@article{1171, author = {Tkacik, Gasper}, journal = {Physics of Life Reviews}, pages = {166 -- 167}, publisher = {Elsevier}, title = {{Understanding regulatory networks requires more than computing a multitude of graph statistics: Comment on "Drivers of structural features in gene regulatory networks: From biophysical constraints to biological function" by O. C. Martin et al.}}, doi = {10.1016/j.plrev.2016.06.005}, volume = {17}, year = {2016}, } @article{1172, abstract = {A central issue in cell biology is the physico-chemical basis of organelle biogenesis in intracellular trafficking pathways, its most impressive manifestation being the biogenesis of Golgi cisternae. At a basic level, such morphologically and chemically distinct compartments should arise from an interplay between the molecular transport and chemical maturation. Here, we formulate analytically tractable, minimalist models, that incorporate this interplay between transport and chemical progression in physical space, and explore the conditions for de novo biogenesis of distinct cisternae. We propose new quantitative measures that can discriminate between the various models of transport in a qualitative manner-this includes measures of the dynamics in steady state and the dynamical response to perturbations of the kind amenable to live-cell imaging.}, author = {Sachdeva, Himani and Barma, Mustansir and Rao, Madan}, journal = {Scientific Reports}, publisher = {Nature Publishing Group}, title = {{Nonequilibrium description of de novo biogenesis and transport through Golgi-like cisternae}}, doi = {10.1038/srep38840}, volume = {6}, year = {2016}, } @article{1177, abstract = {Boldyreva, Palacio and Warinschi introduced a multiple forking game as an extension of general forking. The notion of (multiple) forking is a useful abstraction from the actual simulation of cryptographic scheme to the adversary in a security reduction, and is achieved through the intermediary of a so-called wrapper algorithm. Multiple forking has turned out to be a useful tool in the security argument of several cryptographic protocols. However, a reduction employing multiple forking incurs a significant degradation of (Formula presented.) , where (Formula presented.) denotes the upper bound on the underlying random oracle calls and (Formula presented.) , the number of forkings. In this work we take a closer look at the reasons for the degradation with a tighter security bound in mind. We nail down the exact set of conditions for success in the multiple forking game. A careful analysis of the cryptographic schemes and corresponding security reduction employing multiple forking leads to the formulation of ‘dependence’ and ‘independence’ conditions pertaining to the output of the wrapper in different rounds. Based on the (in)dependence conditions we propose a general framework of multiple forking and a General Multiple Forking Lemma. Leveraging (in)dependence to the full allows us to improve the degradation factor in the multiple forking game by a factor of (Formula presented.). By implication, the cost of a single forking involving two random oracles (augmented forking) matches that involving a single random oracle (elementary forking). Finally, we study the effect of these observations on the concrete security of existing schemes employing multiple forking. We conclude that by careful design of the protocol (and the wrapper in the security reduction) it is possible to harness our observations to the full extent.}, author = {Kamath Hosdurg, Chethan and Chatterjee, Sanjit}, journal = {Algorithmica}, number = {4}, pages = {1321 -- 1362}, publisher = {Springer}, title = {{A closer look at multiple-forking: Leveraging (in)dependence for a tighter bound}}, doi = {10.1007/s00453-015-9997-6}, volume = {74}, year = {2016}, } @inproceedings{1179, abstract = {Computational notions of entropy have recently found many applications, including leakage-resilient cryptography, deterministic encryption or memory delegation. The two main types of results which make computational notions so useful are (1) Chain rules, which quantify by how much the computational entropy of a variable decreases if conditioned on some other variable (2) Transformations, which quantify to which extend one type of entropy implies another. Such chain rules and transformations typically lose a significant amount in quality of the entropy, and are the reason why applying these results one gets rather weak quantitative security bounds. In this paper we for the first time prove lower bounds in this context, showing that existing results for transformations are, unfortunately, basically optimal for non-adaptive black-box reductions (and it’s hard to imagine how non black-box reductions or adaptivity could be useful here.) A variable X has k bits of