@article{5749, abstract = {Parasitism creates selection for resistance mechanisms in host populations and is hypothesized to promote increased host evolvability. However, the influence of these traits on host evolution when parasites are no longer present is unclear. We used experimental evolution and whole-genome sequencing of Escherichia coli to determine the effects of past and present exposure to parasitic viruses (phages) on the spread of mutator alleles, resistance, and bacterial competitive fitness. We found that mutator alleles spread rapidly during adaptation to any of four different phage species, and this pattern was even more pronounced with multiple phages present simultaneously. However, hypermutability did not detectably accelerate adaptation in the absence of phages and recovery of fitness costs associated with resistance. Several lineages evolved phage resistance through elevated mucoidy, and during subsequent evolution in phage-free conditions they rapidly reverted to nonmucoid, phage-susceptible phenotypes. Genome sequencing revealed that this phenotypic reversion was achieved by additional genetic changes rather than by genotypic reversion of the initial resistance mutations. Insertion sequence (IS) elements played a key role in both the acquisition of resistance and adaptation in the absence of parasites; unlike single nucleotide polymorphisms, IS insertions were not more frequent in mutator lineages. Our results provide a genetic explanation for rapid reversion of mucoidy, a phenotype observed in other bacterial species including human pathogens. Moreover, this demonstrates that the types of genetic change underlying adaptation to fitness costs, and consequently the impact of evolvability mechanisms such as increased point-mutation rates, depend critically on the mechanism of resistance.}, author = {Wielgoss, Sébastien and Bergmiller, Tobias and Bischofberger, Anna M. and Hall, Alex R.}, issn = {1537-1719}, journal = {Molecular Biology and Evolution}, number = {3}, pages = {770--782}, publisher = {Oxford University Press}, title = {{Adaptation to parasites and costs of parasite resistance in mutator and nonmutator bacteria}}, doi = {10.1093/molbev/msv270}, volume = {33}, year = {2016}, } @article{5771, abstract = {Retroviruses such as HIV-1 assemble and bud from infected cells in an immature, non-infectious form. Subsequently, a series of proteolytic cleavages catalysed by the viral protease leads to a spectacular structural rearrangement of the viral particle into a mature form that is competent to fuse with and infect a new cell. Maturation involves changes in the structures of protein domains, in the interactions between protein domains, and in the architecture of the viral components that are assembled by the proteins. Tight control of proteolytic cleavages at different sites is required for successful maturation, and the process is a major target of antiretroviral drugs. Here we will describe what is known about the structures of immature and mature retrovirus particles, and about the maturation process by which one transitions into the other. Despite a wealth of available data, fundamental questions about retroviral maturation remain unanswered.}, author = {Mattei, Simone and Schur, Florian and Briggs, John AG}, issn = {1879-6257}, journal = {Current Opinion in Virology}, number = {6}, pages = {27--35}, publisher = {Elsevier}, title = {{Retrovirus maturation—an extraordinary structural transformation}}, doi = {10.1016/j.coviro.2016.02.008}, volume = {18}, year = {2016}, } @inbook{5805, abstract = {Discretization of sphere in the integer space follows a particular discretization scheme, which, in principle, conforms to some topological model. This eventually gives rise to interesting topological properties of a discrete spherical surface, which need to be investigated for its analytical characterization. This paper presents some novel results on the local topological properties of the naive model of discrete sphere. They follow from the bijection of each quadraginta octant of naive sphere with its projection map called f -map on the corresponding functional plane and from the characterization of certain jumps in the f-map. As an application, we have shown how these properties can be used in designing an efficient reconstruction algorithm for a naive spherical surface from an input voxel set when it is sparse or noisy.