Reading List

From this date onwards, our reading lists will be published as the main blog.

21/10/2019
High information capacity DNA-based data storage with augmented encoding characters using degenerate bases
https://www.nature.com/articles/s41598-019-43105-w
Data storage in DNA with fewer synthesis cycles using composite DNA letters.
Anavy et al.
https://www.nature.com/articles/s41587-019-0240-x
The use of DNA as an information storage method has gained supporters thanks to the increasingly cheaper cost of massively parallel sequencing. Even though there are impressive advances in sequencing, the synthesis of precise strands of DNA is still demanding. One approach to bypass the synthesis difficulties is to increase the information storage density of DNA, so shorter sequences are required. The authors of the present papers adopt the same method to achieve a higher storage density, the use of degenerate bases. Instead of sequencing a single invariable sequence, the authors exploit parallel sequencing to analyse sequences that can contain different nucleotides at determined positions. Analysing the ratios at which the nucleotides appear in each position for the ensemble of sequences, the authors give that position one of the 15 possible identities. The increment from 4 to 15 encoding characters allow to increase the maximum information storage capacity from 2 bits/character to 3.9 bits/character, resulting in a theoretical duplication of the storage density of DNA sequences.

Fast and compact DNA logic circuits based on single-stranded gates using strand-displacing polymerase
https://www.nature.com/articles/s41565-019-0544-5
In this work by the Reif lab, we're a shown an implementation of the basic AND and OR boolean logic gates based on the use of single-stranded DNA as well as the Bst 2.0 DNA polymerase. Here, the gates serve as the templates for the outputs, requiring the given inputs (as well as fuels in the case of the OR gate) as the initiators for the synthesis of the single-stranded output. This framework enables the construction of multilayered circuits in which the dual rail logic formalism can be implemented. As a proof of concept the authors implement an algorithm capable of calculating the square root of a four-bit number, showing that the polymerase implementation of the algorithm is less prone to leak reactions, requires less DNA species to be coded as well as execution time one order of magnitude lower than the analogous strand displacement circuit.

Programming molecular topologies from single-stranded nucleic acids
https://www.nature.com/articles/s41467-018-07039-7

The objective of this work is to demonstrate a general strategy to create programmable ssDNA or ssRNA knots by hierarchical folding. These topological structures can be found naturally in biopolymers such as DNA and proteins. To create ssDNA knots, the authors use DNA paranemic crossover motifs as building blocks for the knotted nucleic acid nanostructures. The authors characterized and demonstrated two-dimensional single-stranded DNA and RNA knots using AFM. The paranemic interaction regions can be designed with different lengths and it is possible to control and guide the folding order of the knot structure by controlling the sequences and lengths of these interactions in each individual edge. These structures have the potential to be used for programming nucleic acid synthesis in target cells to produce nanostructures. Programmable ssDNA and ssRNA knots also open opportunities to engineer molecular devices for further applications.

Absolutely robust controllers for stochastic chemical reaction networks 
A biochemical controller is put forward which, when embedded into an input network, under suitable
conditions ensures that a target species displays so-called absolute concentration robustness: its equilibrium depends only on the parameters from the controller. The success of the control relies on the assumption that the controlling species does not reach an extinction (zero concentration/copy-numbers). At the stochastic level, such an assumption is ensured over suitable time intervals
by initially starting with a sufficiently high copy-number of the controlling species, and by having sufficiently slow reactions which change the controlling species copy-numbers. Under an additional assumption of zero-deficiency in a suitable reduced output network, the probability distribution
of the target species takes an approximate Poisson form. The controller is applied to a variety of examples from biochemistry, and is rigorously investigated.

Oscillations in feedback driven systems: thermodynamics and noise 
The authors look at some simple systems that can be made to oscillate if the Hamiltonian is varied over time in a way that depends on a measurement of the state (extrinsic feedback). They consider a 2-state system and a large Ising model. The authors observe that a 2-state system can oscillate with feedback, and perfect coherent oscillation (at diverging dissipation) can be obtained for only a finite number of states. This isn't possible in a conventional system without feedback. The authors also note that one must keep track of the information terms to observe that the 2nd law survives.    


12/8/2019
DNA Punch Cards: Encoding Data on Native DNA sequences via Nicking
https://www.biorxiv.org/content/10.1101/672394v3
DNA, the molecule of life, has been conceived as a form to encode, not only biological information, but also any arbitrary information in its sequence. However, even when sequencing has advanced enough to become a routine technique, the generation of arbitrary sequences not. As an alternative, the authors propose the codification of said information in nicks (cuts in only one strand of DNA), encoding one bit per cut instead of two as nucleotides.

To produce the cleaving and encode the information, a nickase that works with guide-RNAs (gRNAs) is used. Files, up to 14 kB, were encoded and retrieved using nanopore sequencing. The nicking of two adjacent position in the encoding duplex increased the cost and efficiency of the reading process. Two adjacent nicks produce the detachment of the produced single strand, and a toehold in the encoding strand that can be sequenced by a nanopore. The authors also demonstrate that toeholds allow bitwise random access with fluorescence reporters that can be retrieved with a complementary strand to make the reading process non-destructive.

Differential binding cell-SELEX method to identify cell-specific aptamers using high-throughput sequencing
https://www.nature.com/articles/s41598-019-44654-w
Aptamers are short oligonucleotides with high-affinity to a specific target molecule and they are viable alternatives to antibodies. SELEX technology has generated thousands of aptamers to specifically bind small proteins, protein, peptides… Recently, cell-SELEX was developed to generate aptamers against the surface molecules and membrane proteins of live cells as an efficient alternative for diagnosis and therapy against cancer.

Thus, the main goal of this work is the development of a differential binding cell-SELEX method using high-throughput sequencing. Cell-SELEX uses living cells to select aptamers that bind to the target cells in larger numbers compared to the control cells (the computational analysis is a similar approach as RNA-seq). In order to make this system more accurate and identify cell type-specific aptamer sequences, they reported a differential binding cell-SELEX method to identify differentially abundant aptamers on the surface of target cells and negative control cells and to calculate the statistical significance of these differences. They combine software tools for identifying differentially expressed genes, to estimate the read count of sequencing and to accurate the results. This new workflow allows not only increasing the aptamer selection rate against live cells but also to design aptamers against complex or unknown targets.

Construction of integrated gene logic-chip 
https://www.nature.com/articles/s41565-018-0202-3
In the present work, Masabuchi and collaborators present an approach for reducing susceptibility of noise of genetic circuits through spatial localization on a DNA origami structure. These localized genetic devices (or gene chips, following the nomenclature used on the paper) show decreased susceptibility to leaks caused by reaction diffusion of free-flowing components and present defined spatial constrains in which yield of the system is maximum -albeit it is a variable with which the relative expression of two genes can be tuned along copy number or promotor strength. The chips also were proved to function as modules and could implement UV or mRNA detection. The output of a module was reconfigurable by varying only the spatial disposition of the components rather than components themselves. Thus, despite the troubles that localized systems based on DNA origami might have for their in vivo implementation, their versatility might become relevant in cell-free systems

Brownian Ratchets of Life: Stochasticity Combined with Disequilibrium Produces Order
https://onlinelibrary.wiley.com/doi/10.1002/bies.201900076
In this editorial essay, Andrew Moore proposes that:
(a) Living systems exploit thermodynamic driving to rectify fluctuations.
(b) This rectification of fluctuations achieves "useful" functionality, and increased order within biological systems at the expense of the resource providing the thermodynamic driving.
(c) Biological systems use ratchet-like mechanisms to achieve this rectification and functionality, and that this is a unique feature of living matter.
(d) It is fundamentally necessary to have both the random fluctuations, and the thermodynamic drive, for this strategy to work. Either in isolation cannot achieve useful output.
(e) Temperature gradients are a potential source of the thermodynamic drive.

I personally do not agree with all of this editorial. I believe that (a) and (b) are true, but in a rather simple way. (c) is an interesting hypothesis that ratchets are peculiar to biological systems (or perhaps to biological systems and human-made engines); I'm not convinced, however, that ratchet mechanisms are fundamental to the difference between living and non-living systems. I am also not sure about (d); random (or effectively random) fluctuations seem more to be a feature of all processes with many degrees of freedom, rather than a necessary ingredient of functional living ratchets. With regard to (e), I strongly doubt that internally-generated temperature gradients are an effective source of thermodynamic driving at the cellular level; certainly, there are other more obvious sources of driving that we know are employed (high free-energy fuel molecules and electrochemical potential differences across membranes). These alternatives allow throttling of the relaxation to equilibrium, so that the free energy supply is not wasted carelessly but diverted through the devices of interest.


29/7/2019
Strand displacement: a fundamental mechanism in RNA biology?
https://arxiv.org/abs/1811.02766
Nucleic acids (DNA and RNA) are some of the central molecules in molecular biology. This review introduces general mechanism of strand displacement reaction, in which one nucleic acid strand in a formed duplex is replaced by a third invading strand. The review proceeds to outline some of the advancements in the field of strand-displacement nucleic-acid-based nanotechnology, involving successful usage of DNA and RNA as programmable molecules to construct de-novo nanostructures with predefined shapes, and molecular machines with desired dynamics. While DNA/RNA strand displacement has mainly been used to design de-novo molecular devices, it is argued in the review that this reaction also likely plays a key role in multiple cellular events such asgene recombination, CRISPR-based genome editing, and RNA cotranscriptional folding.

A programmable DNA-origami platform for studying lipid transfer between bilayers
https://www.nature.com/articles/s41589-019-0325-3
This paper placed two synaptotagmin-modified lipid vesicles with defined distance using DNA origami dimers. The synaptotagmin was able to transfer lipid between the bilayers at a distance larger than the prediction for the direct protein tunnel formation model. Therefore, this result supports shuttle model where the synaptotagmin hopping between the membranes with lipid cargoes.

A cytosine deaminase for programmable single-base RNA editing
https://science.sciencemag.org/content/365/6451/382
Inside cells, RNA can be heavily modified after it is translated from DNA. This RNA editing can add radicals, as methyl, or remove them, like deamination. Since amine groups is what determines the identity of the nitrogenous bases, its removal can modify the effective sequence of nucleic acids.

In this paper, the authors present a new tool for RNA editing called RESCUE (RNA Editing for Specific C->U Exchange). This tool is able to deaminate a specific Cytosine (C) in a sequence to transform it into Uracil (U). The system is composed of a deactivated Cas13 protein fused with a deaminase, rationally mutated to work on ds RNA and to accept C. The combination of the two proteins make the system able to bind to a specific region of the RNA where a single C will be transformed into U by the deaminase.

This system constitutes a new RNA editing tool, like REPAIR (RNA Editing for Programmable A->I Replacement), that will help to produce complex systems capable of  mutate its sequence in a directed way . Future uses of this tool ranges from the production of “Dynamic sequence” RNA systems, to therapeutic corrections of mutations in RNA.