HILL entropy of quality (ϵ,s) if there exists a variable Y with k bits min-entropy which cannot be distinguished from X with advantage ϵ by distinguishing circuits of size s. A weaker notion is Metric entropy, where we switch quantifiers, and only require that for every distinguisher of size s, such a Y exists. We first describe our result concerning transformations. By definition, HILL implies Metric without any loss in quality. Metric entropy often comes up in applications, but must be transformed to HILL for meaningful security guarantees. The best known result states that if a variable X has k bits of Metric entropy of quality (ϵ,s) , then it has k bits of HILL with quality (2ϵ,s⋅ϵ2). We show that this loss of a factor Ω(ϵ−2) in circuit size is necessary. In fact, we show the stronger result that this loss is already necessary when transforming so called deterministic real valued Metric entropy to randomised boolean Metric (both these variants of Metric entropy are implied by HILL without loss in quality). The chain rule for HILL entropy states that if X has k bits of HILL entropy of quality (ϵ,s) , then for any variable Z of length m, X conditioned on Z has k−m bits of HILL entropy with quality (ϵ,s⋅ϵ2/2m). We show that a loss of Ω(2m/ϵ) in circuit size necessary here. Note that this still leaves a gap of ϵ between the known bound and our lower bound.}, author = {Pietrzak, Krzysztof Z and Maciej, Skorski}, location = {Beijing, China}, pages = {183 -- 203}, publisher = {Springer}, title = {{Pseudoentropy: Lower-bounds for chain rules and transformations}}, doi = {10.1007/978-3-662-53641-4_8}, volume = {9985}, year = {2016}, } @article{7763, abstract = {An orthogonal wavelet basis is characterized by its approximation order, which relates to the ability of the basis to represent general smooth functions on a given scale. It is known, though perhaps not widely known, that there are ways of exceeding the approximation order, i.e., achieving higher-order error in the discretized wavelet transform and its inverse. The focus here is on the development of a practical formulation to accomplish this first for 1D smooth functions, then for 1D functions with discontinuities and then for multidimensional (here 2D) functions with discontinuities. It is shown how to transcend both the wavelet approximation order and the 2D Gibbs phenomenon in representing electromagnetic fields at discontinuous dielectric interfaces that do not simply follow the wavelet-basis grid.}, author = {Lombardini, Richard and Acevedo, Ramiro and Kuczala, Alexander and Keys, Kerry P. and Goodrich, Carl Peter and Johnson, Bruce R.}, issn = {0021-9991}, journal = {Journal of Computational Physics}, pages = {244--262}, publisher = {Elsevier}, title = {{Higher-order wavelet reconstruction/differentiation filters and Gibbs phenomena}}, doi = {10.1016/j.jcp.2015.10.035}, volume = {305}, year = {2016}, } @article{7764, abstract = {States of self stress, organizations of internal forces in many-body systems that are in equilibrium with an absence of external forces, can be thought of as the constitutive building blocks of the elastic response of a material. In overconstrained disordered packings they have a natural mathematical correspondence with the zero-energy vibrational modes in underconstrained systems. While substantial attention in the literature has been paid to diverging length scales associated with zero- and finite-energy vibrational modes in jammed systems, less is known about the spatial structure of the states of self stress. In this work we define a natural way in which a unique state of self stress can be associated with each bond in a disordered spring network derived from a jammed packing, and then investigate the spatial structure of these bond-localized states of self stress. This allows for an understanding of how the elastic properties of a system would change upon changing the strength or even existence of any bond in the system.}, author = {Sussman, Daniel M. and Goodrich, Carl Peter and Liu, Andrea J.}, issn = {1744-683X}, journal = {Soft Matter}, number = {17}, pages = {3982--3990}, publisher = {Royal Society of Chemistry}, title = {{Spatial structure of states of self stress in jammed systems}}, doi = {10.1039/c6sm00094k}, volume = {12}, year = {2016}, } @inproceedings{785, abstract = {High memory contention is generally agreed to be a worst-case scenario for concurrent data structures. There has been a significant amount of research effort spent investigating designs which minimize contention, and several programming techniques have been proposed to mitigate its effects. However, there are currently few architectural mechanisms to allow scaling contended data structures at high thread counts. In this paper, we investigate hardware support for scalable