}, author = {Sen, Nabhasmita and Biswas, Ranita and Bhowmick, Partha}, booktitle = {Computational Topology in Image Context}, isbn = {978-3-319-39440-4}, issn = {1611-3349}, location = {Marseille, France}, pages = {253--264}, publisher = {Springer Nature}, title = {{On some local topological properties of naive discrete sphere}}, doi = {10.1007/978-3-319-39441-1_23}, volume = {9667}, year = {2016}, } @inproceedings{5806, abstract = {Although the concept of functional plane for naive plane is studied and reported in the literature in great detail, no similar study is yet found for naive sphere. This article exposes the first study in this line, opening up further prospects of analyzing the topological properties of sphere in the discrete space. We show that each quadraginta octant Q of a naive sphere forms a bijection with its projected pixel set on a unique coordinate plane, which thereby serves as the functional plane of Q, and hence gives rise to merely mono-jumps during back projection. The other two coordinate planes serve as para-functional and dia-functional planes for Q, as the former is ‘mono-jumping’ but not bijective, whereas the latter holds neither of the two. Owing to this, the quadraginta octants form symmetry groups and subgroups with equivalent jump conditions. We also show a potential application in generating a special class of discrete 3D circles based on back projection and jump bridging by Steiner voxels. A circle in this class possesses 4-symmetry, uniqueness, and bounded distance from the underlying real sphere and real plane.}, author = {Biswas, Ranita and Bhowmick, Partha}, booktitle = {Discrete Geometry for Computer Imagery}, isbn = {978-3-319-32359-6}, issn = {0302-9743}, location = {Nantes, France}, pages = {256--267}, publisher = {Springer Nature}, title = {{On functionality of quadraginta octants of naive sphere with application to circle drawing}}, doi = {10.1007/978-3-319-32360-2_20}, volume = {9647}, year = {2016}, } @inbook{5809, abstract = {A discrete spherical circle is a topologically well-connected 3D circle in the integer space, which belongs to a discrete sphere as well as a discrete plane. It is one of the most important 3D geometric primitives, but has not possibly yet been studied up to its merit. This paper is a maiden exposition of some of its elementary properties, which indicates a sense of its profound theoretical prospects in the framework of digital geometry. We have shown how different types of discretization can lead to forbidden and admissible classes, when one attempts to define the discretization of a spherical circle in terms of intersection between a discrete sphere and a discrete plane. Several fundamental theoretical results have been presented, the algorithm for construction of discrete spherical circles has been discussed, and some test results have been furnished to demonstrate its practicality and usefulness.}, author = {Biswas, Ranita and Bhowmick, Partha and Brimkov, Valentin E.}, booktitle = {Combinatorial image analysis}, isbn = {978-3-319-26144-7}, issn = {1611-3349}, location = {Kolkata, India}, pages = {86--100}, publisher = {Springer Nature}, title = {{On the connectivity and smoothness of discrete spherical circles}}, doi = {10.1007/978-3-319-26145-4_7}, volume = {9448}, year = {2016}, } @article{587, abstract = {Quantum metrology exploits entangled states of particles to improve sensing precision beyond the limit achievable with uncorrelated particles. All previous methods required detection noise levels below this standard quantum limit to realize the benefits of the intrinsic sensitivity provided by these states.We experimentally demonstrate a widely applicable method for entanglement-enhanced measurements without low-noise detection. The method involves an intermediate quantum phase magnification step that eases implementation complexity. We used it to perform squeezed-state metrology 8 decibels below the standard quantum limit with a detection system that has a noise floor 10 decibels above the standard quantum limit.