Spin-Echo Silencing Using a Current-Biased Frequency-Tunable Resonator.

The ability to control microwave emission from a spin ensemble is a requirement of several quantum memory protocols. Here, we demonstrate such ability by using a resonator whose frequency can be rapidly tuned with a bias current. We store excitations in an ensemble of rare-earth ions and suppress on demand the echo emission ("echo silencing") by two methods: (1) detuning the resonator during the spin rephasing, and (2) subjecting spins to magnetic field gradients generated by the bias current itself. We also show that spin coherence is preserved during silencing.

Emphysematous gastritis in a newborn: Is it very rare or do we just miss it?

Emphysematous gastritis is a rare and life-threatening condition caused by gastric inflammation and intramural gas formation, most often diagnosed through radiological evidence of a radiolucent shadow in the stomach wall in the clinical scenario of severe sickness. We report a case of emphysematous gastritis secondary to early-onset neonatal sepsis in a newborn which, to the best of our knowledge, has not otherwise been reported. Is it very rare or do we just miss it?

Multimode Storage of Quantum Microwave Fields in Electron Spins over 100 ms.

We report long coherence times (up to 300 ms) for near-surface bismuth donor electron spins in silicon coupled to a superconducting microresonator, biased at a clock transition. This enables us to demonstrate the partial absorption of a train of weak microwave fields in the spin ensemble, their storage for 100 ms, and their retrieval, using a Hahn-echo-like protocol. Phase coherence and quantum statistics are preserved in the storage.

Pulsed electron spin resonance spectroscopy in the Purcell regime.

In EPR, spin relaxation is typically governed by interactions with the lattice or other spins. However, it has recently been shown that given a sufficiently strong spin-resonator coupling and high resonator quality factor, the spontaneous emission of microwave photons from the spins into the resonator can become the main relaxation mechanism, as predicted by Purcell. With increasing attention on the use of microresonators for EPR to achieve high spin-number sensitivity it is important to understand how this novel regime influences measured EPR signals, for example the amplitude and temporal shape of the spin-echo. We study this regime theoretically and experimentally, using donor spins in silicon, under different conditions of spin-linewidth and coupling homogeneity. When the spin-resonator coupling is distributed inhomogeneously, we find that the effective spin-echo relaxation time measured in a saturation recovery sequence strongly depends on the parameters for the detection echo. When the spin linewidth is larger than the resonator bandwidth, the different Fourier components of the spin echo relax with different characteristic times - due to the role of the resonator in driving relaxation - which results in the temporal shape of the echo becoming dependent on the repetition time of the experiment.

An exhaustive survey of regular peptide conformations using a new metric for backbone handedness (h).

The Ramachandran plot is important to structural biology as it describes a peptide backbone in the context of its dominant degrees of freedom-the backbone dihedral angles φ and ψ (Ramachandran, Ramakrishnan & Sasisekharan, 1963). Since its introduction, the Ramachandran plot has been a crucial tool to characterize protein backbone features. However, the conformation or twist of a backbone as a function of φ and ψ has not been completely described for both cis and trans backbones. Additionally, little intuitive understanding is available about a peptide's conformation simply from knowing the φ and ψ values of a peptide (e.g., is the regular peptide defined by φ = ψ =  - 100°  left-handed or right-handed?). This report provides a new metric for backbone handedness (h) based on interpreting a peptide backbone as a helix with axial displacement d and angular displacement θ, both of which are derived from a peptide backbone's internal coordinates, especially dihedral angles φ, ψ and ω. In particular, h equals sin(θ)d∕|d|, with range [-1, 1] and negative (or positive) values indicating left(or right)-handedness. The metric h is used to characterize the handedness of every region of the Ramachandran plot for both cis (ω = 0°) and trans (ω = 180°) backbones, which provides the first exhaustive survey of twist handedness in Ramachandran (φ, ψ) space. These maps fill in the 'dead space' within the Ramachandran plot, which are regions that are not commonly accessed by structured proteins, but which may be accessible to intrinsically disordered proteins, short peptide fragments, and protein mimics such as peptoids. Finally, building on the work of (Zacharias & Knapp, 2013), this report presents a new plot based on d and θ that serves as a universal and intuitive alternative to the Ramachandran plot. The universality arises from the fact that the co-inhabitants of such a plot include every possible peptide backbone including cis and trans backbones. The intuitiveness arises from the fact that d and θ provide, at a glance, numerous aspects of the backbone including compactness, handedness, and planarity.

Prospective bacterial quorum sensing inhibitors from Indian medicinal plant extracts.