Pattern Generation with Nucleic Acid Chemical Reaction Networks
https://pubs.acs.org/doi/abs/10.1021/acs.chemrev.8b00625
In this review, Wang and Ellington give a detailed account on the main factors that allow for the emergence of spatial patterning in chemical reaction networks (mainly differences in the diffusion rates of the different chemical species as well as the rate law and reaction rates), which are directly implementable in DNA  chemical reaction networks. The review remarks that, from the two different types of pattern formations that CRNs predict (preexisting pattern transformations through reaction diffusion and pattern generation from an homogenized reaction mixture in which stochastic noise -known in this context as Turing instability- gets amplified) only the first has been achieved so far. In principle, generation of the second type of patterns (Turing patterns) could also be achieved; the authors cite a potential prominent role of DNA walkers as an enabling technology for this feat.


15/7/2019
The effects of cascade length, kinetics and feedback loops on biological transduction dynamics in a simplified cascade model 
https://iopscience.iop.org/article/10.1088/1478-3975/6/1/016007 

In this 2009 paper, Qu and Vondriska propose an ODE model for signal transduction based on data from MAPK cascades of arbitrary length with dynamics that obey both Michaelis-Menten and Hill dynamics for the phosphorylation-dephosphorylation processes. With this model they account for how these cascades both amply signal as well as attenuate noise, observing that these systems tend to have only two stable regimes: one corresponding to no propagation and one corresponding to the positive steady state - which results in the existence of a signal threshold that allows them to filter out noise or pulsating signals below this threshold.  The model also describes how the dynamics of the system become more steep as more steps are added to the cascade or if the dynamics of the steps requires multiple phosphorylation steps. But on the other side, some of the predictions made by the model (like the presence of time-dependent oscillations if the cascade implements a feedback loop) are much more open the discussion since they have not been observed experimentally in these cascade systems and may not be arise s frequently in more complex models (i.e., those accounting for catalyst-substrate complexes and loading effects in the system dynamics).

Magic: The Gathering is Turing-Complete.
https://arxiv.org/pdf/1904.09828.pdf
In this recent submission to ArXiv the authors show that it is possible to recreate a set of rules and operations equivalent to that of a universal Turing machine in a tournament-legal deck of the popular trading card game Magic: The Gathering. From this starting point, they prove mathematically that even ignoring the  stochasticity of shuffling the deck as well as the presence of hidden information (which are inbuilt features of the game), the final result of the game is undecidable and trapped in a loop (meaning that a stop operation of  this Turing machine could never be executed based solely on the inbuilt set of rules and that in principle, any algorithm can be executed in that Turing machine). The authors use this example as a first step to create a general framework with which to evaluate the computational complexity of games and their outcomes (Magic: The Gathering being a very interesting example given that, according to the authors themselves, it has the greater number of variables that the player can account for).


 On the other side, it must be remarked that competitive Magic gaming relies on the fact that a sizable number of all the possible decks are listed in tiers, known by the players in order to counter hidden information and every movement is planned as much in advance as possible to counter stochasticity, treating the outcomes of the game as decidable -not unlike chess-. This means that this Turing-completeness reveals a fundamental flaw to this strategy (although how exploitable this fault is remains unknown).

A Universal Assay for Making DNA, RNA, and RNA–DNA Hybrid Configurations for Single-Molecule Manipulation in Two or Three Steps without Ligation.
https://www.ncbi.nlm.nih.gov/pubmed/31264849
In order to understand the properties and functions at the single-molecule level, many nucleic acid configurations have been constructed. However, in all these works, repetitive digestion and ligation reactions are necessary to make single-stranded DNA and RNA. In this project, the authors have developed an amplification-annealing assay for making all these possible configurations in fewer steps by amplifying long ssDNA and ssRNA though one-side PCR, then using in vitro transcription and finally, directly annealing them together. The unique primer is functionalized at the 5’end with a digoxigenin group and the 3’end can be also labelled with a biotin group.  Some examples that they have created are: ssDNA configurations, short ssDNA with dsDNA handles, dsDNA with ssDNA handles, DNA Holiday Junctions and torsion-constrained RNA. The main advantages of this method are the universality, time-saving, ease of design and high fidelity of the process.

Enzyme-Driven Assembly and Disassembly of Hybrid DNA-RNA Nanotubes. 
https://pubs.acs.org/doi/10.1021/jacs.9b01550
The authors present a DNA/RNA hybrid tile structure whose assembly and disassembly is controlled by enzymes that synthesize and degrade RNA strands.


In silico construction of a flexibility-based DNA Brownian ratchet for directional nanoparticle delivery. 
https://advances.sciencemag.org/content/5/4/eaav4943?rss=1
This theoretical synthetic ratchet works by cycling a nanoparticle between asymmetric and flat potentials to induce directed diffusion. The particle moves to the edge of one region on a DNA template during asymmetric potential phase and moves to the next region with some probability during plat potential phase. The potential is implemented through binding of a positively charged nanoparticle to a DNA duplex with sections of different flexibility, and changing salt conditions are used to switch between different potentials.

Frontier diagrams: Partition of phase space according to the signs of eigenvalues or sign patterns of the circuits.
https://www.worldscientific.com/doi/abs/10.1142/S0218127405014039
This paper puts forward methods for analyzing the phase spaces of systems of (non-linear) ordinary differential equations (ODEs), based on the analysis of the underlying Jacobian (linearization) matrix at each points of the phase space (and not only in neighbourhoods of the underlying fixed points). More precisely, two approaches are considered. Firstly, the phase space is partitioned according to the signs of the eigenvalues and slopes of the eigenvectors of the Jacobian matrix. Secondly, the phase space is partitioned according to signs of the so-called nuclei - feedback circuits present in the Jacobian matrix, which involve all of the dependent variables from the underlying ODEs. The partitioning frontiers are obtained for a number of example ODEs. The methods are put forward for analyzing the dynamics of ODEs, as well as for designing ODEs with desired phase space features.

Ice as a protocellular medium for RNA replication
https://www.nature.com/articles/ncomms1076
The authors propose that RNA polymerase ribozymes may have benefited from freezing conditions in the early days of life. Trapping the molecules in the "eutectic" phase of ice leads to highly concentrated solutes trapped in a small volumes of liquid, surrounded by the solid water. This may effect have helped to overcome a sparsity of molecular components, and also provided a quasi-cellular environment that helps to fight parasitic nucleic acids. The polymerase ribiozyme itself functions slower, but is much more stable, at this low temperature. The result is that it can incorporate more rNTP monomers in total.


1/7/2019
Molecular computation of solutions to combinatorial problems
https://science.sciencemag.org/content/266/5187/1021.long
This paper outlines a method of using biomolecules to find out if there is at least one path through a network which passes through every node exactly once.

It encodes each edge between two nodes as a single strand of DNA, which can bond in complementary ways to other edges to form paths.

The process is as follows
1) Generate random paths through the network by mixing all the edge strands together.
2) Amplify those paths which start at the "beginning" node and end at the "end" node by adding  a single strand complementary to the beginning and the end marker which is linked to an object which encourages replication.
3) Use agarose gel to pick out those sequences which are the right length to be equal to the number of nodes in the network. Amplify the result.
4) Remove one of the strands so you have single strand DNA. Add a single strand corresponding to one of the nodes which is attached to a magnetic bead. Attract the ones which have that node, discard the rest. Repeat for every node in the network. This assures that every node is hit by the path.
5) Amplify the result.


This method can, in principle, implement 34 x 10^19 (irreversible) operations per joule. Existing supercomputers (1994) are far less energy-efficient, executing at most 109 operations per joule.

Transcription reinitiation by recycling RNA polymerase that diffuses on DNA after releasing terminated RNA
https://www.biorxiv.org/content/10.1101/684738v1
Previous modelling of the transcription process considered that it finishes with the separation of the produced RNA strand and all the transcription protein-machinery separating at the same time. However, the experimental results obtained show that the RNA polymerase actually stay attached to the DNA for more than a minute instead of the expected milliseconds. During this stage, named by the authors "recycling phase", the polymerase diffuses in 1D along the DNA strand searching for a new start codon.

The authors calculated the binding time of the polymerase and its diffusion constant across the DNA strand observing the PIFE effect using single molecule fluorescence microscopy. PIFE stands for "Protein-Induced Fluorescence Enhancement" and involves observing the variation of fluorescence produced by the interaction between the protein and fluorophore in the strand.

This new knowledge on transcription machinery will help to improve RNA expression models and the design of physical systems that can harness the polymerase diffusion across DNA strands.

DNA methylation GrimAge strongly predicts lifespan and healthspan. https://doi.org/10.18632/aging.101684
Methylated DNA (DNAm) in promoter regions often reduces translation rates. The authors used measurements of DNAm levels in thousands of elderly humans to construct an epigenetic clock, DNAm GrimAge: an estimator of lifespan, time to cancer, and time to heart disease. This was achieved in two phases; the DNAm levels were used to as estimators of plasma protein levels, and the constructed protein levels were used to calculate the composite biomarker GrimAge. GrimAge has good predictive ability.

Terminator-free template-independent enzymatic DNA synthesis for digital information storage.
https://www.nature.com/articles/s41467-019-10258-1
DNA has been hyped as a highly-promising storage medium due its unparalleled information density as well as a shelf life that dwarfs that of all the optic and electronic storage mediums currently known. But it has the problem that the information retrieval is highly complex as well as the fact that the synthesis methods currently available are limiting with regards its usage. In the present paper, Church and collaborators propose a method consisting of using a template-independent polymerase that can add nucleotides to an existing strand depending on given chemical conditions (which include competition with other enzymes in order to limit the process). The process -called transition- encodes the information supplied by the user and it is random in nature, but the probabilities of each event depend on the conditions in a known way. With the help of some scaffold sequences that assist with sequence alignment, the output sequences can be read and the different environment can be traced back. The authors use a codec that they claim gives an optimal trade-off between information density storage and fidelity measurements.

DNA Microscopy: Optics-free Spatio-genetic Imaging by a Stand-Alone Chemical Reaction
https://www.sciencedirect.com/science/article/pii/S0092867419305471
DNA microscopy – a technique to reconstruct special distribution of mRNA transcripts within tissues with full sequence information.

The authors propose an approach in which DNA sequences are amplified from mRNA, and can subsequently diffuse out of the cells in which they were made. One two different mRNA sequences are produced nearby, the DNA sequences can concatenate; the frequency of concatenation indicates the proximity of cells producing the transcripts.

During each amplification, a unique sequence is added within the gene to mark individual connecting events. After sequencing the cDNA/connected cDNA from the tissue, the inserted sequence is used to reconstruct the relative original position of each mRNA.

Positive and negative circuits in dynamical systems
https://www.worldscientific.com/doi/abs/10.1142/S0218339098000054
The following two statements, relating long-time dynamics of a system of ordinary differential equations and  the underlying feedback circuits, are proved:

a) the existence of a positive feedback circuit is a necessary condition for the existence multiple stable equilibria,

b) the existence of a negative feedback circuit, of at least length two, is a necessary condition for the existence of a stable periodic orbit.

Stochastic thermodynamics and modes of operation of ribosome: A network theoretic perspective 
https://arxiv.org/abs/1906.08154
The authors present a model of ribosome-based translation of proteins in which all steps are treated as microscopically reversible, in principle allowing a thermodynamic analysis. However, the design of the model is problematic, since the binding of correct and incorrect tRNA is only resolved as separate states after the polypeptide bond has formed.