}, author = {Onur Hosten and Krishnakumar, Rajiv and Engelsen, Nils J and Kasevich, Mark A}, journal = {Science}, number = {6293}, pages = {1552 -- 1555}, publisher = {American Association for the Advancement of Science}, title = {{Quantum phase magnification}}, doi = {10.1126/science.aaf3397}, volume = {352}, year = {2016}, } @article{588, abstract = {Quantum metrology uses quantum entanglement - correlations in the properties of microscopic systems - to improve the statistical precision of physical measurements. When measuring a signal, such as the phase shift of a light beam or an atomic state, a prominent limitation to achievable precision arises from the noise associated with the counting of uncorrelated probe particles. This noise, commonly referred to as shot noise or projection noise, gives rise to the standard quantum limit (SQL) to phase resolution. However, it can be mitigated down to the fundamental Heisenberg limit by entangling the probe particles. Despite considerable experimental progress in a variety of physical systems, a question that persists is whether these methods can achieve performance levels that compare favourably with optimized conventional (non-entangled) systems. Here we demonstrate an approach that achieves unprecedented levels of metrological improvement using half a million 87Rb atoms in their 'clock' states. The ensemble is 20.1 ± 0.3 decibels (100-fold) spin-squeezed via an optical-cavity-based measurement. We directly resolve small microwave-induced rotations 18.5 ± 0.3 decibels (70-fold) beyond the SQL. The single-shot phase resolution of 147 microradians achieved by the apparatus is better than that achieved by the best engineered cold atom sensors despite lower atom numbers. We infer entanglement of more than 680 ± 35 particles in the atomic ensemble. Applications include atomic clocks, inertial sensors, and fundamental physics experiments such as tests of general relativity or searches for electron electric dipole moment. To this end, we demonstrate an atomic clock measurement with a quantum enhancement of 10.5 ± 0.3 decibels (11-fold), limited by the phase noise of our microwave source.}, author = {Onur Hosten and Engelsen, Nils J and Krishnakumar, Rajiv and Kasevich, Mark A}, journal = {Nature}, number = {7587}, pages = {505 -- 508}, publisher = {Nature Publishing Group}, title = {{Measurement noise 100 times lower than the quantum-projection limit using entangled atoms}}, doi = {10.1038/nature16176}, volume = {529}, year = {2016}, } @inproceedings{592, abstract = {We create up to 20 dB spin-squeezed states of atomic ensembles using an optical cavity-based measurement. The prepared states are suitable for atomic sensors that require free space release of the atoms.}, author = {Engelsen, Nils and Hosten, Onur and Krishnakumar, Rajiv and Kasevich, Mark}, location = {San Jose, CA, United States}, publisher = {IEEE}, title = {{Engineering spin squeezed states for quantum-enhanced atom interferometry}}, year = {2016}, } @article{602, abstract = {RNA polymerase (Pol) II produces messenger RNA during transcription of protein-coding genes in all eukaryotic cells. The Pol II structure is known at high resolution from X-ray crystallography for two yeast species1-3. Structural studies of mammalian Pol II, however, remain limited to low-resolution electron microscopy analysis of human Pol II and its complexes with various proteins4-10. Here we report the 3.4 Å resolution cryo-electron microscopy structure of mammalian Pol II in the form of a transcribing complex comprising DNA template and RNA transcript. We use bovine Pol II, which is identical to the human enzyme except for seven amino-acid residues. The obtained atomic model closely resembles its yeast counterpart, but also reveals unknown features. Binding of nucleic acids to the polymerase involves 'induced fit' of the mobile Pol II clamp and active centre region. DNA downstream of the transcription bubble contacts a conserved 'TPSA motif' in the jaw domain of the Pol II subunit RPB5, an interaction that is apparently already established during transcription initiation7. Upstream DNA emanates from the active centre cleft at an angle of approximately 105° with respect to downstream DNA. This position of upstream DNA allows for binding of the general transcription elongation factor DSIF (SPT4-SPT5) that we localize over the active centre cleft in a conserved position on the clamp domain of Pol II. Our results define the structure of mammalian Pol II in its functional state, indicate that previous crystallographic analysis of yeast Pol II is relevant for understanding gene transcription in all eukaryotes, and provide a starting point for a mechanistic analysis of human transcription.