contended data structures. We propose Lease/Release, a simple addition to standard directory-based MSI cache coherence protocols, allowing participants to lease memory, at the granularity of cache lines, by delaying coherence messages for a short, bounded period of time. Our analysis shows that Lease/Release can significantly reduce the overheads of contention for both non-blocking (lock-free) and lock-based data structure implementations, while ensuring that no deadlocks are introduced. We validate Lease/Release empirically on the Graphite multiprocessor simulator, on a range of data structures, including queue, stack, and priority queue implementations, as well as on transactional applications. Results show that Lease/Release consistently improves both throughput and energy usage, by up to 5x, both for lock-free and lock-based data structure designs.}, author = {Haider, Syed and Hasenplaugh, William and Alistarh, Dan-Adrian}, publisher = {ACM}, title = {{Lease/Release: Architectural support for scaling contended data structures}}, doi = {10.1145/2851141.2851155}, volume = {12-16-March-2016}, year = {2016}, } @article{786, abstract = {Lock-free concurrent algorithms guarantee that some concurrent operation will always make progress in a finite number of steps. Yet programmers prefer to treat concurrent code as if it were wait-free, guaranteeing that all operations always make progress. Unfortunately, designing wait-free algorithms is generally a very complex task, and the resulting algorithms are not always efficient. Although obtaining efficient wait-free algorithms has been a long-time goal for the theory community, most nonblocking commercial code is only lock-free. This article suggests a simple solution to this problem.We show that for a large class of lock-free algorithms, under scheduling conditions that approximate those found in commercial hardware architectures, lock-free algorithms behave as if they are wait-free. In other words, programmers can continue to design simple lock-free algorithms instead of complex wait-free ones, and in practice, they will get wait-free progress. Our main contribution is a new way of analyzing a general class of lock-free algorithms under a stochastic scheduler. Our analysis relates the individual performance of processes to the global performance of the system using Markov chain lifting between a complex per-process chain and a simpler system progress chain. We show that lock-free algorithms are not only wait-free with probability 1 but that in fact a general subset of lock-free algorithms can be closely bounded in terms of the average number of steps required until an operation completes. To the best of our knowledge, this is the first attempt to analyze progress conditions, typically stated in relation to a worst-case adversary, in a stochastic model capturing their expected asymptotic behavior.}, author = {Alistarh, Dan-Adrian and Censor Hillel, Keren and Shavit, Nir}, journal = {Journal of the ACM}, number = {4}, publisher = {ACM}, title = {{Are lock free concurrent algorithms practically wait free }}, doi = {10.1145/2903136}, volume = {63}, year = {2016}, } @article{8020, abstract = {Balance of cortical excitation and inhibition (EI) is thought to be disrupted in several neuropsychiatric conditions, yet it is not clear how it is maintained in the healthy human brain. When EI balance is disturbed during learning and memory in animal models, it can be restabilized via formation of inhibitory replicas of newly formed excitatory connections. Here we assess evidence for such selective inhibitory rebalancing in humans. Using fMRI repetition suppression we measure newly formed cortical associations in the human brain. We show that expression of these associations reduces over time despite persistence in behavior, consistent with inhibitory rebalancing. To test this, we modulated excitation/inhibition balance with transcranial direct current stimulation (tDCS). Using ultra-high-field (7T) MRI and spectroscopy, we show that reducing GABA allows cortical associations to be re-expressed. This suggests that in humans associative memories are stored in balanced excitatory-inhibitory ensembles that lie dormant unless latent inhibitory connections are unmasked.}, author = {Barron, H.C. and Vogels, Tim P and Emir, U.E. and Makin, T.R. and O’Shea, J. and Clare, S. and Jbabdi, S. and Dolan, R.J. and Behrens, T.E.J.