available. A second aspect concerns particle shape. In this case steric interactions become important and new types of aggregate behavior can be expected when non-convex particle shapes are considered that can interlock or entangle. However, a general connection between the mechanical response of a granular material and the constituents\' shape remains unknown. This has made it infeasible to tackle the "inverse packing problem", namely to start from a given, desired behavior for the aggregate as a whole and then find the particle shape the produces it. We discuss a new approach, using concepts rooted in artificial evolution that provides a way to solve this inverse problem. This approach facilitates exploring the role of arbitrary particle geometry in jammed systems and invites the discovery and design of granular matter with optimized properties. AU - Jaeger, Heinrich AU - Miskin, Marc AU - Waitukaitis, Scott R ID - 117 T2 - AIP Conference Proceedings TI - From nanoscale cohesion to macroscale entanglement: opportunities for designing granular aggregate behaviour by tailoring grain shape and interactions VL - 1542 ER - TY - JOUR AB - Matching markets play a prominent role in economic theory. A prime example of such a market is the sponsored search market. Here, as in other markets of that kind, market equilibria correspond to feasible, envy free, and bidder optimal outcomes. For settings without budgets such an outcome always exists and can be computed in polynomial-time by the so-called Hungarian Method. Moreover, every mechanism that computes such an outcome is incentive compatible. We show that the Hungarian Method can be modified so that it finds a feasible, envy free, and bidder optimal outcome for settings with budgets. We also show that in settings with budgets no mechanism that computes such an outcome can be incentive compatible for all inputs. For inputs in general position, however, the presented mechanism—as any other mechanism that computes such an outcome for settings with budgets—is incentive compatible. AU - Dütting, Paul AU - Henzinger, Monika H AU - Weber, Ingmar ID - 11759 IS - 3 JF - Information Processing Letters SN - 0020-0190 TI - Sponsored search, market equilibria, and the Hungarian Method VL - 113 ER -