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Pinzke A.,The Oskar Klein Center | Pinzke A.,Copenhagen University | Oh S.P.,University of California at Santa Barbara | Pfrommer C.,Heidelberg Institute for Theoretical Studies HITS
Monthly Notices of the Royal Astronomical Society | Year: 2017

About one-third of X-ray-luminous clusters show smooth, Mpc-scale radio emission, known as giant radio haloes. One promising model for radio haloes is Fermi-II acceleration of seed relativistic electrons by compressible turbulence. The origin of these seed electrons has never been fully explored. Here, we integrate the Fokker-Planck equation of the cosmic ray (CR) electron and proton distributions when post-processing cosmological simulations of cluster formation and confront them with radio surface brightness and spectral data of Coma. For standard assumptions, structure formation shocks lead to a seed electron population that produces too centrally concentrated radio emission. Matching observations requires modifying properties of theCRpopulation (rapid streaming; enhancedCRelectron acceleration at shocks) or turbulence (increasing turbulent-to-thermal energy density with radius), but at the expense of fine-tuning. In a parameter study, we find that radio properties are exponentially sensitive to the amplitude of turbulence, which is inconsistent with small scatter in scaling relations. This sensitivity is removed if we relate the acceleration time to the turbulent dissipation time. In this case, turbulence above a threshold value provides a fixed amount of amplification; observations could thus potentially constrain the unknown CR seed population. To obtain sufficient acceleration, the turbulent magneto-hydrodynamics cascade has to terminate by transit time damping on CRs, i.e. thermal particles must be scattered by plasma instabilities. Understanding the small scatter in radio halo scaling relations may provide a rich source of insight on plasma processes in clusters. © 2016 The Authors.

Brancolini G.,CNR Institute of Neuroscience | Kokh D.B.,Heidelberg Institute for Theoretical Studies HITS | Calzolai L.,European Commission - Joint Research Center Ispra | Wade R.C.,Heidelberg Institute for Theoretical Studies HITS | And 2 more authors.
ACS Nano | Year: 2012

Protein-nanoparticle associations have important applications in nanoscience and nanotechnology such as targeted drug delivery and theranostics. However, the mechanisms by which proteins recognize nanoparticles and the determinants of specificity are still poorly understood at the microscopic level. Gold is a promising material in nanoparticles for nanobiotechnology applications because of the ease of its functionalization and its tunable optical properties. Ubiquitin is a small, cysteine-free protein (ubiquitous in eukaryotes) whose binding to gold nanoparticles has been characterized recently by nuclear magnetic resonance (NMR). To reveal the molecular basis of these protein-nanoparticle interactions, we performed simulations at multiple levels (ab initio quantum mechanics, classical molecular dynamics and Brownian dynamics) and compared the results with experimental data (circular dichroism and NMR). The results provide a model of the ensemble of structures constituting the ubiquitin-gold surface complex, and insights into the driving forces for the binding of ubiquitin to gold nanoparticles, the role of nanoparticle surfactants (citrate) in the association process, and the origin of the perturbations in the NMR chemical shifts. © 2012 American Chemical Society.

Nillegoda N.B.,German Cancer Research Center | Kirstein J.,Leibniz Institute for Molecular Pharmacology | Szlachcic A.,German Cancer Research Center | Berynskyy M.,Heidelberg Institute for Theoretical Studies HITS | And 15 more authors.
Nature | Year: 2015

Protein aggregates are the hallmark of stressed and ageing cells, and characterize several pathophysiological states1,2. Healthy metazoan cells effectively eliminate intracellular protein aggregates3,4, indicating that efficient disaggregation and/or degradation mechanisms exist. However, metazoans lack the key heat-shock protein disaggregase HSP100 of non-metazoan HSP70-dependent protein disaggregation systems5,6, and the human HSP70 system alone, even with the crucial HSP110 nucleotide exchange factor, has poor disaggregation activity in vitro4,7. This unresolved conundrum is central to protein quality control biology. Here we show that synergic cooperation between complexed J-protein co-chaperones of classes A and B unleashes highly efficient protein disaggregation activity in human and nematode HSP70 systems. Metazoan mixed-class J-protein complexes are transient, involve complementary charged regions conserved in the J-domains and carboxy-terminal domains of each J-protein class, and are flexible with respect to subunit composition. Complex formation allows J-proteins to initiate transient higher order chaperone structures involving HSP70 and interacting nucleotide exchange factors. A network of cooperative class A and B J-protein interactions therefore provides the metazoan HSP70 machinery with powerful, flexible, and finely regulatable disaggregase activity and a further level of regulation crucial for cellular protein quality control. © 2015 Macmillan Publishers Limited. All rights reserved.