}, issn = {0896-6273}, journal = {Neuron}, number = {1}, pages = {191--203}, publisher = {Elsevier}, title = {{Unmasking latent inhibitory connections in human cortex to reveal dormant cortical memories}}, doi = {10.1016/j.neuron.2016.02.031}, volume = {90}, year = {2016}, } @inproceedings{8094, abstract = {With the accelerated development of robot technologies, optimal control becomes one of the central themes of research. In traditional approaches, the controller, by its internal functionality, finds appropriate actions on the basis of the history of sensor values, guided by the goals, intentions, objectives, learning schemes, and so forth. The idea is that the controller controls the world---the body plus its environment---as reliably as possible. This paper focuses on new lines of self-organization for developmental robotics. We apply the recently developed differential extrinsic synaptic plasticity to a muscle-tendon driven arm-shoulder system from the Myorobotics toolkit. In the experiments, we observe a vast variety of self-organized behavior patterns: when left alone, the arm realizes pseudo-random sequences of different poses. By applying physical forces, the system can be entrained into definite motion patterns like wiping a table. Most interestingly, after attaching an object, the controller gets in a functional resonance with the object's internal dynamics, starting to shake spontaneously bottles half-filled with water or sensitively driving an attached pendulum into a circular mode. When attached to the crank of a wheel the neural system independently discovers how to rotate it. In this way, the robot discovers affordances of objects its body is interacting with.}, author = {Martius, Georg S and Hostettler, Rafael and Knoll, Alois and Der, Ralf}, booktitle = {Proceedings of the Artificial Life Conference 2016}, isbn = {9780262339360}, location = {Cancun, Mexico}, pages = {142--143}, publisher = {MIT Press}, title = {{Self-organized control of an tendon driven arm by differential extrinsic plasticity}}, doi = {10.7551/978-0-262-33936-0-ch029}, volume = {28}, year = {2016}, } @unpublished{8128, abstract = {The stimulus selectivity of synaptic currents in cortical neurons often shows a co-tuning of excitation and inhibition, but the mechanisms that underlie the emergence and plasticity of this co-tuning are not fully understood. Using a computational model, we show that an interaction of excitatory and inhibitory synaptic plasticity reproduces both the developmental and – when combined with a disinhibitory gate – the adult plasticity of excitatory and inhibitory receptive fields in auditory cortex. The co-tuning arises from inhibitory plasticity that balances excitation and inhibition, while excitatory stimulus selectivity can result from two different mechanisms. Inhibitory inputs with a broad stimulus tuning introduce a sliding threshold as in Bienenstock-Cooper-Munro rules, introducing an excitatory stimulus selectivity at the cost of a broader inhibitory receptive field. Alternatively, input asymmetries can be amplified by synaptic competition. The latter leaves any receptive field plasticity transient, a prediction we verify in recordings in auditory cortex.}, author = {Clopath, Claudia and Vogels, Tim P and Froemke, Robert C. and Sprekeler, Henning}, booktitle = {bioRxiv}, pages = {43}, publisher = {Cold Spring Harbor Laboratory}, title = {{Receptive field formation by interacting excitatory and inhibitory synaptic plasticity}}, year = {2016}, } @article{813, abstract = {The Gag polyprotein of retroviruses drives immature virus assembly by forming hexameric protein lattices. The assembly is primarily mediated by protein-protein interactions between capsid (CA) domains and by interactions between nucleocapsid (NC) domains and RNA. Specific interactions between NC and the viral RNA are required for genome packaging. Previously reported cryoelectron microscopy analysis of immature Mason-Pfizer monkey virus (M-PMV) particles suggested that a basic region (residues RKK) in CA may serve as an additional binding site for nucleic acids. Here, we have introduced mutations into the RKK region in both bacterial and proviral M-PMV vectors and have assessed their impact on M-PMV assembly, structure, RNA binding, budding/release, nuclear trafficking, and infectivity using in vitro and in vivo systems. Our data indicate that the RKK region binds and structures nucleic acid that serves to promote virus particle assembly in the cytoplasm. Moreover, the RKK region appears to be important for recruitment of viral genomic RNA into Gag particles, and this function could be linked to changes in nuclear trafficking. Together these observations suggest that in M-PMV, direct interactions between CA and nucleic acid play important functions in the late stages of the viral life cycle.