As virulence of many pathogenic bacteria is regulated by the phenomenon of quorum sensing (QS), the present study aimed to find the QS-inhibiting (QS-I) property (if any) in 61 Indian medicinal plants. The presence of QS-I compound in the leaf extract was evaluated by its ability to inhibit production of pigment in Chromobacterium violaceum MTCC 2656 (violacein) and Pseudomonas aeruginosa MTCC 2297 (pyocyanin) or swarming of P. aeruginosa MTCC 2297. Extracts of three plants, Astilbe rivularis, Fragaria nubicola and Osbeckia nepalensis, have shown a dose-dependent inhibition of violacein production with no negative effect on bacterial growth. Inhibition of pyocyanin pigment production and swarming motility in P. aeruginosa MTCC 2297 was also shown. Based on the results obtained by gas chromatography-mass spectroscopy (GC-MS) and thin-layer chromatography-direct bioautography (TLC-DB), it was concluded that triterpenes and flavonoid compounds found in the three plant extracts could have QS-I activity. SIGNIFICANCE AND IMPACT OF THE STUDY: A novel alternative prospect to prevent bacterial infections without inhibiting the growth is to apply chemicals that inhibit quorum sensing mechanism of the pathogens. Antiquorum property of 61 medicinal plants was evaluated by the ability of their leaf extract(s) to inhibit production of pigment (violacein in Chromobacterium violaceum MTCC 2656, pyocyanin in Pseudomonas aeruginosa MTCC 2297) or swarming in P. aeruginosa MTCC 2297. The most prospective plants (for the development of quorum sensing inhibitor), showing inhibition of violacein production without affecting bacterial growth, were Astilbe rivularis, Fragaria nubicola and Osbeckia nepalensis.

Structure based sequence analysis of viral and cellular protein assemblies.

It is well accepted that, in general, protein structural similarity is strongly related to the amino acid sequence identity. To analyze in great detail the correlation, distribution and variation levels of conserved residues in the protein structure, we analyzed all available high-resolution structural data of 5245 cellular complex-forming proteins and 293 spherical virus capsid proteins (VCPs). We categorized and compare them in terms of protein structural regions. In all cases, the buried core residues are the most conserved, followed by the residues at the protein-protein interfaces. The solvent-exposed surface shows greater sequence variations. Our results provide evidence that cellular monomers and VCPs could be two extremes in the quaternary structural space, with cellular dimers and oligomers in between. Moreover, based on statistical analysis, we detected a distinct group of icosahedral virus families whose capsid proteins seem to evolve much slower than the rest of the protein complexes analyzed in this work.

The Ramachandran Number: An Order Parameter for Protein Geometry.

Three-dimensional protein structures usually contain regions of local order, called secondary structure, such as α-helices and ß-sheets. Secondary structure is characterized by the local rotational state of the protein backbone, quantified by two dihedral angles called ϕ and ψ. Particular types of secondary structure can generally be described by a single (diffuse) location on a two-dimensional plot drawn in the space of the angles ϕ and ψ, called a Ramachandran plot. By contrast, a recently-discovered nanomaterial made from peptoids, structural isomers of peptides, displays a secondary-structure motif corresponding to two regions on the Ramachandran plot [Mannige et al., Nature 526, 415 (2015)]. In order to describe such 'higher-order' secondary structure in a compact way we introduce here a means of describing regions on the Ramachandran plot in terms of a single Ramachandran number, [Formula: see text], which is a structurally meaningful combination of ϕ and ψ. We show that the potential applications of [Formula: see text] are numerous: it can be used to describe the geometric content of protein structures, and can be used to draw diagrams that reveal, at a glance, the frequency of occurrence of regular secondary structures and disordered regions in large protein datasets. We propose that [Formula: see text] might be used as an order parameter for protein geometry for a wide range of applications.

Predicting the outcome of the growth of binary solids far from equilibrium.

The growth of multicomponent structures in simulations and experiments often results in kinetically trapped, nonequilibrium objects. In such cases we have no general theoretical framework for predicting the outcome of the growth process. Here we use computer simulations to study the growth of two-component structures within a simple lattice model. We show that kinetic trapping happens for many choices of growth rate and intercomponent interaction energies, and that qualitatively distinct kinds of kinetic trapping are found in different regions of parameter space. In a region in which the low-energy structure is an "antiferromagnet" or "checkerboard," we show that the grown nonequilibrium structure displays a component-type stoichiometry that is different from the equilibrium one but is insensitive to growth rate and solution conditions. This robust nonequilibrium stoichiometry can be predicted via a mapping to the jammed random tiling of dimers studied by Flory, a finding that suggests a way of making defined nonequilibrium structures in experiment.

Design, Synthesis, Assembly, and Engineering of Peptoid Nanosheets.