}, author = {Bernecky, Carrie A and Herzog, Franz and Baumeister, Wolfgang and Plitzko, Jürgen and Cramer, Patrick}, journal = {Nature}, number = {7587}, pages = {551 -- 554}, publisher = {Nature Publishing Group}, title = {{Structure of transcribing mammalian RNA polymerase II}}, doi = {10.1038/nature16482}, volume = {529}, year = {2016}, } @article{6732, abstract = {Consider the transmission of a polar code of block length N and rate R over a binary memoryless symmetric channel W and let P e be the block error probability under successive cancellation decoding. In this paper, we develop new bounds that characterize the relationship of the parameters R, N, P e , and the quality of the channel W quantified by its capacity I(W) and its Bhattacharyya parameter Z(W). In previous work, two main regimes were studied. In the error exponent regime, the channel W and the rate R <; I(W) are fixed, and it was proved that the error probability Pe scales roughly as 2 -√N . In the scaling exponent approach, the channel W and the error probability Pe are fixed and it was proved that the gap to capacity I(W) - R scales as N -1/μ . Here, μ is called scaling exponent and this scaling exponent depends on the channel W. A heuristic computation for the binary erasure channel (BEC) gives μ = 3.627 and it was shown that, for any channel W, 3.579 ≤ μ ≤ 5.702. Our contributions are as follows. First, we provide the tighter upper bound μ <;≤ 4.714 valid for any W. With the same technique, we obtain the upper bound μ ≤ 3.639 for the case of the BEC; this upper bound approaches very closely the heuristically derived value for the scaling exponent of the erasure channel. Second, we develop a trade-off between the gap to capacity I(W)- R and the error probability Pe as the functions of the block length N. In other words, we neither fix the gap to capacity (error exponent regime) nor the error probability (scaling exponent regime), but we do consider a moderate deviations regime in which we study how fast both quantities, as the functions of the block length N, simultaneously go to 0. Third, we prove that polar codes are not affected by error floors. To do so, we fix a polar code of block length N and rate R. Then, we vary the channel W and study the impact of this variation on the error probability. We show that the error probability Pe scales as the Bhattacharyya parameter Z(W) raised to a power that scales roughly like VN. This agrees with the scaling in the error exponent regime.}, author = {Mondelli, Marco and Hassani, S. Hamed and Urbanke, Rudiger L.}, issn = {1557-9654}, journal = {IEEE Transactions on Information Theory}, number = {12}, pages = {6698--6712}, publisher = {IEEE}, title = {{Unified scaling of polar codes: Error exponent, scaling exponent, moderate deviations, and error floors}}, doi = {10.1109/tit.2016.2616117}, volume = {62}, year = {2016}, } @inproceedings{6733, abstract = {The question whether RM codes are capacity-achieving is a long-standing open problem in coding theory that was recently answered in the affirmative for transmission over erasure channels [1], [2]. Remarkably, the proof does not rely on specific properties of RM codes, apart from their symmetry. Indeed, the main technical result consists in showing that any sequence of linear codes, with doubly-transitive permutation groups, achieves capacity on the memoryless erasure channel under bit-MAP decoding. Thus, a natural question is what happens under block-MAP decoding. In [1], [2], by exploiting further symmetries of the code, the bit-MAP threshold was shown to be sharp enough so that the block erasure probability also converges to 0. However, this technique relies heavily on the fact that the transmission is over an erasure channel. We present an alternative approach to strengthen results regarding the bit-MAP threshold to block-MAP thresholds. This approach is based on a careful analysis of the weight distribution of RM codes. In particular, the flavor of the main result is the following: assume that the bit-MAP error probability decays as N -δ , for some δ > 0. Then, the block-MAP error probability also converges to 0. This technique applies to transmission over any binary memoryless symmetric channel. Thus, it can be thought of as a first step in extending the proof that RM codes are capacity-achieving to the general case.