15/4/2019
Single Particle Tracking and Super-Resolution Imaging of Membrane-Assisted Stop-and-Go Diffusion and Lattice Assembly of DNA Origami
https://pubs.acs.org/doi/10.1021/acsnano.8b04631
In this paper, the diffusion of DNA origami object on supported lipid bilayer was reversibly stopped by changing the salt concentrations in the buffer. The structures were let to diffuse during the assembly phase and stopped during the imaging phase for a DNA PAINT imaging which revealed the higher order assembly of monomers.

RNA-Capturing Microsphere Particles (R-CAMPs) for Optimization of Functional Aptamers.
https://onlinelibrary.wiley.com/doi/10.1002/smll.201805062
Aptamers are nucleic acid chains that are able to recognise and bind a specific molecule or motif. A process called SELEX is used to find aptamers with specificity for a molecule of interest. This process consists in several time-consuming cycles where a library of nucleic acid sequences is exposed to the molecule of interest. The sequences that recognised the molecule are PCR amplified, progressively enriching the solution in the specific aptamers. The time investment required for this process is even higher when searching for RNA aptamers or using several buffer conditions.

A variation of the SELEX method is introduced in this work. Primer-functionalised microspheres are used to express a library of DNA sequences in their surface. By using emulsion PCR, you obtain a collection of DNA sequences attached to the microspheres, with each microsphere coated with copies of a single sequence. Each of these sequences also contain a T7 promoter and an "anchor" domain. RNA aptamers are produced from these sequences during a transcription step, while keeping bound to the microsphere sequence by the "anchor" domain. These RNA-DNA aptamer microspheres allow easy testing and purification of both RNA and DNA aptamers in only two steps, saving a significant amount of time. The method was used to check the variation in fluorescence for different random mutations in the "Broccoli" RNA aptamer in buffer and with high PEG concentrations. The method is reported to produce a sequence enrichment >90% in only one cycle.

Marginal and conditional second laws of thermodynamics
http://arxiv.org/abs/1611.04628
When dealing in thermodynamics, it is often assumed that the system of interest is so weakly coupled to systems of less interest (e.g. the rest of the universe) that we can consider each part to be isolated. Isolated heat baths and chemical reservoirs are the bread and butter of thermodynamics. These constructions are useful when we want to derive results such as the 2nd law of thermodynamics.

The authors of this paper present a formulation of thermodynamics that describes a strongly-coupled, bipartite system, not in the language of isolated baths, but from a consideration of the causal relationships between the sub-systems. The authors derive second law-like relationships for the total, marginal, and conditional dissipations of the system.


1/4/2019
Principles and Applications of Nucleic Acid Strand Displacement Reactions
https://pubs.acs.org/doi/full/10.1021/acs.chemrev.8b00580
An extensive review paper on DNA strand displacement reaction in the Chemical reviews by Friedrich C. Simmel and Bernard Yurke. With more than 400 references, it covers from the biophysics of strand-displacement reaction to state-art DNA circuits, nanodevices and nanostructures

Mechanisms for achieving high speed and efficiency in biomolecular machines. 
https://www.pnas.org/content/116/13/5902
"Our model explores parameters of evolution and synthetic design: not just what is, but what could have been."

In 'Mechanisms for achieving high speed and efficiency in biomolecular machines', Wagoner and Dill study the efficiency and speed of biomolecular machines by exploring a parameterised free energy landscape. The authors split one cycle of the biomolecular machine into an arbitrary number of sub-steps that alternate a conformal change in which chemical work is done on the system, followed by a mechanical step in which the system does work on the environment. By parameterising the free energy barriers and the free energy difference between sub-steps the authors reach a number of interesting conclusions.

1) To optimise the speed of a cycle, decrease the forward barriers, rather than  the reverse barriers, for a given free energy change.
2) The fastest cycles are often those in which the forward barriers are all equal.
3) The speed is optimised when the intermediate conformation acts as an energy 'store' for the mechanical step. This amounts to having to provide free energy for this intermediate conformation.
4) Many substeps are faster than fewer substeps at the same efficiency. This redistributes the barrier heights. Many small hills are easier to overcome than one large hill.
5) Biomolecular machines like Myosin and Na-K ATPase are fast and efficient. They both feature numerous substeps. RNAP is slow for the same efficiencies as the previously mentioned machines.

Fluctuation Theorem of Information Exchange between Subsystems that Co-Evolve in Time
https://www.mdpi.com/2073-8994/11/3/433/htm
In 2012 Sagawa and Ueda showed how the second law of thermodynamics for a subsystem is modified by the effects by the state of a second subsystem. This paper is an attempt to generalise the results of Sagawa and Ueda to the case where the second subsystem changes in time. However, this paper simply recovers the standard second law of thermodynamics of the nonequilibrium free energy of the  joint system. The second law of thermodynamics has be modified to include information flow in cases where both subsystems change with time in e.g:
https://journals.aps.org/prx/abstract/10.1103/PhysRevX.4.031015
https://iopscience-iop-org.iclibezp1.cc.ic.ac.uk/article/10.1088/1742-5468/2014/02/P02016/meta


18/3/2019
Triangular DNA origami tilings 
https://pubs.acs.org/doi/abs/10.1021/jacs.8b10609
In this paper Qian and collaborators developed a new algorithm that allowed them to implement regular triangular DNA shapes into DNA origami (in opposition to the squared shapes that up to the present moment have been the most commonly available shape in 2D origami). In addition to the tilings' design, they were also able to staples that allowed them to assemble the tilings in discrete 3D shapes (both spheroid and hexagonal pyramid-like), as well as in 2D structures (both discrete and periodic). The kind of edges that are initially in the tiles are the only variable that determine this assembly in a predictable manner.

Direct evaluation of dynamical large-deviation rate functions using a variational ansatz
https://arxiv.org/abs/1903.06098
This paper presents a method to calculate the large deviation rate function of a time-extensive observable of a continuous time discrete state Markov chains by simulating a modified Markov chain. The problem with trying to calculate the rate function from simulating a stochastic process is that the probability of rare events is hard to calculate because they do not often occur in the simulation. Therefore, if it is possible, it would be advantageous to simulate a different stochastic process in which these rare events are less rare and then transform the probabilities calculated back into probabilities in the original process. In this paper a parameterisation of a modified process is chosen and then the parameters are optimised to minimise the error in the calculated rate function. The authors show that, in their method, if a good choice of modified process is chosen then the rate function can be calculated exactly; otherwise a bound on the rate function can be calculated.

Dynamically Programmed Switchable DNA Hydrogels Based on a DNA Circuit Mechanism
https://onlinelibrary.wiley.com/doi/full/10.1002/smll.201900490
DNA strand displacement reactions, are, as we know, a useful tool for cascading signals inside DNA networks. Commonly, the input and outputs of these networks can only be appreciated in the nanometric scale; however, these outputs can be effectively used to trigger macroscopic processes.

In this paper, a DNA network output is employed as the trigger for the phase transition, from solid to liquid, of a DNA hydrogel. This DNA hydrogel is composed by an amalgamation of PEGylated gold nanoparticles, and cross-linked DNA strands. The cross-linking nodes express free toeholds, complementary to the network output, which mediate the destruction of the cross-linked structure, freeing the gold nanoparticles in the process.

This approach has been applied to create an ATP biosensor, using an ATP aptamer as inhibitor of the strand displacement network. With a lower limit of detection of a concentration of ATP as small as 50 µM, the gel experience the phase transition to liquid, producing an eye-perceptible signal.


4/3/2019
A “time-frozen” technique in microchannel used for the thermodynamic studies of DNA origami 
In this paper, the authors have blown hot air onto a microfluidic channel to create a spacial temperature profile. Then they flow in the DNA origami folding mix with slow rate which converted the spacial temperature gradient to a temporal gradient. They have also shown that they can fold the origami as well as observing the folding in real-time with a fluorescence microscope. 

Hachimoji DNA and RNA : A genetic system with eight building blocks http://science.sciencemag.org/content/363/6429/884
In this work, Benner and collaborators have demonstrated that new additional pairs of nucleobases can form base pairings akin to those in Watson-Crick pairings. These nucleobases can be part of nucleotides  that can be integrated into biologically functional DNA and can be transcribed (as they demonstrate here by transcribing a 8-nucleotide variant of a spinach fluorescent aptamer). The relevance of this discovery lies in the experimental demonstration that genetic information processing can be performed in other polymers rather than those we know, as well as the new possibilities in terms of fine tuning of free energy landscapes that adding new nucleotides poses for DNA nanotech.

Geckos Race Across the Water’s Surface Using Multiple Mechanisms
Locomotion at the air-water surface has evolved in many species and is achieved by different mechanisms that are relevant on certain length and weight scales. Smaller animals rely on surface tension to provide thrust and buoyancy. Larger animals resort to slapping the water's surface to generate lift while delivering thrust via paddling with their tail. Meso-scale geckos employ a combination of these mechanisms and can run across water at speeds that are comparable to their speeds across land. A gecko's skin is superhydrophobic, which contributes to a reduction of drag, due to the body and tail, while hydroplaning.


18/2/2019
Cascade of transitions in molecular information theory
https://iopscience.iop.org/article/10.1088/1742-5468/aaddaa
This paper considers a model of a cell and environment where the environmental state and the cell response are random variables. For each state the cell gains an amount of free energy that depends on the response. There is also a free energy cost to the cell of correlating its response to the environment of the mutual information between the state and the response. The cell sets its probability distribution of responses to maximise the expected free energy gain. If the cost is weighted highly against the gain, then the cell is in the non-coding regime where it is optimal for the machine to always give the same response. For lower weighting of the cost it is optimal for the cell to respond specifically to the environment state. The authors find three classes of asymptotic behaviour for the boundary between these two regions.


Autonomously designed free-form 2D DNA origami
The authors have developed a platform for fully-automated staple sequence generation program for 2D origami objects. http://perdix-dna-origami.org/ It looks straightforward.

Two Synthetic Replicators Compete To Process a Dynamic Reagent Pool
https://pubs.acs.org/doi/10.1021/jacs.8b12077
Self-replicators are chemical species capable of catalysing the formation of an identical species (replica) from some chemical building blocks. When the same building blocks are used by more than one self-replicator, these have to compete. In the present paper, the authors analyse the dynamics that arise from this competition, when building blocks are being simultaneously generated by chemical reactions and consumed by the self-replicators.

Analysis of the network shows that building blocks tendency to form one or the other replicator can be tuned by varying the steady-state concentration of the building blocks. If the concentration value is between the building blocks dissociation constants values of each self replicator (Kd1<[B.Block]<Kd2) it will favour the formation of the self replicator with the lowest dissociation constant (Kd1).

However, the difference between the formation speed of the self replicators remains as the strongest way of selective discrimination (kinetic discrimination). 

4/2/2019
Simulating the Monty Hall problem in a DNA sequencing machine
DNA computation has great computation power since each single molecule in the solution can realize an operation, thus having a great level of parallelization. However, the applicability of these computational systems to real problems is questioned.