}, author = {Füzik, Tibor and Píchalová, Růžena and Florian Schur and Strohalmová, Karolína and Křížová, Ivana and Hadravová, Romana and Rumlová, Michaela and Briggs, John A and Ulbrich, Pavel and Ruml, Tomáš}, journal = {Journal of Virology}, number = {9}, pages = {4593 -- 4603}, publisher = {ASM}, title = {{Nucleic acid binding by Mason-Pfizer monkey virus CA promotes virus assembly and genome packaging}}, doi = {10.1128/JVI.03197-15}, volume = {90}, year = {2016}, } @article{816, abstract = {Immature HIV-1 assembles at and buds from the plasma membrane before proteolytic cleavage of the viral Gag polyprotein induces structural maturation. Maturation can be blocked by maturation inhibitors (MIs), thereby abolishing infectivity. The CA (capsid) and SP1 (spacer peptide 1) region of Gag is the key regulator of assembly and maturation and is the target of MIs.We applied optimized cryo-electron tomography and subtomogram averaging to resolve this region within assembled immature HIV-1 particles at 3.9 angstrom resolution and built an atomic model. The structure reveals a network of intra- And intermolecular interactions mediating immature HIV-1 assembly. The proteolytic cleavage site between CA and SP1 is inaccessible to protease.We suggest that MIs prevent CA-SP1 cleavage by stabilizing the structure, and MI resistance develops by destabilizing CA-SP1.}, author = {Florian Schur and Martin Obr and Hagen, Wim J and Wan, William and Jakobi, Arjen J and Kirkpatrick, Joanna M and Sachse, Carsten and Kraüsslich, Hans Georg and Briggs, John A}, journal = {Science}, number = {6298}, pages = {506 -- 508}, publisher = {American Association for the Advancement of Science}, title = {{An atomic model of HIV-1 capsid-SP1 reveals structures regulating assembly and maturation}}, doi = {10.1126/science.aaf9620}, volume = {353}, year = {2016}, } @article{8241, abstract = {Background: Anticancer vaccines could represent a valuable complementary strategy to established therapies, especially in settings of early stage and minimal residual disease. HER-2 is an important target for immunotherapy and addressed by the monoclonal antibody trastuzumab. We have previously generated HER-2 mimotope peptides from phage display libraries. The synthesized peptides were coupled to carriers and applied for epitope-specific induction of trastuzumab-like IgG. For simplification and to avoid methodological limitations of synthesis and coupling chemistry, we herewith present a novel and optimized approach by using adeno-associated viruses (AAV) as effective and high-density mimotope-display system, which can be directly used for vaccination. Methods: An AAV capsid display library was constructed by genetically incorporating random peptides in a plasmid encoding the wild-type AAV2 capsid protein. AAV clones, expressing peptides specifically reactive to trastuzumab, were employed to immunize BALB/c mice. Antibody titers against human HER-2 were determined, and the isotype composition and functional properties of these were tested. Finally, prophylactically immunized mice were challenged with human HER-2 transfected mouse D2F2/E2 cells. Results: HER-2 mimotope AAV-vaccines induced antibodies specific to human HER-2. Two clones were selected for immunization of mice, which were subsequently grafted D2F2/E2 cells. Both mimotope AAV clones delayed the growth of tumors significantly, as compared to controls. Conclusion: In this study, a novel mimotope AAV-based platform was created allowing the isolation of mimotopes, which can be directly used as anticancer vaccines. The example of trastuzumab AAV-mimotopes demonstrates that this vaccine strategy could help to establish active immunotherapy for breast-cancer patients.}, author = {Singer, Josef and Manzano-Szalai, Krisztina and Fazekas, Judit and Thell, Kathrin and Bentley-Lukschal, Anna and Stremnitzer, Caroline and Roth-Walter, Franziska and Weghofer, Margit and Ritter, Mirko and Pino Tossi, Kerstin and Hörer, Markus and Michaelis, Uwe and Jensen-Jarolim, Erika}, issn = {2162-402X}, journal = {OncoImmunology}, number = {7}, publisher = {Taylor & Francis}, title = {{Proof of concept study with an HER-2 mimotope anticancer vaccine deduced from a novel AAV-mimotope library platform}}, doi = {10.1080/2162402x.2016.1171446}, volume = {5}, year = {2016}, } @inproceedings{8300, abstract = {The integration of social networking concepts into Internet of Things systems is a burgeoning topic of research that promises to support novel and more powerful applications. In this paper we focus on the design and implementation of a highly scalable Trust and Reputation Model for the Internet of Things based on the social approach that the COSMOS project introduces, as part of its final results. We create our model by combining popular solutions proposed for Peer-to-Peer and mobile ad-hoc networks and adapting them on the Internet of Things concept. Each Thing can compute the Trust index of another Thing based on its own experiences, while it has the capability of determining its Reputation Index either by consulting its other “friends” (Followees) or referring to the Platform, a management system used in COSMOS. The model is tested through simulations of the proposed social system, demonstrating the ability of TRM-SIoT to achieve the Social Exclusion of malicious nodes and collectives from the network, with low computational overhead and high scalability. Furthermore, due to the adaptive nature of the system, Social Reintegration of these nodes is also possible.