}, author = {Kudekar, Shrinivas and Kumar, Santhosh and Mondelli, Marco and Pfister, Henry D. and Urbankez, Rudiger}, booktitle = {2016 IEEE International Symposium on Information Theory }, location = {Barcelona, Spain}, pages = {1755--1759}, publisher = {IEEE}, title = {{Comparing the bit-MAP and block-MAP decoding thresholds of Reed-Muller codes on BMS channels}}, doi = {10.1109/isit.2016.7541600}, year = {2016}, } @inproceedings{6770, abstract = {We describe a new method to compare the bit-MAP and block-MAP decoding thresholds of Reed-Muller (RM) codes for transmission over a binary memoryless symmetric channel. The question whether RM codes are capacity-achieving is a long-standing open problem in coding theory and it has recently been answered in the affirmative for transmission over erasure channels. Remarkably, the proof does not rely on specific properties of RM codes, apart from their symmetry. Indeed, the main technical result consists in showing that any sequence of linear codes, with doubly-transitive permutation groups, achieves capacity on the memoryless erasure channel under bit-MAP decoding. A natural question is what happens under block-MAP decoding. If the minimum distance of the code family is close to linear (e.g., of order N/ log(N)), then one can combine an upper bound on the bit-MAP error probability with a lower bound on the minimum distance to show that the code family is also capacity-achieving under block-MAP decoding. This strategy is successful for BCH codes. Unfortunately, the minimum distance of RM codes scales only as √N, which does not suffice to obtain the desired result. Then, one can exploit further symmetries of RM codes to show that the bit-MAP threshold is sharp enough so that the block erasure probability also tends to 0. However, this technique relies heavily on the fact that the transmission is over an erasure channel. We present an alternative approach to strengthen results regarding the bit-MAP threshold to block-MAP thresholds. This approach is based on a careful analysis of the weight distribution of RM codes. In particular, the flavor of the main result is the following: assume that the bit-MAP error probability decays as N−δ, for some δ > 0. Then, the block-MAP error probability also converges to 0. This technique applies to the transmission over any binary memoryless symmetric channel. Thus, it can be thought of as a first step in extending the proof that RM codes are capacity-achieving to the general case.}, author = {Mondelli, Marco and Kudekar, Shrinivas and Kumar, Santosh and Pfister, Henry D. and Şaşoğlu, Eren and Urbanke, Rüdiger}, booktitle = {24th International Zurich Seminar on Communications}, location = {Zurich, Switzerland}, pages = {50}, publisher = {ETH Zürich}, title = {{Reed-Muller codes: Thresholds and weight distribution}}, doi = {10.3929/ETHZ-A-010646484}, year = {2016}, } @article{100, abstract = {We introduce a scheme for preparation, manipulation, and read out of Majorana zero modes in semiconducting wires with mesoscopic superconducting islands. Our approach synthesizes recent advances in materials growth with tools commonly used in quantum-dot experiments, including gate control of tunnel barriers and Coulomb effects, charge sensing, and charge pumping. We outline a sequence of milestones interpolating between zero-mode detection and quantum computing that includes (1) detection of fusion rules for non-Abelian anyons using either proximal charge sensors or pumped current, (2) validation of a prototype topological qubit, and (3) demonstration of non-Abelian statistics by braiding in a branched geometry. The first two milestones require only a single wire with two islands, and additionally enable sensitive measurements of the system\'s excitation gap, quasiparticle poisoning rates, residual Majorana zero-mode splittings, and topological-qubit coherence times. These pre-braiding experiments can be adapted to other manipulation and read out schemes as well.}, author = {Aasen, David and Hell, Michael and Mishmash, Ryan and Higginbotham, Andrew P and Danon, Jeroen and Leijnse, Martin and Jespersen, Thomas and Folk, Joshua and Marcs, Charles and Flensberg, Karsten and Alicea, Jason}, journal = {Physical Review X}, number = {3}, publisher = {American Physical Society}, title = {{Milestones toward Majorana-based quantum computing}}, doi = {10.1103/PhysRevX.6.031016}, volume = {6}, year = {2016}, } @article{1008, abstract = {Feedback loops in biological networks, among others, enable differentiation and cell cycle progression, and increase robustness in signal transduction. In natural networks, feedback loops are often complex and intertwined, making it challenging to identify which loops are mainly responsible for an observed behavior. However, minimal