In this paper, the authors apply a DNA system to solve the Monty-Hall problem. This problem presents a scenario where, after making a choice between two incorrect and one correct concealed options, one incorrect is revealed and the possibility of exchange the choice is given. The problem is encoded as two different sequences (wrong and correct) located after 3 different priming sequences. These priming sequences are used to sequence whichever sequence is near it, so it is possible, after sequencing using one priming sequence, to obtain in parallel all the different combinations of making one particular choice. This simple application makes a good example of what more complex systems, encoded in DNA, are able to achieve.

Efficiency fluctuations in microscopic machines
https://arxiv.org/abs/1901.05805
Previously, in https://journals.aps.org/pre/abstract/10.1103/PhysRevE.90.052145, it was shown that the long-time fluctuations of the efficiency of small heat engines display some universal features that are independent of the specific details of the engines. In particular, the most likely efficiency is the macroscopic efficiency and the least likely is the reversable efficiency. In this new paper it is shown that engines with a continuous state space can violate the assumptions of the previous universal theory.

Information-based autonomous reconfiguration in systems of interacting DNA nanostructures
https://www.nature.com/articles/s41467-018-07805-7
Rectangular DNA origami objects with encoded meta toehold can undergo DNA tile displacement.

Central dogma rates and the trade-off between precision and economy in gene expression
https://www.nature.com/articles/s41467-018-07391-8.pdf
Natural genes prefer to have low rate of transcription and high translation rate rather than opposite combination.

Something has to give: scaling combinatorial computing by biological agents encoding NP-complete problems 
https://royalsocietypublishing.org/doi/full/10.1098/rsfs.2018.0034
The present paper is a review that presents an alternative biologically-based computing platform called on-chip network computing. Here, a microfluidics chip has built into it the nodes of a graph corresponding with a combinatorial NP problem. A biological agent (perhaps either a filamentous cytoskeleton protein or a microorganism) can track all the possible solutions throughout the graph, either in serial mode like a conventional computer, in parallel, or - if the computing agent is a microorganism - multiplying exponentially covering the whole graph.

The later approach in principle, when based in sheer power (not using heuristic algorithms) can overcome current limitations faced by conventional silicon computers. This approach trades time limitations with space limitations, has an in principle lower energy consumption per computation, and allows the user to track in real time how the graph tree is explored by the agent. However, current optical systems still are not able to trace in real time how these graph trees are explored at the maximum theoretical information density allowed by the chip, thus limiting the readout capabilities and real performance of these systems.

Shortcuts to Thermodynamic Computing: The Cost of Fast and Faithful Erasure 
https://arxiv.org/abs/1812.11241 
This work presents an analysis of thermodynamic protocols that achieve exact transformations of probability distributions in finite time. In the context of overdamped 1D Langevin Dynamics, the authors  use the formalism of "counterdiabatic protocols" to make general statements about the scaling of optimal operations with time and system size, and then to consider a specific class of protocols for the classic problem of switching or setting a bistable system (a bit). The authors show  that arbitrarily accurate erasing is possible in finite time. The authors then discuss how the robustness of information storage is related to the cost of the information-processing operations.


14/1/2018
Cation-Activated Avidity for Rapid Reconfiguration of DNA Nanodevices
https://pubs.acs.org/doi/10.1021/acsnano.8b04817 
Dynamical DNA structures' conformational changes are currently limited by their response times. The common approach to produce these changes is DNA strand displacement which takes, in the best cases, minutes. This paper propose an alternative approach that produces responses on the time scale of milliseconds: changes of ionic strength in the medium. The approach harnesses the fact hybridization of that small overhangs (i.e. single strand domains in the DNA origami structure) is heavily dependent of the cation concentration of the buffer.  

To test the mechanism, the authors designed a DNA origami hinge with small complementary overhangs on its interior surfaces. While the hinges remained open at low cation concentrations ([Mg2+]<10mM), they would bind at higher salt concentrations, closing the hinges in milliseconds. When the cation concentration was reduced, the hinges were able to open again.

A statistical mechanical model for this behaviour is also included in the paper, where the partition function of open/closed hinges can be predicted from the number of overhangs, its length and the ionic force of the medium. The results of this paper provide a new fast actuation mechanism for Dynamical DNA structures, which can be vital for functions where speed is vital, like controlling enzymatic reactions.


The origins of quantum biology, Johnjoe McFadden and Jim Al-Khalili
A historical review of the observation, and surrounding philosophy, of quantum effects in biological systems since the dawn of quantum mechanics. The authors chart a century of debate featuring contributions from Bohr, Heisenberg, Schrödinger, Jordan, Hopkins, Watson, Crick, and Frohlich. Coherence, and the resulting quantum mechanical effects that can be observed, are most often attainable only in small, cold systems. Living systems tend to be large and hot, and, therefore, decoherence  leads to the dissolution of observable quantum effects - we observe a classical system. In some cases, however, quantum mechanical phenomena do scale up to affect macroscopic features, or behaviours, of the system. Experimental evidence suggests that quantum mechanics plays a decisive role in avian magnetoreception, olfaction, photosynthesis, and electron transfer in biological molecules such as proteins. The authors note that progress made in the field of information theory applied to non-equilibrium quantum mechanics may have some power to explain the operation of systems in highly noisy environments, as classical non-equilibrium thermodynamics has demonstrated in recent decades. 


3/12/2018
Emergent behavioural phenotypes of swarming models revealed by mimicking a frustrated antiferromagnet
http://rsif.royalsocietypublishing.org/content/12/111/20150520
If you put swarming animals in a circular channel they will swarm cyclicly, choosing either clockwise or anti clockwise at random. If you put two circular channels next to each other, sharing a window then the two channels will swarm so that at the window, the swarms are going the same way. This corresponds to clockwise next to anticlockwise. Thus the system behaves like an anti ferromagnet. You can therefore study frustrated antiferomagnet systems using hexagonal/triangular spin lattice systems. You can use this to construct logic gates.

Work as a Memory Record
The traditional explanation of the survival of the second law of thermodynamics in the presence of a "Demon" that can form measurement and feedback to rectify fluctuations and extract work from an equilibrium system is that the process creates a record in a memory that must be erased. This erasure requires work, and is therefore deemed to "save" the second law. In this article, the author asks the question of what happens if the work reservoir itself is the location of the memory record, and therefore cannot be reset. From the traditional perspective, this setting seems to be a problem We feel that this misses the point - resetting is not necessary to preserve the second law in the context of measurement and feedback. This fact would be clearer if the devices considered in the paper were more explicit. 

A CRISPR–Cas9-triggered strand displacement amplification method for ultrasensitive DNA detection
https://www.nature.com/articles/s41467-018-07324-5
The authors achieved isothermal amplification of target DNA using the sequence-specific nicking endonuclease activity of Cas9. Adding a primer pair enables the extension of sense and antisense strands by DNA polymerase followed by the exponential amplification of each strand. The sensitivity is tens of atto molar with an ability to distinguish single nucleotide polymorphism.

Receptor crosstalk improves concentration sensing of multiple ligands
https://arxiv.org/abs/1810.04589
A cell can detect the concentration of two different ligands in its environment using two different cell surface receptors. In theory the cell could use downstream processing to find the maximum likelihood concentration using the length of the times for which the receptors are bound. One would assume that the sensing is most accurate when each receptor can only bind to one of the ligands but this paper shows that in some cases having a non-zero binding to both receptors is beneficial.

Improving the Performance of DNA strand displacement circuit via shadow cancellation
https://pubs.acs.org/doi/abs/10.1021/acsnano.8b07394
Leakage in catalytic strand displacement networks reduces the signal to noise ratio, thus limiting the depth (amount of steps) of the network. Leakage is a difficult problem to tackle, since it requires full knowledge of the network architecture and the possible leakage routes. This paper proposes an "architecture-agnostic"  strategy called shadow cancellation. This strategy consists of duplicating the proposed network. This duplicated, or "shadow", network running in parallel will have the same architecture, and thus, the same leaking rate. The leaking of both networks can react with "cancelling complexes" with a 1:1 stoichiometry, resulting in the removal of the leaking produced strands. In this work, the authors implement this strategy in a two-seesaw gates network with cross-catalytic feedback. They test the effect of the addition of different ratios of network/shadow network (1/0.9, 1/1 and 1/1.1). They found 1/1 to be the optimum condition to cancel noise without delaying the output signal. The signal-to-noise ratio obtained after the addition of the 1/1 shadow network has an improvement of 730% over the original network. According to the results, this strategy poses as a quick way  to diminish the noise in a multi-step network without changing the architecture of the network or by adding additional domains.

AND

This paper proposes a novel strategy called shadow cancellation. The strategy involves the use of "shadow reactions" with the same architecture as the reaction that we want to design and implement (in this paper they implement the authors couple to a signal amplifier consisting of two seesaw gates in which the input of the second is the output of the first).  Leak reactions can happen when the fuel displaces the output/fuel before the input generating a waste. This trouble gets mitigated through the action of  of cancellation complexes C1 and C2, that sequester the excess of OA1 and OB1 for C1 and OA2 and OB2 for C2 (each Cx complex blocks the outputs of each x seesaw gate of the amplifier and the shadow circuit). The presence of this shadow cancellation leads to a circuit with dynamics that resemble sigmoidal curves and in order to properly work needs the amplifier and the shadow circuit to be in the same concentration. This system might look a bit complicated as an strategy to improve the performance of a DNA reaction network (other anti-leak strategies like using 4 way- junctions and high energetic were described previously and are much simpler)


19/11/2018
Selection strategies for randomly distributed replicators 
https://arxiv.org/abs/1711.04350
Zadorin and Rondelez address the question of how the co-encapsulation of multiple separate replicators within single volumes might influence the evolution of a population. Through a combination of theory and numerical approaches applied to simple models, they demonstrate that the general effect of co-encapsulation is to slow down the evolutionary dynamics by a factor 0 < g(lambda) < 1, where lambda is  the average occupancy of individual compartments. The function g(lambda) is determined by the particular manner in which resources are utilised within a compartment. They argue that this slowdown can be relatively mild in certain circumstances, and even claim that co-encapsulation of multiple replicators can improve the evolutionary search efficacy at a fixed budget of replication volumes.

Unified framework for the second law of thermodynamics and information thermodynamics based on information geometry
https://arxiv.org/abs/1810.09545
The transition probabilities of a stochastic process form a manifold. This paper shows that the second law of thermodynamics in stochastic thermodynamics can be derived by finding the minimum distance between a point on the manifold and a point on a submanifold of only the reversible dynamics.  In a system of two random variables it has been previously shown that there is a tighter bound on the entropy production of a single variable than the second law of thermodynamics applied to the joint system. This tighter bound is called the ‘second law of information’ and can be derived by finding the shortest distance to the reversable manifold of one of the variables.

DNA nanodevices controlled by entropic linker domains
https://pubs.acs.org/doi/10.1021/jacs.8b07640
In this work resulting from a collaboration between the Ricci and De Greef labs, the authors present two kinds of DNA devices (an ATP recognizing aptamer and a DNA clamp designed to recognize an input strand) incorporating intrinsically entropic domains that do not interact with the input but take part in the dynamics of the devices. For these two devices they test different lengths of entropic domains and they observe that the affinity of the device for the substrate/input decreases linearly with the size of the disordered domain. This mechanism could offer new possibilities for the design of thresholding mechanisms for DNA circuits that work with small differences in concentrations.