Kashif Sadiq S.,University Pompeu Fabra | Kashif Sadiq S.,Heidelberg Institute for Theoretical Studies HITS
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences | Year: 2016

Retrovirus particle (virion) infectivity requires diffusion and clustering of multiple transmembrane envelope proteins (Env3) on the virion exterior, yet is triggered by protease-dependent degradation of a partially occluding, membrane-bound Gag polyprotein lattice on the virion interior. The physical mechanism underlying such coupling is unclear and only indirectly accessible via experiment. Modelling stands to provide insight but the required spatiotemporal range far exceeds current accessibility by all-atom or even coarse-grained molecular dynamics simulations. Nor do such approaches account for chemical reactions, while conversely, reaction kinetics approaches handle neither diffusion nor clustering. Here, a recently developed multiscale approach is considered that applies an ultra-coarsegraining scheme to treat entire proteins at near-single particle resolution, but which also couples chemical reactions with diffusion and interactions. A model is developed of Env3 molecules embedded in a truncated Gag lattice composed of membrane-bound matrix proteins linked to capsid subunits, with freely diffusing protease molecules. Simulations suggest that in the presence of Gag but in the absence of lateral lattice-forming interactions, Env3 diffuses comparably to Gag-absent Env3. Initial immobility of Env3 is conferred through lateral caging by matrix trimers vertically coupled to the underlying hexameric capsid layer. Gag cleavage by protease vertically decouples the matrix and capsid layers, induces both matrix and Env3 diffusion, and permits Env3 clustering. Spreading across the entire membrane surface reduces crowding, in turn, enhancing the effect and promoting infectivity. © 2016 The Author(s) Published by the Royal Society. All rights reserved.

Xia X.,Heidelberg Institute for Theoretical Studies HITS
Proceedings of the 2012 ASE International Conference on BioMedical Computing, BioMedCom 2012 | Year: 2013

The policy compliance problem is one of the categories of inconsistency problems existing between access control policies. One of the ways to cope with it is called policy comparison. In this paper we develop and use our approach to perform policy comparison, i.e. when newly specified access control policies for the resources are provided to be compared with certain original policy, we are able to ensure that the noncompliance problem between these newly specified policies and the original policies on the resources will be found. In this paper we propose the READ (Resolution and Abduction based) algorithm to be an approach of finding policy noncompliance. Our approach is based on the resolution and abduction work for Data log rules, and the evaluation of compliance is performed through set implication by Satisfiability Modulo Theories (SMT) Z3 prover. We will illustrate the implementation of READ algorithm with two examples from existing work and one example based on role based access control model. © 2012 IEEE.

Patil S.P.,Heidelberg Institute for Theoretical Studies HITS | Markert B.,RWTH Aachen | Grater F.,Heidelberg Institute for Theoretical Studies HITS
Biophysical Journal | Year: 2014

The time-dependent stress-strain behavior of spider dragline silk was already observed decades ago, and has been attributed to the disordered sequences in silk proteins, which compose the soft amorphous matrix. However, the actual molecular origin and magnitude of internal friction within the amorphous matrix has remained inaccessible, because experimentally decomposing the mechanical response of the amorphous matrix from the embedded crystalline units is challenging. Here, we used atomistic molecular dynamics simulations to obtain friction forces for the relative sliding of peptide chains of Araneus diadematus spider silk within bundles of these chains as a representative unit of the amorphous matrix in silk fibers. We computed the friction coefficient and coefficient of viscosity of the amorphous phase to be in the order of 10 -6 Ns/m and 104 Ns/m2, respectively, by extrapolating our simulation data to the viscous limit. Finally, we used a finite element method for the amorphous phase, solely based on parameters derived from molecular dynamics simulations including the newly determined coefficient of viscosity. With this model the time scales of stress relaxation, creep, and hysteresis were assessed, and found to be in line with the macroscopic time-dependent response of silk fibers. Our results suggest the amorphous phase to be the primary source of viscosity in silk and open up the avenue for finite element method studies of silk fiber mechanics including viscous effects. © 2014 Biophysical Society.

Pinzke A.,University of California at Santa Barbara | Pfrommer C.,Heidelberg Institute for Theoretical Studies HITS | Bergstrom L.,The Oskar Klein Center
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2011

We study the possibility for detecting gamma-ray emission from galaxy clusters. We consider (1) leptophilic models of dark matter (DM) annihilation that include a Sommerfeld enhancement (SFE), (2) different representative benchmark models of supersymmetric DM, and (3) cosmic-ray (CR) induced pion decay. Among all clusters/groups of a flux-limited x-ray sample, we predict Virgo, Fornax, and M49 to be the brightest DM sources and find a particularly low CR-induced background for Fornax. For a minimum substructure mass given by the DM free-streaming scale, cluster halos maximize the substructure boost for which we find a factor of 1000. Since regions around the virial radius dominate the annihilation flux of substructures, the resulting surface brightness profiles are almost flat. This makes it very challenging to detect this flux with imaging atmospheric Cherenkov telescopes since their sensitivity drops approximately linearly with radius and they typically have 5-10 linear resolution elements across a cluster. Assuming cold dark matter with a substructure mass distribution down to an Earth mass and using extended Fermi upper limits, we rule out the leptophilic models in their present form in 28 clusters, and limit the boost from SFE in M49 and Fornax to be 5. This corresponds to a limit on SFE in the Milky Way of 3, which is too small to account for the increasing positron fraction with energy as seen by PAMELA and challenges the DM interpretation. Alternatively, if SFE is realized in nature, this would imply a limiting substructure mass of M lim>104M-a problem for structure formation in most particle physics models. Using individual cluster observations, it will be challenging for Fermi to constrain our selection of DM benchmark models without SFE. The Fermi upper limits are, however, closing in on our predictions for the CR flux using an analytic model based on cosmological hydrodynamical cluster simulations. We limit the CR-to-thermal pressure in nearby bright galaxy clusters of the Fermi sample to 10% and in Norma and Coma to 3%. Thus, we will soon start to constrain the underlying CR physics such as shock acceleration efficiencies or CR transport properties. © 2011 American Physical Society.