}, author = {Kokoris Kogias, Eleftherios and Voutyras, Orfefs and Varvarigou, Theodora}, booktitle = {2016 IEEE 21st International Conference on Emerging Technologies and Factory Automation}, isbn = {9781509013142}, location = {Berlin, Germany}, publisher = {IEEE}, title = {{TRM-SIoT: A scalable hybrid trust & reputation model for the social Internet of Things}}, doi = {10.1109/etfa.2016.7733612}, year = {2016}, } @inproceedings{8302, abstract = {While showing great promise, Bitcoin requires users to wait tens of minutes for transactions to commit, and even then, offering only probabilistic guarantees. This paper introduces ByzCoin, a novel Byzantine consensus protocol that leverages scalable collective signing to commit Bitcoin transactions irreversibly within seconds. ByzCoin achieves Byzantine consensus while preserving Bitcoin’s open membership by dynamically forming hash power-proportionate consensus groups that represent recently-successful block miners. ByzCoin employs communication trees to optimize transaction commitment and verification under normal operation while guaranteeing safety and liveness under Byzantine faults, up to a near-optimal tolerance of f faulty group members among 3f + 2 total. ByzCoin mitigates double spending and selfish mining attacks by producing collectively signed transaction blocks within one minute of transaction submission. Tree-structured communication further reduces this latency to less than 30 seconds. Due to these optimizations, ByzCoin achieves a throughput higher than Paypal currently handles, with a confirmation latency of 15-20 seconds.}, author = {Kokoris Kogias, Eleftherios and Jovanovic, Philipp and Gailly, Nicolas and Khoffi, Ismail and Gasser, Linus and Ford, Bryan}, booktitle = {Proceedings of the 25th USENIX Conference on Security Symposium}, isbn = {9781931971324}, location = {Austin, TX, United States}, pages = {279–296}, publisher = {USENIX Association}, title = {{Enhancing bitcoin security and performance with strong consistency via collective signing}}, year = {2016}, } @article{8452, abstract = {During spore formation in Bacillus subtilis a transenvelope complex is assembled across the double membrane that separates the mother cell and forespore. This complex (called the “A–Q complex”) is required to maintain forespore development and is composed of proteins with remote homology to components of type II, III, and IV secretion systems found in Gram-negative bacteria. Here, we show that one of these proteins, SpoIIIAG, which has remote homology to ring-forming proteins found in type III secretion systems, assembles into an oligomeric ring in the periplasmic-like space between the two membranes. Three-dimensional reconstruction of images generated by cryo-electron microscopy indicates that the SpoIIIAG ring has a cup-and-saucer architecture with a 6-nm central pore. Structural modeling of SpoIIIAG generated a 24-member ring with dimensions similar to those of the EM-derived saucer. Point mutations in the predicted oligomeric interface disrupted ring formation in vitro and impaired forespore gene expression and efficient spore formation in vivo. Taken together, our data provide strong support for the model in which the A–Q transenvelope complex contains a conduit that connects the mother cell and forespore. We propose that a set of stacked rings spans the intermembrane space, as has been found for type III secretion systems.}, author = {Rodrigues, Christopher D. A. and Henry, Xavier and Neumann, Emmanuelle and Kurauskas, Vilius and Bellard, Laure and Fichou, Yann and Schanda, Paul and Schoehn, Guy and Rudner, David Z. and Morlot, Cecile}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences}, number = {41}, pages = {11585--11590}, publisher = {National Academy of Sciences}, title = {{A ring-shaped conduit connects the mother cell and forespore during sporulation in Bacillus subtilis}}, doi = {10.1073/pnas.1609604113}, volume = {113}, year = {2016}, } @article{8453, abstract = {Transverse relaxation rate measurements in magic-angle spinning solid-state nuclear magnetic resonance provide information about molecular motions occurring on nanosecond-to-millisecond (ns–ms) time scales. The measurement of heteronuclear (13C, 15N) relaxation rate constants in the presence of a spin-lock radiofrequency field (R1ρ relaxation) provides access to such motions, and an increasing number of studies involving R1ρ relaxation in