Andrew King (Swansea University) Sociality, heterogeneity, organisation and leadership in animal societies. (Talk)
The behaviour of leaf cutter ants crossing a narrow bridge can be modelled using a hierarchy of importance to determine who steps aside and who carries on forwards. This hierarchy is broadly [ants returning with leaves]>[outgoing ants]>[ants returning empty handed]. The exceptions to this are ants returning empty handed directly behind ants returning with leaves who can follow through before the outgoing ant steps back onto the bridge.

The behaviour of sheepdogs herding sheep can be modelled as a two mode process of aggregating and pushing. The aggregation mode uses circular or oscillatory motions around the sheep, while the push mode is a straight line. Thus you get predictable paths. This suggests you could design robots to aggregate active particles, something which the group is considering.

Thermodynamics of stochastic Turing machines
The authors study three types of Turing Machine (TM): A logically irreversible TM (the input state cannot be uniquely defined by the output state – consider an AND gate), a logically reversible TM (the input state can be uniquely defined given the output state), and a stochastic logically reversible TM (each computation in the operation of the TM can proceed with a forward rate, or a backward rate – the ‘direction’ of the computation is no longer deterministic, it can operate in reverse).

In each case the TM operates by iterating a process of reading the input tape, completing a computation according to a set of general rules, writing to an output tape and overwriting the input, and then moving to an adjacent site or remaining situated on the tape. For any input tape, it is impossible to determine after how many iterations the TM will come to completion without just letting the system run. This is known as the halting problem in computation theory. As a result, the state space that the TM traverses through is, in general, extremely large, and potentially infinite. However, given that the TM only moves between adjacent sites on each step of the computation, the trajectory traced by the TM can only make nearest-neighbour, or one-step, transitions on each iteration. Therefore, the evolution of the probability distribution that describes the occupancy of states of the stochastic TM can be described by a one-step Master equation. Simple birth-death processes, in which the population can increase or diminish by 1 or 0 on each step, are also described by such a model.

For the stochastic TM, the forward and backward rates of transition are defined by the principle of detailed balance, with an, on average, linear driving potential. As a result, the Master equation can be approximated by a Drift-diffusion Focker-Planck equation, and solved for a diffusivity and drift velocity.

The authors demonstrate that under quasistatic conditions the logically-reversible stochastic TM can also operate thermodynamically reversibly. This is a special case; logical reversibility does not imply thermodynamic reversibility. In the thermodynamically reversible regime, the total integrated entropy of the computation is, however, non-zero, and is proportional to the log of the number of steps taken.

Importantly the stochastic TM operates error-free at finite entropy production. The model does not allow for the TM to make any error during computation, only for the ‘correct’, linear trajectory to be explored with a propensity to take some backward steps. This model is essentially a relaxation process. 

Sequence-programmable covalent bonding of designed DNA assemblies
The authors present a mechanism for linking proximal thymidines to make DNA origami objects survive against no-salt environment and attack from many nucleases. 

The entropic force generated by intrinsically disordered segments tunes protein function
The entropic force from an unstructured polypeptide chain depends on the length of the unstructured domain. Therefore, by tuning the length of the unstructured domain, the free-energy difference between different states of the protein upon binding changes which can be used to tune the function of the protein by preferring allosteric activation or inhibition.

DNA Strand Buffers
This paper proposes a simple, yet effective, DNA strand displacement system that can act as a buffer. The system couples a strand (buffered strand) of any strand displacement reaction with another reversible strand displacement reaction. This reversible reaction remains in equilibrium by sequestering the buffered strand and liberating more while it reacts, maintaining its concentration, i.e. its chemical potential, constant. When the components of the reversible reaction are present at high concentrations, they can buffer disturbances orders of magnitude bigger than the buffered strand concentration. The speed of the recovery is entirely determined by the speed of the reversible reaction, which in turn is controlled by toehold lengths. Additionally, several buffering systems can be coupled in parallel without cross-talking, allowing the creation of complex systems that can operate over longer times.

22/10/2018
Towards a bioelectronic computer: A theoretical study of a multilayer biomolecular computing system that can process electronic inputs.
https://www.mdpi.com/1422-0067/19/9/2620/pdf 
This paper shows a theoretical study on how, using the pH-sensitive i-motif developed by Idilli and collaborators, a DNA reaction network circuit could theoretically detect an input based on a voltage change. This electrode-induced voltage change would activate a catalytic cycle that acts like a while-loop. The ammount of output produced by the loop can later can be fed into another layer consisting of four different thresholders that translate the analog input into a discreet number of outputs. These outputs can later on can be feed into a DNA-based finite state machine. The paper suggests this could open new possibilities with regards control of DNA nanomachines, but certainly the real implementation of such a device is not a trivial task at any of the layers involved.

A RNA producing DNA hydrogel as a platform for a high performance RNA interference system
https://www.nature.com/articles/s41467-018-06864-0
A hydrogel is built from DNA encoding a sequence for siRNA. Its interference ability was tested at multiple levels: cell lysate, and with live cells. Up to 8 times better silencing effect was observed due to stability of the a gel network, the high transcription efficiency of the plasmid in the gel phase, an elongated promoter region, the gel size, and the higher local concentration of I-plasmids in the I-gel.

Energy consumption in chemical fuel-driven self-assembly
https://www.nature.com/articles/s41565-018-0250-8 
This perspective paper propose to settle a formal terminology for fuel-coupled self-assembly systems according to its interaction with the fuel. They specially focus in what they denominate "Driven self-assembly". These are the self-assembly processes, coupled with fuel-waste conversion, that can store energy in the form of a high-energy aggregate species when being constantly supplied with a fuel. When the concentration of fuel reaches an equilibrium, these high-energy aggregates collapses, returning all the species to their original concentrations in the equilibrium .  For the out-of equilibrium shift in concentrations to take place, the fuel consumption rate must be significantly faster than the waste production. The ratio between these rates is directly related with the energy storing capacity  of the system while consuming fuel. This storing capacity is relevant to determine the ratio of species out of the equilibrium when coupling 2 or more systems capable of consuming the same fuel. A higher capacity to store energy can become sufficient to make a thermodynamic unstable aggregate from one system dominant over a more stable aggregate with less storing capacity.

Arcsine Laws in Stochastic Thermodynamics
https://journals.aps.org/prl/abstract/10.1103/PhysRevLett.121.090601
For stochastic Markov processes, it is more likely that a given trajectory spends extended periods of time above or below the average value than it is to repeatedly cross the average value. This can be understood intuitively by considering that any trajectory is truncated; it is considered over a finite timescale. For an infinitely long timescale we would expect that a trajectory would on average spend an equal length of time above or below the average. However when we truncate this we effectively take portions of this infinite trajectory which start when the trajectory is an average value and then run for a finite fixed length of time. Combinatorially there are only a limited number of trajectories segments which repeatedly cross the average without deviating far from it. There are many more trajectories where the trajectory moves far from the average and has much larger rates of change. While these are both above and below the average, the truncated segment only gives one of these.

Quantifying Molecular Forces with Serially Connected Force Sensors
https://www.biorxiv.org/content/early/2018/08/31/405761
Murad and Li present a theoretical analysis of the application of the recently-proposed tension gauge tether (TGT) in molecular force spectroscopy. They highlight a major issue with naive application of single TGTs - namely that a single fluorescence measurement cannot distinguish between multiple force application histories. They argue that using two serially connected TGTs (G and R) can solve this problem, since the ratio of rupture within a small time dt, dG/dR is well-defined function of the force. In effect, a number of factors that induce uncertainty cancel out in this approach.


10/9/2018
DNA-Guided Plasmonic Helix with Switchable Chirality
https://pubs.acs.org/doi/10.1021/jacs.8b06526
The authors design and test a helical DNA origami structure capable of changing its chirality. The structure is produced by the binding of several V-shaped DNA building blocks functionalized with gold nanorods. By two strand displacement reactions, these V-blocks can be inverted, changing the sense of rotation of the helix, and therefore the organization of the gold nanorods. This allows the dynamical change of the optical properties of the solution where the structures are dissolved.

Effect of sequestration on signal transduction cascades https://febs.onlinelibrary.wiley.com/doi/full/10.1111/j.1742-4658.2006.05105.x
In this paper the authors discuss about the working of transduction cascades and the different means through which they can reach ultrasensitivity,  focusing in zero-order ultrasensitivty. They argue that, in the saturation conditions in which push-pull networks work physiologically and given the high affinity of the enzymes that form the catalytic pair in push-pulls and their sensitivity to product concentrations, sequestration of the push-pull substrate by the catalyst can appear and break the conditions required for zero-order ultrasensitivity as well as other phenomena such as sustained periodic waves. Despite this situation, it is argued also that this sequestration, while detrimental for the aforementioned mechanism, might be crucial in order to allow transduction cascades to feature properties such as time-delay and crosstalk resilience and time-dependent signal integration.

Visual and modular detection of pathogen nucleic acids with enzyme–DNA molecular complexes
https://www.nature.com/articles/s41467-018-05733-0
This paper detects pathogenic nucleic acids with a two-step procedure. 1. activation of Taq polymerase by triggering the release of an inhibitory aptamer with a strand-displacement reaction by pathogenic nucleic acids. 2. Elongation of partial DNA hairpin structures with biotin modified bases to capture horseradish peroxidases that produce colorimetric signal, indicating the presence of active Taq and hence the pathogen.

Non-equilibrium odds for the emergence of life
https://arxiv.org/abs/1705.02105
In functional proteins the different amino acids are present in approximately equal proportions but when produced in equilibrium the amino acids with higher free energy of formation are much less prevalent. This paper argues that in an out of equilibrium setting the proportion of the rarest amino acids can be increased compared to in equilibrium. It also shows that when a solution of monomers is far from equilibrium the probability of longer polymers is increased by many orders of magnitude compared to when it is in equilibrium.

Conservation Laws and Work Fluctuation Relations in Chemical Reaction Networks 
https://arxiv.org/abs/1805.12077
The authors present a detailed formalism for the systematic analysis of the thermodynamics of stochastic chemical reaction networks. In particular, they address the fact that conservation laws restrict the evolution of the system to certain conservation classes; if the initial probability distribution is spread over several of these classes, one needs to be careful to recover expected fluctuation relations etc. These conservation laws, and those that are broken if the system is coupled to external chemostats, provide a natural basis through which to analyse the system.

20/8/2018
Renewable time-responsive DNA circuits
https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.201801470
This paper describes the simulation and dual-rail logic implementation of two types of Boolean logic gates (1-input-1-output NON gate and a generic 2-inputs-1-output gate). These gates are implemented using non-catalytic DNA reactions in which the triggering of the gate creates a time-responsive reaction intermediate that can be restored to the initial state through the injection of recovery strands that sequester the input strands. This strategy is proposed as an step to implement more complex functionalities in DNA circuits akin to those present in cellular regulation.