synthetic replicas could allow for such identification. Here, we engineered a synthetic permease-inducer-repressor system in Saccharomyces cerevisiae to analyze if a transport-mediated positive feedback loop could be a core mechanism for the switch-like behavior in the regulation of metabolic gene networks such as the S. cerevisiae GAL system or the Escherichia coli lac operon. We characterized the synthetic circuit using deterministic and stochastic mathematical models. Similar to its natural counterparts, our synthetic system shows bistable and hysteretic behavior, and the inducer concentration range for bistability as well as the switching rates between the two stable states depend on the repressor concentration. Our results indicate that a generic permease–inducer–repressor circuit with a single feedback loop is sufficient to explain the experimentally observed bistable behavior of the natural systems. We anticipate that the approach of reimplementing natural systems with orthogonal parts to identify crucial network components is applicable to other natural systems such as signaling pathways.}, author = {Gnügge, Robert and Dharmarajan, Lekshmi and Lang, Moritz and Stelling, Jörg}, journal = {ACS Synthetic Biology}, number = {10}, pages = {1098 -- 1107}, publisher = {American Chemical Society}, title = {{An orthogonal permease–inducer–repressor feedback loop shows bistability}}, doi = {10.1021/acssynbio.6b00013}, volume = {5}, year = {2016}, } @article{101, abstract = {Majorana zero modes are quasiparticle excitations in condensed matter systems that have been proposed as building blocks of fault-tolerant quantum computers. They are expected to exhibit non-Abelian particle statistics, in contrast to the usual statistics of fermions and bosons, enabling quantum operations to be performed by braiding isolated modes around one another. Quantum braiding operations are topologically protected insofar as these modes are pinned near zero energy, with the departure from zero expected to be exponentially small as the modes become spatially separated. Following theoretical proposals, several experiments have identified signatures of Majorana modes in nanowires with proximity-induced superconductivity and atomic chains, with small amounts of mode splitting potentially explained by hybridization of Majorana modes. Here, we use Coulomb-blockade spectroscopy in an InAs nanowire segment with epitaxial aluminium, which forms a proximity-induced superconducting Coulomb island (a â ∼ Majorana islandâ (tm)) that is isolated from normal-metal leads by tunnel barriers, to measure the splitting of near-zero-energy Majorana modes. We observe exponential suppression of energy splitting with increasing wire length. For short devices of a few hundred nanometres, sub-gap state energies oscillate as the magnetic field is varied, as is expected for hybridized Majorana modes. Splitting decreases by a factor of about ten for each half a micrometre of increased wire length. For devices longer than about one micrometre, transport in strong magnetic fields occurs through a zero-energy state that is energetically isolated from a continuum, yielding uniformly spaced Coulomb-blockade conductance peaks, consistent with teleportation via Majorana modes. Our results help to explain the trivial-to-topological transition in finite systems and to quantify the scaling of topological protection with end-mode separation.}, author = {Albrecht, S M and Higginbotham, Andrew P and Jespersen, Thomas and Madsen, Morten and Kuemmeth, Ferdinand and Nygård, Jesper and Krogstrup, Peter and Marcus, Charles}, journal = {Nature}, number = {7593}, pages = {206 -- 209}, publisher = {Nature Publishing Group}, title = {{Exponential protection of zero modes in Majorana islands}}, doi = {10.1038/nature17162}, volume = {531}, year = {2016}, } @article{102, abstract = {Recent experiments have produced mounting evidence of Majorana zero modes in nanowire-superconductor hybrids. Signatures of an expected topological phase transition accompanying the onset of these modes nevertheless remain elusive. We investigate a fundamental question concerning this issue: Do well-formed Majorana modes necessarily entail a sharp phase transition in these setups? Assuming reasonable parameters, we argue that finite-size effects can dramatically smooth this putative transition into a crossover, even in systems large enough to support well-localized Majorana modes. We propose overcoming such finite-size effects by examining the behavior of low-lying excited states through tunneling spectroscopy. In particular, the excited-state energies exhibit characteristic field and density dependence, and scaling with system size, that expose an approaching topological phase transition. We suggest several experiments for extracting the predicted behavior. As a useful byproduct, the protocols also allow one to measure the wire's spin-orbit coupling directly in its superconducting environment.