proteins have been reported. However, two factors that influence the observed relaxation rate constants have so far been neglected, namely, (1) the role of CSA/dipolar cross-correlated relaxation (CCR) and (2) the impact of fast proton spin flips (i.e., proton spin diffusion and relaxation). We show that CSA/D CCR in R1ρ experiments is measurable and that the CCR rate constant depends on ns–ms motions; it can thus provide insight into dynamics. We find that proton spin diffusion attenuates this CCR due to its decoupling effect on the doublet components. For measurements of dynamics, the use of R1ρ rate constants has practical advantages over the use of CCR rates, and this article reveals factors that have so far been disregarded and which are important for accurate measurements and interpretation.}, author = {Kurauskas, Vilius and Weber, Emmanuelle and Hessel, Audrey and Ayala, Isabel and Marion, Dominique and Schanda, Paul}, issn = {1520-6106}, journal = {The Journal of Physical Chemistry B}, keywords = {Physical and Theoretical Chemistry, Materials Chemistry, Surfaces, Coatings and Films}, number = {34}, pages = {8905--8913}, publisher = {American Chemical Society}, title = {{Cross-correlated relaxation of dipolar coupling and chemical-shift anisotropy in magic-angle spinning R1ρ NMR measurements: Application to protein backbone dynamics measurements}}, doi = {10.1021/acs.jpcb.6b06129}, volume = {120}, year = {2016}, } @article{8454, abstract = {Magic-angle spinning solid-state NMR spectroscopy is an important technique to study molecular structure, dynamics and interactions, and is rapidly gaining importance in biomolecular sciences. Here we provide an overview of experimental approaches to study molecular dynamics by MAS solid-state NMR, with an emphasis on the underlying theoretical concepts and differences of MAS solid-state NMR compared to solution-state NMR. The theoretical foundations of nuclear spin relaxation are revisited, focusing on the particularities of spin relaxation in solid samples under magic-angle spinning. We discuss the range of validity of Redfield theory, as well as the inherent multi-exponential behavior of relaxation in solids. Experimental challenges for measuring relaxation parameters in MAS solid-state NMR and a few recently proposed relaxation approaches are discussed, which provide information about time scales and amplitudes of motions ranging from picoseconds to milliseconds. We also discuss the theoretical basis and experimental measurements of anisotropic interactions (chemical-shift anisotropies, dipolar and quadrupolar couplings), which give direct information about the amplitude of motions. The potential of combining relaxation data with such measurements of dynamically-averaged anisotropic interactions is discussed. Although the focus of this review is on the theoretical foundations of dynamics studies rather than their application, we close by discussing a small number of recent dynamics studies, where the dynamic properties of proteins in crystals are compared to those in solution.}, author = {Schanda, Paul and Ernst, Matthias}, issn = {0079-6565}, journal = {Progress in Nuclear Magnetic Resonance Spectroscopy}, number = {8}, pages = {1--46}, publisher = {Elsevier}, title = {{Studying dynamics by magic-angle spinning solid-state NMR spectroscopy: Principles and applications to biomolecules}}, doi = {10.1016/j.pnmrs.2016.02.001}, volume = {96}, year = {2016}, } @article{8455, abstract = {Solid-state NMR spectroscopy allows the characterization of the structure, interactions and dynamics of insoluble and/or very large proteins. Sensitivity and resolution are often major challenges for obtaining atomic-resolution information, in particular for very large protein complexes. Here we show that the use of deuterated, specifically CH3-labelled proteins result in significant sensitivity gains compared to previously employed CHD2 labelling, while line widths increase only marginally. We apply this labelling strategy to a 468 kDa-large dodecameric aminopeptidase, TET2, and the 1.6 MDa-large 50S ribosome subunit of Thermus thermophilus.}, author = {Kurauskas, Vilius and Crublet, Elodie and Macek, Pavel and Kerfah, Rime and Gauto, Diego F. and Boisbouvier, Jérôme and Schanda, Paul}, issn = {1359-7345}, journal = {Chemical Communications}, keywords = {Materials Chemistry, Electronic, Optical and Magnetic Materials, General Chemistry, Surfaces, Coatings and Films, Metals and Alloys, Ceramics and Composites, Catalysis}, number = {61}, pages = {9558--9561}, publisher = {Royal Society of Chemistry}, title = {{Sensitive proton-detected solid-state NMR spectroscopy of large proteins with selective CH3labelling: Application to the 50S ribosome subunit}}, doi = {10.1039/c6cc04484k}, volume = {52}, year = {2016}, }