Energy Dissipation and Information Flow in Coupled Markovian Systems
https://arxiv.org/abs/1807.00116
In a setting with a ‘system’ that is a Markov chain with transition probabilities that depend on the state of an ‘environment’ that is also a Markov chain a quantity called the nostalgia can be defended, which is the difference between the information the state of the system has about the previous environmental state and the information it has about the next environmental state. The nostalgia is bounded from above by the dissipation of the system. This paper shows that when there are two environment states and two system states the nostalgia to dissipation ratio is bounded from below by a function of only a single rate associated with the environment and a single rate associated with the system.

Self-replication of DNA by its encoded proteins in liposome-based synthetic cells
Φ29 replication proteins are synthesized from the DNA template by PURE system. Φ29 replication proteins amplify their own template thereafter. This cycle was Implemented in liposome-based synthetic cell models

Backbone-free duplex-stacked monomer nucleic acids exhibiting Watson–Crick selectivity
http://www.pnas.org/content/early/2018/06/28/1721369115
The paper describes the X-ray structure of high concentration (~1.5 M) mixtures of NTPs.
The nucleotides are found to assemble in the form of liquid crystals, in the same way as DNA duplexes when mixed with Watson-Crick complementarity (except for rATP + rUTP). Even when the current data cannot distinguish local structural motifs, the authors claim that the autocatalytic formation of liquid crystals, even when NTP's have "high-organization-freedom", is produced by Watson-Crick base pairing.


30/7/2018
Single-Atom Demonstration of the Quantum Landauer Principle 
https://journals.aps.org/prl/abstract/10.1103/PhysRevLett.120.210601
The authors study the manipulation of a bit connected to a finite-sized "thermal" environment. The bit consistents of two electronic states of a calcium ion; the environment is simply its vibrational state within a harmonic trap. The authors show that the finite size of the environment entails additional energy input, but do manage to switch the bit accurately and on very short timescales.

Similarities and Differences Between Nonequilibrium Steady States and Time-Periodic Driving in Diffusive Systems
https://arxiv.org/abs/1807.04104

There are two ways for a physical system to be maintained in an out of equilibrium state. Either the system is coupled to multiple baths so the transitions between states do not obey detailed balance (NESS) or there is some periodic change in the parameters (SP). This paper shows that for a continuous 1D system described by an overdamped Fokker-Planck equation for any choice of probability distribution over states and time averaged current the SP version has a higher entropy production than the NESS version.

Construction of integrated gene logic-chip
https://www.nature.com/articles/s41565-018-0202-3
In this paper, the authors integrated an RNA polymerase and corresponding DNA template in one DNA origami object, at a fixed separation. They were able to build a logic-chip by changing the geometry of the tether by which the polymerase is attached to the origami with binding of additional DNA strands, which either facilitating or inhibit access of the polymerase to the template.

Complex silica composite nanomaterials templated with DNA origami
https://www.nature.com/articles/s41586-018-0332-7
The authors employ the Stober silanization method for the production of silica-covered DNA origami structures. The resultant structures have higher resistance to adverse conditions, can keep their shape with weaker ionic strength in solution, and its Young Modulus is increased by 10.
During the experiments, different structures were silanized by this method, probing that it can be applied to the whole range of DNA origami structures while conserving their original dimensions.


Creating metamaterial building blocks with directed photochemical metallization of silver onto DNA origami templates
http://iopscience.iop.org/article/10.1088/1361-6528/aacb16
There exists limitations for the production of small optical metamaterials nanostructures with a defined structure. In this paper, the authors propose the use of DNA origami structures as canvas for the formation of silver nanostructures. Via a photochemical reaction, diammine silver can interact with the DNA backbone, covering the whole structure with silver ions. The produced structures, while respecting the geometry of the origami, grow to a self limited value, producing a continuous and uniform metal layer over the DNA.

Scalling-up molecular pattern recognition wity DNA-based winner-take-all neural networks.
https://www.nature.com/articles/s41586-018-0289-6
This present work is an improvement from previous work in which the authors improve implement neural networks using a winner-take-all computation instead of a Hopfield neural network. This new approach results in a greater versatility allowing the authors to code a pattern recognition neural network in which each bit of the pattern is coded by a DNA strand that triggers a seesaw gate releasing an intermediate (Weight multiplication). All the different intermediate products have a common domain that triggers the summation gate. After all the weights are summed, the weighted sum strand triggers another seesaw gate (annihilation gate) giving 2 waste molecules. The annihilator is designed in such a way that it only  releases the post annihilation signal if the concentration of the weighted output is higher that a certain value. This output then goes to a restoration gate (a fuel-consuming catalytic cycle) that amplifies the signal giving an output that triggers a reporter. It must be noted that not all the bits of the encoded patterns must be trigger in order to have a positive signal


16/7/2018

A synthetic enzyme built from DNA flips 10^7 lipids per second in biological membranes
https://www.nature.com/articles/s41467-018-04821-5
The authors demonstrate a DNA nanostructure that catalyses lipid flipping across lipid bilayer. Speed is 10^7 molecules / second. The results are confirmed with MD simulation and fluorescence experiment on synthetic and cell membrane.

Non-dissociative structural transitions of the Watson-Crick and reverse Watson-Crick А·Т DNA base pairs into the Hoogsteen and reverse Hoogsteen forms

https://www.nature.com/articles/s41598-018-28636-y
This paper introduce a theoretical mechanism of transition between Watson-Crick and Hoogsteen base pairs. The intermediates of the reaction for an AT base pairs are wobbly forms where the anisotropic rotation occurs without breaking hydrogen bonds.

A minimal "push-pull" bistability model explains oscillations between quiescent and proliferative cell states.
When in limited supply of glucose, S.cerevisiae populations are divided into quiescent (non-replicative) and proliferative (replicative) sub-populations. The appearance of proliferative cells is oscillatory and has a period of 3-5 hours. The switch of individual cells between subpopulations can be modelled with a simple push-pull model were quiescent cells pull other cells to remain in that state, and the proliferative pushes others to switch to quiescent. This oscillatory behaviour of the pull-push network can appear in three ways: i) diffusion of a resource produced by quiescent cells, ii) accumulation of a non-consumable, external resource or iii) production and internal consumption of a resource. In yeast metabolic network, this resource is more likely to be acetyl-coA or NADPH.

A thermodynamically consistent model of finite state machines
The authors present a description of a general finite state machine (a non-universal, but powerful, computing primitive)  that can be analysed thermodynamically. They then perform this analysis, and draw conclusions that relate efficiency to design. The framework seems promising but we are not sure about the accuracy of the analysis at this point. 


11/6/2018

The validity and breakdown of the overdamped approximation in stochastic thermodynamics: Theory and experiment
https://arxiv.org/abs/1805.09080
In this paper the authors show that the extended Kramers equation (the Fokker-Planck equation for the position, velocity and stochastic work of a Brownian particle subjected to a force) converges to the extended Smoluchowski equation (the Fokker-Planck equation for the position and stochastic work of an overdamped Brownian particle subjected to a force)  in the high damping coefficient limit. They require the friction and temperature to be uniform in space. They also experimentally verify their results.


Semantic information, agency, and nonequilibrium statistical physics
If we consider an agent that measures and interacts with its environment one way to measure the 
information the agent has about its environment is the mutual information between the state of the 
agent and the state of the environment this is called ‘syntactic information’. This paper defines ‘semantic information’ as the syntactic information that is needed to maintain the agent’s ‘viability’ at a later time.

21/5/2018
Exploring the speed limit of toehold exchange with a cartwheeling DNA acrobat
https://www.nature.com/articles/s41565-018-0130-2?WT.feed_name=subjects_dna-nanomachines
A new type of DNA walker to test the speed limit of strand-displacement-based walking speed.Core region of 13nt, toehold region of 6nt gives fastest walking speed. They tried different toehold lengths.
Force-dependent diffusion coefficient of molecular Brownian ratchets
https://arxiv.org/abs/1805.05242v1
Polymers can be pulled through pores in cell membranes by the binding of chaperone molecules that prevent the polymer from moving backwards. This is a kind of Brownian ratchet. In this paper the authors study the mean velocity and diffusion constant in stochastic models of this process. They also examine the thermodynamic efficiency of the process and connections with the thermodynamic uncertainty relation.

Molecular Computing for Markov Chains 
In the present work the authors summarize previous work on proposed biomolecular architectures for the calculation of Discrete-Time Markov chains, as well as presenting new architectures with their corresponding simulations. In these new architectures each of the species codes a possible state of the system and reaction rates code for the probabilities of the system of transitioning to a certain state. The authors distinguish inside their purposed architectures for Markovian processes between those for first order chains (based in unimolecular reactions) and those for second order chains (for processes with memory in which the evolution depends on the current state of the system)  in which the basic reaction motif is bimolecular.

An environmentally-responsive reciprocal replicating network 
https://pubs.acs.org/doi/10.1021/jacs.7b13576
In this paper, a network of two cross-catalytic chemical reactions has been designed. The reactions consist in the dimerisation of two non-biological organic molecules. The building blocks A, B, C and D dimerise, forming AB and CD. AB and CD can catalyse the formation of each other by specific interactions between their functional groups. This is the first time these kind of reciprocal reactions network are obtained without employing biological molecules.

Thermodynamic Properties of Molecular Communication 
The authors consider a model of message generation in which a message corresponds to a series of molecules of one type or another. Messages are generated by selecting molecules from two reservoirs at different concentrations; the molecule received therefore gives (some) indication of the message (sequence of boxes chosen). The authors compare the information transmitted to the work done in setting up the reservoirs.


30/4/2018
A reaction network scheme which implements the EM algorithm
This paper shows how to construct a chemical reaction network to estimate the maximum likelihood parameters of an exponential family distribution given a linear projection of some data. The network implements a generalised expectation-maximisation algorithm. One sub-network computes an M-projection and the remaining reactions compute an E-projection.

Copying of Mixed-Sequence RNA Templates inside Model  Protocells
https://pubs.acs.org/doi/10.1021/jacs.8b00639
The authors achieve non-enzymatic templated-polymerisation of RNA molecules inside lipid vesicles.
The templated-polymerisation technique consists in the binding to the a RNA template of a 3-4 nucleotides RNA primer and some free ribonucleotides, all of them activated with a phosphoroimidazolide group. They catalyze the polymerisation reaction with citrate-chelated Mg2+, which also enhances the permeability of the vesicles to primers and monomers, but not of the polymerisation products. This way they demonstrate a possible mechanism for non-enzymatic Darwinian replication inside protocells

Spontaneous emergence of self-replication in chemical reaction systems 
The authors consider a theoretical system of molecules labelled 1,2,3..., where chemical reactions i+j<->k are physically possible by conservation of mass if i+j=k (think molecule n as a chain of length n). They consider some assembly reactions as fast, and others vanishingly slow, and assign reverse disassembly rates in a thermodynamically consistent way. They observe that auto-catalytic ("self-replicating") cycles appear quite easily in such systems, and that autocatalytic cycles involving the larger molecules can become dominant after their key ingredients have been created by simpler cycles. They relate this feature to the emergence of chemical complexity. 

Synthesising life
https://www.nature.com/articles/35053176
Self-replicating RNA machines requires two machines to be in proximity; one to be the template, one to the copying machine. At low concentrations some kind of physical compartmentalisation is necessary. At high concentrations compartmentalisation is still necessary in order to provide selective pressure towards faster replicators. This is because if better self-replicators come into contact with (and thus replicate) lots of less good replicators, then the evolutionary advantage is lost. Compartmentalisation encourages self copying and promotes the evolutionary advantages.