}, author = {Mishmash, Ryan and Aasen, David and Higginbotham, Andrew P and Alicea, Jason}, journal = {Physical Review B}, number = {24}, publisher = {American Physical Society}, title = {{Approaching a topological phase transition in Majorana nanowires}}, doi = {10.1103/PhysRevB.93.245404}, volume = {93}, year = {2016}, } @article{10376, abstract = {Nucleation processes are at the heart of a large number of phenomena, from cloud formation to protein crystallization. A recently emerging area where nucleation is highly relevant is the initiation of filamentous protein self-assembly, a process that has broad implications in many research areas ranging from medicine to nanotechnology. As such, spontaneous nucleation of protein fibrils has received much attention in recent years with many theoretical and experimental studies focusing on the underlying physical principles. In this paper we make a step forward in this direction and explore the early time behaviour of filamentous protein growth in the context of nucleation theory. We first provide an overview of the thermodynamics and kinetics of spontaneous nucleation of protein filaments in the presence of one relevant degree of freedom, namely the cluster size. In this case, we review how key kinetic observables, such as the reaction order of spontaneous nucleation, are directly related to the physical size of the critical nucleus. We then focus on the increasingly prominent case of filament nucleation that includes a conformational conversion of the nucleating building-block as an additional slow step in the nucleation process. Using computer simulations, we study the concentration dependence of the nucleation rate. We find that, under these circumstances, the reaction order of spontaneous nucleation with respect to the free monomer does no longer relate to the overall physical size of the nucleating aggregate but rather to the portion of the aggregate that actively participates in the conformational conversion. Our results thus provide a novel interpretation of the common kinetic descriptors of protein filament formation, including the reaction order of the nucleation step or the scaling exponent of lag times, and put into perspective current theoretical descriptions of protein aggregation.}, author = {Šarić, Anđela and Michaels, Thomas C. T. and Zaccone, Alessio and Knowles, Tuomas P. J. and Frenkel, Daan}, issn = {1089-7690}, journal = {The Journal of Chemical Physics}, keywords = {physical and theoretical chemistry, general physics and astronomy}, number = {21}, publisher = {American Institute of Physics}, title = {{Kinetics of spontaneous filament nucleation via oligomers: Insights from theory and simulation}}, doi = {10.1063/1.4965040}, volume = {145}, year = {2016}, } @article{10377, abstract = {The interplay of membrane proteins is vital for many biological processes, such as cellular transport, cell division, and signal transduction between nerve cells. Theoretical considerations have led to the idea that the membrane itself mediates protein self-organization in these processes through minimization of membrane curvature energy. Here, we present a combined experimental and numerical study in which we quantify these interactions directly for the first time. In our experimental model system we control the deformation of a lipid membrane by adhering colloidal particles. Using confocal microscopy, we establish that these membrane deformations cause an attractive interaction force leading to reversible binding. The attraction extends over 2.5 times the particle diameter and has a strength of three times the thermal energy (−3.3 kBT). Coarse-grained Monte-Carlo simulations of the system are in excellent agreement with the experimental results and prove that the measured interaction is independent of length scale. Our combined experimental and numerical results reveal membrane curvature as a common physical origin for interactions between any membrane-deforming objects, from nanometre-sized proteins to micrometre-sized particles.