Shi L.,Heidelberg Institute for Theoretical Studies HITS
Journal of integrative bioinformatics | Year: 2013

In systems biology, quantitative experimental data is the basis of building mathematical models. In most of the cases, they are stored in Excel files and hosted locally. To have a public database for collecting, retrieving and citing experimental raw data as well as experimental conditions is important for both experimentalists and modelers. However, the great effort needed in the data handling procedure and in the data submission procedure becomes the crucial limitation for experimentalists to contribute to a database, thereby impeding the database to deliver its benefit. Moreover, manual copy and paste operations which are commonly used in those procedures increase the chance of making mistakes. Excemplify, a web-based application, proposes a flexible and adaptable template-based solution to solve these problems. Comparing to the normal template based uploading approach, which is supported by some public databases, rather than predefining a format that is potentiall impractical, Excemplify allows users to create their own experiment-specific content templates in different experiment stages and to build corresponding knowledge bases for parsing. Utilizing the embedded knowledge of used templates, Excemplify is able to parse experimental data from the initial setup stage and generate following stages spreadsheets automatically. The proposed solution standardizes the flows of data traveling according to the standard procedures of applying the experiment, cuts down the amount of manual effort and reduces the chance of mistakes caused by manual data handling. In addition, it maintains the context of meta-data from the initial preparation manuscript and improves the data consistency. It interoperates and complements RightField and SEEK as well.

Pinzke A.,University of California at Santa Barbara | Oh S.P.,University of California at Santa Barbara | Pfrommer C.,Heidelberg Institute for Theoretical Studies HITS
Monthly Notices of the Royal Astronomical Society | Year: 2013

Many bright radio relics in the outskirts of galaxy clusters have low inferred Mach numbers, defying expectations from shock acceleration theory and heliospheric observations that the injection efficiency of relativistic particles plummets at low Mach numbers. With a suite of cosmological simulations, we follow the diffusive shock acceleration as well as radiative and Coulomb cooling of cosmic ray electrons during the assembly of a cluster. We find a substantial population of fossil electrons.When reaccelerated at a shock (through diffusive shock acceleration), they are competitive with direct injection at strong shocks and overwhelmingly dominate by many orders of magnitude at weak shocks,M< 3, which are the vast majority at the cluster periphery. Their relative importance depends on cooling physics and is robust to the shock acceleration model used. While the abundance of fossils can vary by a factor of ~10, the typical reaccelerated fossil population has radio brightness in excellent agreement with observations. Fossil electrons with 1 < γ < 100 (10 < γ < 104) provide the main seeds for reacceleration at strong (weak) shocks; we show that these are well resolved by our simulation.We construct a simple self-similar analytic model which assumes steady recent injection and cooling. It agrees well with our simulations, allowing rapid estimates and physical insight into the shape of the distribution function. We predict that the Low-Frequency Array (LOFAR) should find many more bright steep-spectrum radio relics, which are inconsistent with direct injection. A failure to take fossil cosmic ray electrons into account will lead to erroneous conclusions about the nature of particle acceleration at weak shocks; they arise from well-understood physical processes and cannot be ignored. © 2013 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.

Xia X.,Heidelberg Institute for Theoretical Studies HITS
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2013

Organizations collaborate with each other for resource sharing and task performing. To protect their resources from unauthorized access the organization domains adopt own access control models. The collaboration thus faces a problem that how a secure collaboration is built between the domains with distinct access control models. Currently there are approaches focusing on role based access control model (RBAC), where role mapping is considered to be the main technique. It assumes that all organizations adopt RBAC model, then builds a global access control policy on role mappings. However if the organization domains, also including collaboration domain, use distinct access control models, role mapping and global policy can not be built on these models. In this paper we propose an equivalent access based approach and introduce a mediator involved collaboration pattern, where access control model entities have corresponding mapping and linking sets on which the equivalent accesses are built. Collaboration also introduces the "Inter Domain Role Mapping" (IDRM) problem and we thus propose new algorithms for IDRM problem based on flat and hierarchical role structures, in addition we also introduce the necessary constraints transforming between organization and collaboration domains. Finally we analyzes our algorithms and present the testing and comparison results with existed approaches. © IFIP International Federation for Information Processing 2013.

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