Robust self replication of combinatorial information via crystal growth and scission
http://www.pnas.org/content/109/17/6405
In this paper the authors form DNA tile crystals which propagate information through crystallisation, where each new layer uses the previous layer as a template. A laminar flow parallel to each layer is then used to fracture the crystals, exposing new growth fronts which then propagate information. In this way the rate of information propagation is increased. The process of fracturing does not appear to reduce the accuracy of the information propogated, while occassional "monsters" are created, they do not propogate. Most errors come from the seeding process or from the accidental creation of new incorrect template polymers.

A bio-hybrid DNA rotor–stator nanoengine that moves along predefined tracks
A paper using two interlocked DNA rings, one with a T7 promoter and one with a Zinc finger motif on it. RNA transcribed from one DNA ring guides the interlocked ring structure to the next binding site where it performs a strand displacement reaction to have a stable binding. As the structure keeps transcribing the RNA, the ring structure can move on to the next binding site.


12/3/2018
Multidimensional biochemical information processing of dynamical patterns
Cells can transfer messages using the dynamical concentration of messaging molecules. In this paper the author discusses a model where the signal a linear combination of basis functions and it is decoded using linear decoders with independent input noise and no intrinsic noise. They find that when the noise is low it is optimal for the decoders to use different responses functions whereas when the noise is high it is optimal to repeat identical response functions.


A proof of the Global Attractor Conjecture in the single linkage class
The paper essentially presents a proof of the Global Attractor Conjecture, when the underlying reaction network has only one connected component (or linkage class). It uses the idea of partitioning vectors along a sequence of trajectory points into chunks which are commensurate to construct a family of Lyapunov functions that decrease along a trajectory. These Lyapunov functions explode when they reach the boundary, implying that the equilibrium point is a global attractor.

Programmable autonomous synthesis of single-stranded DNA 
This paper is an explanation and concept demonstration of a new approach for building DNA reaction network circuits called the "primer exchange reaction" (PER). The basic idea is that a short primer can be repeatedly extended in a programmed way by transitory binding to specific toeholds of DNA hairpins. During these short periods of bonding, the primer is extended by a polymerase, using the DNA sequence of the hairpin stem as a template. The result is an extended primer with a new domain at the leading edge, which can then bind to another hairpin. This approach allows the programmable synthesis of a given DNA sequence and is proved to be a versatile applications since it can create reaction cascades that can be tinkered to multiple applications such as in situ synthesis of the staples of a DNA origami, creating a DNAzyme able to degrade a given RNA sequence using as an input a different siRNA or code boolean logic gates to cite a few of the circuits devised in the paper.

A coarse-grained model for DNA origami
https://www.ncbi.nlm.nih.gov/pubmed/29267876
The paper introduces a new online tool to quickly simulate and analyze the conformation of DNA origami structures. The tool is used to predict the final structure and the dynamics of some already published DNA origami designs, resulting in reliable coarse-grained simulations. The simulation results were validated by using AFM, for structure; FRET, for dynamics; and all-atom simulations. The tool is publicly available and can be used by simply uploading the CadNano file of the DNA origami structure to https://vsb.fbb.msu.ru/cosm/. 

Proof of concept continuous event logging in living cells
The idea is somewhat similar to a recent Science paper (http://science.sciencemag.org/content/early/2017/11/20/science.aao0958): to incorporate sequences of DNA into the genome in a consecutive manner. If incorporation of certain sequences can be triggered by specific signals, then the mechanism could be used to log events over time. The mechanism is based on an "integrase" enzyme that acts at a specific recognition site, inserting one of several sequences that each contain a new copy of the recognition site (so that subsequent additions can occur). The system isn't fully functional yet, but they test several key parts. 


12/2/2018
Performance limits and trade-offs in entropy-driven biochemical computers
or
In this paper the author defines ‘entropy driven computation’ as a chemical reaction network modelled as a continuous time Markov chain relaxing to its equilibrium distribution. They consider systems where the linear noise approximation is valid. They show that there is a trade-off between the accuracy of the computation and the entropy production. They also show that when you consider the fact that you have to measure the result of the computation there is a trade off between the entropy production and time, and accuracy and time.

Heterochiral DNA Strand-Displacement Circuits.
This work exploits the presence of chirality in nucleic acids, showing how to make circuits with different nucleic acids (D-DNA, L-DNA, D-RNA and PNA). The authors displayed the potential to work in parallel with the same inputs and controlled crosstalk and improved resilence to environmental RNA noise, expanding the functionalities of the strand displacement circuits.

Poster: Folding/Unfolding Thermodynamics of Three-Way and Four-Way Junctions
http://www.cell.com/biophysj/fulltext/S0006-3495(17)31745-9                                    
This poster continues previous work (see below) that discusses the thermodynamic parameters of Three-Way Junctions (TWJ) and Four-Way Junctions (FWJ) in a DNA complex. For TWJ the authors determine that the junctions unfold biphasically at low salt concentration (10 mM sodium phosphate buffer) and triphasically at high salt concentration (10 mM sodium phosphate buffer + 0.2 M NaCl) (ΔH= 118~119 kcal/mol; ΔG=12.6~17.5 kcal/mol respectively). The difference is produced because at high salt concentration, the unfolding of the two strands is sequential and not simultaneous. On the other hand, FWJ unfolds biphasically at low and high salt concentrations (ΔH= 135~149 kcal/mol; ΔG=17.5~24.9 kcal/mol respectively). The existence of only two steps during the unfolding suggest a high cooperativity.  Single Value Decomposition analysis also suggest that FWJ have two possible folded conformations at low salt, but only one at high salt, that will likely correspond with the anti-parallel stacked X structure.

Full paper: Melting Behavior of a DNA Four-Way Junction Using Spectroscopic and Calorimetric Techniques
https://pubs.acs.org/doi/10.1021/jacs.7b06429

A short note on the Lyapunov function for complex-balanced chemical reaction networks
This short note gives a crisp proof of the fact that free energy Helmholtz function is a true Lyapunov function for chemical reaction networks. This is the proof given by Horn and Jackson[1974], with the removal of the notion of “complex space”.




24/1/2018
Hierarchical control of enzymatic actuators using DNA-based switchable memories
https://www.nature.com/articles/s41467-017-01127-w?WT.feed_name=subjects_synthetic-biology
The authors demonstrate a mechanism for coupling nucleic acid/enzyme circuits in a pre-existing paradigm to the production of large DNA strands that can regulate protein function. They focus on the question of how coupling the downstream output to the system changes its behaviour, a phenomenon known as retroactivity.


Information Integration and Energy Expenditure in Gene Regulation
The paper studies the notion of information integration and energy consumption in the context of “sharpness of gene expression”. The define sharpness of a gene as the amount of gene expressed as a function of the concentration of the transcription factor. At thermodynamic equilibrium with n binding sites and higher order cooperatives, there is a “Hopfield barrier” to sharpness given by the Hill function of coefficient n. By expending energy, one can shift the system out of equilibrium and this Hopfield barrier can be breached.

Effective thermodynamics for a marginal observer
The Crooks fluctuation relation relates the ratio of the probability of a forward trajectory of a stochastic system to the probability of the backwards trajectory to the entropy production in the environment in that trajectory. Calculating the entropy production requires knowledge of transitions between all of the states of the system. This paper shows that if you can only observe a subset of the states a modified fluctuation relation still holds.

A self-assembled nanoscale robotic arm controlled by electric fields http://science.sciencemag.org/content/359/6373/296
This work features the description of DNA nanomachine consisting of an arm attached to a DNA origami platform capable of rotating, following the direction of an electric field. This design has proved to be able to displace cargoes in a directed manner while reducing the effect of thermal diffusion and augmenting the performance speed by 5 orders of magnitude when compared to similar designs based on chemical fuel consumption.

Non-equilibrium effect in the allosteric regulation of the bacterial flagellar switch, and
The nonequilibrium mechanism for ultrasensitivity in a biological switch: Sensing by Maxwell's demons
The first paper provides the background for the second paper. Both discuss the switching of motors which drive bacterial flagella from clockwise to counterclockwise modes and vice versa. Due to the structure of the flagella, when the motors rotate counter clockwise, all the flagella wrap around each other and form a long tail, allowing straight line motion or runs. When they rotate clockwise they unwrap and the bacterium tumbles. The first paper discusses experimentally finding non-equilibrium effects in the switching mechanism due to motor torque. The second paper attempts to analyse this mathematically using familiar stochastic techniques.

18/1/2018
Local equilibrium in bird flocks
In this paper, a new method of dynamical inference is developed to compensate for slow sampling rates. This allows analysis of both local interactions and network rearrangement in the regime where network rearrangement times are slow with respect to local relaxation time; a fact which is demonstrated to be true for starling murmurations. Thus bird flocks can be considered to be in a state of local equilibrium, with the system quickly responding to slow changes in network.


Stochastic Thermodynamic Interpretation of Information Geometry
In this paper the author uses information geometric quantities to derive bounds in stochastic thermodynamics including a thermodynamic uncertainty relation.

Thermodynamically Consistent Coarse Graining of Biocatalysts beyond Michaelis--Menten
https://arxiv.org/abs/1709.06045
Many catalysts may couple to a range of cofactors and have a number of substrates/products. Is it possible to systematically coarse-grain the system, getting rid of individual transitions and instead simply have a small number of effective reactions (preferably one), each associated with an overall net current, in a way that preserves both the turnover of substrates/products AND the entropy generation? 

6/11/2017
Computing properties of stable configurations of thermodynamic binding networks
This paper describes a method to calculate all the possible thermodynmaic tradeoffs (focused in enthalpy and entropy) in DNA chemical reaction networks allowing the prediction of all the possible pairings given at a domain level, which can result on the prediction and estimation of the rates of undesired leak reaction rates. Although very useful in principle, this work is only a first limited step since it only predicts and calculates at the abstracted domain level.

Cell cycle switch computes approximate majority
https://www.nature.com/articles/srep00656
The paper shows that a biologically plausible circuit, namely a cell-cycle switch, simulates the approximate majority algorithm. Deterministic (ODEs), stochastic (gillespie simulations) and probabilistic analyses are performed to compare the performance of the two circuits. Though the performance of the cycle-cycle switch is slightly sub-optimal compared to the circuit computing the approximate majority algorithm, the introduction of a feedback loop called the "greatwall kinase" corrects this effect, by improving both the speed and conversion to majority.

Synchrony and pattern formation of coupled genetic oscillators on a chip of artificial cells
In the paper, the authors produce a silicon microfluidics-chip with several compartments interconnected by a central channel. Each of these compartments are functionalized with several DNA sequences that encodes proteins for an oscillatory network and a reporter (GFP). The oscillatory behaviour is produced by flowing through the central channel an E.coli transcription-extract with a transcription activator and repressor that reach through diffusion to the functionalized compartments.