}, author = {van der Wel, Casper and Vahid, Afshin and Šarić, Anđela and Idema, Timon and Heinrich, Doris and Kraft, Daniela J.}, issn = {2045-2322}, journal = {Scientific Reports}, keywords = {multidisciplinary}, number = {1}, publisher = {Springer Nature}, title = {{Lipid membrane-mediated attraction between curvature inducing objects}}, doi = {10.1038/srep32825}, volume = {6}, year = {2016}, } @article{10378, abstract = {The ability of biological molecules to replicate themselves is the foundation of life, requiring a complex cellular machinery. However, a range of aberrant processes involve the self-replication of pathological protein structures without any additional assistance. One example is the autocatalytic generation of pathological protein aggregates, including amyloid fibrils, involved in neurodegenerative disorders. Here, we use computer simulations to identify the necessary requirements for the self-replication of fibrillar assemblies of proteins. We establish that a key physical determinant for this process is the affinity of proteins for the surfaces of fibrils. We find that self-replication can take place only in a very narrow regime of inter-protein interactions, implying a high level of sensitivity to system parameters and experimental conditions. We then compare our theoretical predictions with kinetic and biosensor measurements of fibrils formed from the Aβ peptide associated with Alzheimer’s disease. Our results show a quantitative connection between the kinetics of self-replication and the surface coverage of fibrils by monomeric proteins. These findings reveal the fundamental physical requirements for the formation of supra-molecular structures able to replicate themselves, and shed light on mechanisms in play in the proliferation of protein aggregates in nature.}, author = {Šarić, Anđela and Buell, Alexander K. and Meisl, Georg and Michaels, Thomas C. T. and Dobson, Christopher M. and Linse, Sara and Knowles, Tuomas P. J. and Frenkel, Daan}, issn = {1745-2481}, journal = {Nature Physics}, keywords = {general physics and astronomy}, number = {9}, pages = {874--880}, publisher = {Springer Nature}, title = {{Physical determinants of the self-replication of protein fibrils}}, doi = {10.1038/nphys3828}, volume = {12}, year = {2016}, } @article{10380, abstract = {Using non-equilibrium molecular dynamics simulations, it has been recently demonstrated that water molecules align in response to an imposed temperature gradient, resulting in an effective electric field. Here, we investigate how thermally induced fields depend on the underlying treatment of long-ranged interactions. For the short-ranged Wolf method and Ewald summation, we find the peak strength of the field to range between 2 × 107 and 5 × 107 V/m for a temperature gradient of 5.2 K/Å. Our value for the Wolf method is therefore an order of magnitude lower than the literature value [J. A. Armstrong and F. Bresme, J. Chem. Phys. 139, 014504 (2013); J. Armstrong et al., J. Chem. Phys. 143, 036101 (2015)]. We show that this discrepancy can be traced back to the use of an incorrect kernel in the calculation of the electrostatic field. More seriously, we find that the Wolf method fails to predict correct molecular orientations, resulting in dipole densities with opposite sign to those computed using Ewald summation. By considering two different multipole expansions, we show that, for inhomogeneous polarisations, the quadrupole contribution can be significant and even outweigh the dipole contribution to the field. Finally, we propose a more accurate way of calculating the electrostatic potential and the field. In particular, we show that averaging the microscopic field analytically to obtain the macroscopic Maxwell field reduces the error bars by up to an order of magnitude. As a consequence, the simulation times required to reach a given statistical accuracy decrease by up to two orders of magnitude.}, author = {Wirnsberger, P. and Fijan, D. and Šarić, Anđela and Neumann, M. and Dellago, C. and Frenkel, D.}, issn = {1089-7690}, journal = {The Journal of Chemical Physics}, keywords = {physical and theoretical chemistry, general physics and astronomy}, number = {22}, publisher = {American Institute of Physics}, title = {{Non-equilibrium simulations of thermally induced electric fields in water}}, doi = {10.1063/1.4953036}, volume = {144}, year = {2016}, }