By altering the ratio of the different genes' promoters, the researchers are able to change the oscillation frequency of the cells. In addition, the connection of the compartments between them with the central channel produce a synchronization mediated only by diffusion. While the cells produce random oscillations without communication between them, when communicated they acquire the same frequency, determined by the slowest one.  This synchronization strength is easily controlled by varying the geometry or breaking the symmetry of the flow.

This microfluidic approach is a useful bottom-up approach for genetic-oscillator interactions, which allows to precisely control the experimental parameters and observe a wide variety of oscillatory behaviours.

Mapping of uncertainty relations between continuous and discrete time
This paper shows a relationship between the thermodynamic uncertainty relation for discrete and continuous time Markov chains in the long time limit. The variance of a current is always greater in the continuous time case because of the uncertainty in the time of the transitions. They use this relationship to transform a bound called the Proesmans-Van den Broeck bound for discrete time process to one for continuous time processes and show that is tighter than the Barato-Gingrich bound.

Modular probes for enriching and detecting complex nucleic acid sequences
The authors introduce a design for a DNA "probe" intended to detect the presence of complementary sequences in solution. This particular design is modular, allowing the authors to build longer probes than were previously possible, and includes small subsections in which the probe is not specific to a particular target sequence (at the joins between modules). This could be viewed as an advantage or a disadvantage, depending on context. 


30/10/2017
Mixed analytical-stochastic simulation method for the recovery of a Brownian gradient source from probability fluxes to small windows
In this paper the authors show how a cell can detect the position of a source of Brownian particles using the particle flux into absorbing patches on its surface. They also demonstrate a simulation method that uses Green’s functions for efficient simulation of diffusion in some regions and explicit integration of Brownian motion via Euler’s method in others.

Robust Weak Chimeras in Oscillator Networks with Delayed Linear
and Quadratic Interactions

Chimera states are complex spatio-temporal patterns in which domains of synchronous and asynchronous dynamics coexist in coupled systems of oscillators. In this paper, the authors show the production of robust chimeras in networks of two populations of two oscillators. They obtain this with a weak coupling function with two sinusoidal terms: a linear and quadratic time-delayed interactions.



They test the approach numerically with the Brusselator model and experimentally with an electrochemical  oscillatory reaction. The results show how complex collective dynamics in phase models translate into limit cycle oscillator networks in real biological processes.



Maximal aggregation of polynomial dynamical systems
The paper give an algorithm for the reduction of ordinary differential equations up to an equivalence relation over it’s variables. The algorithm preserves structure and variables of interest. Applications of this algorithm are presented in the context of regulatory networks, evolutionary game theory and molecular biology.

Post CMOS Computing Beyond Si: DNA Computing as Future Alternative. (http://ieeexplore.ieee.org/document/7829537/)
This paper is a brief review of the DNA computing field in which the different algorithmic operations that can be performed with DNA are described. The original approaches in the field (the Adelman-Lipton model and the stickers model) are also described in detail. This work also offers a very brief summary of the kind of problems that have been tackled, as well as their problems in implementing arithmetic operations. Worthy as a basis for introducing students to the field

Constructor Theory of Thermodynamics
Oxford-based researchers are endeavouring to re-frame fundamental ideas of physics in terms of whether it is theoretically possible to build devices (or "constructors") that can be guaranteed to achieve a certain "task". This paper seeks to do this for the laws of thermodynamics. In particular, much of the effort is spent trying to develop a rigorous and  general definition of work and heat.


16/10/2017
Sufficient physical conditions for self-replication
https://arxiv.org/pdf/1709.09191.pdf
The authors introduce a simple model that can exhibit auto-catalytic cycles that eventually lead to exponential growth of finite-size clusters from a pool of monomers (for this it is crucial that the maximum cluster size is capped). They observe that this exponential growth is favoured when autocatalytic cycles involve reactions that are highly specific - ie., components involved in the cycle overwhelmingly undergo reactions in the cycle, rather than competing alternative reactions.

A tensegrity driven DNA nanopore.
This paper describes the design of a DNA nanopore the mimics the function of those at biological membrane.  It consists in 6 B-DNA helixes forming the main structure of the pore, which is modified with hydrophobic domains that allow its insertion in lipid bilayers and block the pore lumen when closed.  The opening mechanism of the pore involves a ssDNA sequence on the top of the pore that in presence of its complementary strand forms a stiff double helix that with its tension forces changes in the structure of the pore and consequently its opening.

Conservation Laws shape Dissipation
In this paper the authors describe a general formulation of stochastic thermodynamics with multiple reservoirs. They show how conserved quantities cause the forces from the reservoirs to be absorbed into the potentials of the states of the system in the local detailed balance equation. They also show how to separate the entropy production into a part that depends on how the potentials are changed over time, a part that depends on the difference between the potential of the initial and final state and a part that depends on the fundamental forces.

Iterated function systems for DNA replication
Here, Gaspard generalises his previous solutions for solving the mechanics of the creation of polymer copies by no longer allowing the simplification that all matches can be considered "correct" or "incorrect". Instead, for DNA, he considers the dynamics of all 16 possible base pair combinations. This extra heterogeneity leads to imbalances in concentration between nucleotides at different points in the chain.  This, in turn, leads to regions of "anomalous drift" where the growth of the polymer is sub linear.

Exponential growth and selection in self-replicating materials from DNA origami rafts
The authors have successfully created a system in which DNA origami rafts form dimers that co-operatively catalyse their own formation in a specific manner,  leading to exponential growth of specific dimer pairs. This process involves a complex external protocol involving cycling of temperatures and periodic UV exposure.

Thermodynamically Consistent Coarse Graining of Biocatalysts
The paper provides a mechanism to understand properties of the reaction network at the coarse grained level. In particular, physical quantities like flux, reaction stoichiometry and force relations are provided at the coarse-grained level of the reaction network. The entire mechanism is ensured to be thermodynamically consistent. Examples are illustrated using a single catalyst that reacts with two substrates to form a product, and a representative model of active membrane protein transport.


25/09/2017
A cargo-shorting DNA robot.
The most recent work from the Winfree and Qian groups describes the construction of a modular DNA walker capable of carrying  DNA cargoes. Through a random walk process the aforementioned cargoes are selectively transported to a specific zone of a DNA origami.

Associative Pattern Recognition Through Macro-molecular Self-Assembly
Multifarious assembly mixtures: Systems allowing  retrieval of diverse stored structures
The authors ask how many separate self-assembly targets can be programmed into the interactions between a mixture of monomers, assuming that monomers must be re-used (in different patterns) in each fully-assembled structure. They explore the conditions under which a single well-formed assembly can be triggered by seeding a small part of it, and then relate this process to the idea of retrieving memories. 


11/09/2017
This paper considers chemical reaction networks forced out of equilibrium by a generalised chemical driving force (which is justified by appealing to implicit degrees of freedom). They watch the system evolve with time and observe a bi-modal distribution of outcomes in which, while most of the possible networks are in equilibrium or lowly dissipative, a small fraction of the configurations evolves to become much more highly dissipative and finely tuned to the work source of the environment than the rest. These finely-tuned setups occur much more often than would be expected by chance. 

This paper analysis a system which involves polymer creation through processes of random ligation and auto-catalysis. It finds that, in a regime dominated by auto-catalysis, repetitive, highly patterned structures are by far the most common. It suggests two possible explanations, one short term and far from equilibrium, and one in the steady state. Both explanations hinge on the idea that longer polymers can absorb more different kinds of material when creating themselves through auto-catalysis, and for a given amount of input material, and regular polymers can form longer chains than irregular ones when creating themselves by random ligation.

Marzen and Crutchfield present a theoretical treatment of conditionally Markovian systems Y driven by hidden-Markovian environments X. They are able to derive expressions for certain  information-theoretic and thermodynamic quantities related to the combined process. They use these expressions to study information and dissipation in the sensing of ligands that bind cooperatively to a sensor.  


The paper gives a sufficient condition for a chemical reaction network to have an extinction event. More explicitly, they introduce the notion of a dominated expanded reaction network and provide a set of conditions on this network that do not need to be satisfied for an extinction event to occur. Solving such a system of equalities/inequalities makes the question of finding an extinction event in the reaction network amenable to algorithmic approaches.


07/08/2017
Markov chain models of stochastic processes without detailed balance implicitly contain external degrees of freedom that drive the system. This paper shows how to embed the Markov chain in a larger Markov chain that explicitly includes these degrees of freedom. This larger Markov chain allows detailed balance (it satisfies Kolmogorov’s criterion) but is out of equilibrium and the embedding is only accurate for short times compared to the relaxation time of the driving degrees of freedom.

In this paper, the authors demonstrate the ability to correlate the number of photons in an optical cavity with the state of a qbit, based on the fact that the interactions between the cavity change the energy gap of the qbit/resonant frequency of the cavity. This correlation allows for an excess of stimulated emission over absorption when the qbit is exposed to light at the natural frequency f the isolated qbit.


24/07/2017
A first major step towards a systematic predictor for DNA hybridisation rates. Based on a wealth of data, the authors use a combination of metrics that can be easily calculated from the sequences to predict hybridisation rates. The approach is largely phenomenological, and currently only applies to one strand length, but its a big step forward non the less. 

In this paper, the authors discuss fluctuations in the ‘information flow’, which is part of the time derivative of the mutual information between two interacting stochastic systems. They show that when considering just one of the two coupled systems, the information flow must be added to the entropy production for a fluctuation theorem to hold. They apply this to a system of two interacting Brownian particles.
The paper makes a connection between stochastic and deterministic chemical reaction networks. In particular, it shows that for complex balanced networks, the Lyapunov function of the deterministic reaction network arises as a scaling limit of the non-equilibrium potential corresponding to the stationary distribution of it’s stochastic network. In addition, it extends this result to some birth-death processes which are not complex balanced, however does not prove results in a greater generality.

This paper sets up a simple system that trains a neural network the form of a rule for generating outputs. It takes an input drawn randomly from a set potential, and acts on it with a teacher rule and a student rule, giving two different outcomes. The two outputs are compared and the student rule is updated to give an output closer to the output given by the teacher rule. This paper states that the increase in mutual information between the teacher and student rules must be less than the free energy dissipated for the process of the student learning from the teacher. 

This paper features the description of the development of an aptamer-based platform for the Influenza virus diagnosis. The aptamers obtained through artificial evolution in this work are characterized by their capability of binding to many influenza virus subtypes, making it more robust to variations on the virus due to mutations and recombination.


03/07/2017
The authors find a bound on the distribution of the infimum of entropy production in a trajectory of a stochastic process. This can be used to find a bound on the average maximum backwards detour of a molecular motor. They calculate other quantities such as the probability of a trajectory reaching a positive entropy production before reaching the same magnitude negative entropy production and the ratio of the probability distribution of the time to reach those two states.


The RNA world hypothesis suggests that early life used RNA as both an information carrier and as chemically active catalysts. In particular, an RNA-based RNAp could in principle allow for RNA-based copying of RNA. Whilst some RNA-based polymerases do exist in nature, they are not effective at polymerising long, arbitrary sequences. Here, the authors obtain an RNA-based RNAp that can do just that by several rounds of selective evolution. Note that the functioning of the RNAp is restricted to growing a copy sequence on a single-stranded template; persistent copies can only be produced by thermal cycling.

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