Two-dimensional (2D) atomically defined organic nanomaterials are an important material class with broad applications. However, few general synthetic methods exist to produce such materials in high yields and to precisely functionalize them. One strategy to form ordered 2D organic nanomaterials is through the supramolecular assembly of sequence-defined synthetic polymers. Peptoids, one such class of polymer, are designable bioinspired heteropolymers whose main-chain length and monomer sequence can be precisely controlled. We have recently discovered that individual peptoid polymers with a simple sequence of alternating hydrophobic and ionic monomers can self-assemble into highly ordered, free-floating nanosheets. A detailed understanding of their molecular structure and supramolecular assembly dynamics provides a robust platform for the discovery of new classes of nanosheets with tunable properties and novel applications. In this Account, we discuss the discovery, characterization, assembly, molecular modeling, and functionalization of peptoid nanosheets. The fundamental properties of peptoid nanosheets, their mechanism of formation, and their application as robust scaffolds for molecular recognition and as templates for the growth of inorganic minerals have been probed by an arsenal of experimental characterization techniques (e.g., scanning probe, electron, and optical microscopy, X-ray diffraction, surface-selective vibrational spectroscopy, and surface tensiometry) and computational techniques (coarse-grained and atomistic modeling). Peptoid nanosheets are supramolecular assemblies of 16-42-mer chains that form molecular bilayers. They span tens of microns in lateral dimensions and freely float in water. Their component chains are highly ordered, with chains nearly fully extended and packed parallel to one another as a result of hydrophobic and electrostatic interactions. Nanosheets form via a novel interface-catalyzed monolayer collapse mechanism. Peptoid chains first assemble into a monolayer at either an air-water or oil-water interface, on which peptoid chains extend, order, and pack into a brick-like pattern. Upon mechanical compression of the interface, the monolayer buckles into stable bilayer structures. Recent work has focused on the design of nanosheets with tunable properties and functionality. They are readily engineerable, as functional monomers can be readily incorporated onto the nanosheet surface or into the interior. For example, functional hydrophilic "loops" have been displayed on the surfaces of nanosheets. These loops can interact with specific protein targets, serving as a potentially general platform for molecular recognition. Nanosheets can also bind metal ions and serve as 2D templates for mineral growth. Through our understanding of the formation mechanism, along with predicted features ascertained from molecular modeling, we aim to further design and synthesize nanosheets as robust protein mimetics with the potential for unprecedented functionality and stability.

Landscape of kinetically trapped binary assemblies.

For two-component assemblies, an inherent structure diagram (ISD) is the relationship between set inter-subunit energies and the types of kinetic traps (inherent structures) one may obtain from those energies. It has recently been shown that two-component ISDs are apportioned into regions or plateaux within which inherent structures display uniform features (e.g., stoichometries and morphologies). Interestingly, structures from one of the plateaux were also found to be robust outcomes of one type of non-equilibrium growth, which indicates the usefulness of the two-component ISD in predicting outcomes of some types of far-from-equilibrium growth. However, little is known as to how the ISD is apportioned into distinct plateaux. Also, while each plateau displays classes of structures that are morphologically distinct, little is known about the source of these distinct morphologies. This article outlines an analytic treatment of the two-component ISD and shows that the manner in which any ISD is apportioned arises from a single unitless order parameter. Additionally, the analytical framework allows for the characterization of local properties of the trapped structures within each ISD plateau. This work may prove to be useful in the design of novel classes of robust nonequilibrium assemblies.

Modeling sequence-specific polymers using anisotropic coarse-grained sites allows quantitative comparison with experiment.

Certain sequences of peptoid polymers (synthetic analogs of peptides) assemble into bilayer nanosheets via a nonequilibrium assembly pathway of adsorption, compression, and collapse at an air-water interface. As with other large-scale dynamic processes in biology and materials science, understanding the details of this supramolecular assembly process requires a modeling approach that captures behavior on a wide range of length and time scales, from those on which individual side chains fluctuate to those on which assemblies of polymers evolve. Here, we demonstrate that a new coarse-grained modeling approach is accurate and computationally efficient enough to do so. Our approach uses only a minimal number of coarse-grained sites but retains independently fluctuating orientational degrees of freedom for each site. These orientational degrees of freedom allow us to accurately parametrize both bonded and nonbonded interactions and to generate all-atom configurations with sufficient accuracy to perform atomic scattering calculations and to interface with all-atom simulations. We have used this approach to reproduce all available experimental X-ray scattering data (for stacked nanosheets and for peptoids adsorbed at air-water interfaces and in solution), in order to resolve the microscopic, real-space structures responsible for these Fourier-space features. By interfacing with all-atom simulations, we have also laid the foundation for future multiscale simulations of sequence-specific polymers that communicate in both directions across scales.

Peptoid nanosheets exhibit a new secondary-structure motif.

A promising route to the synthesis of protein-mimetic materials that are capable of complex functions, such as molecular recognition and catalysis, is provided by sequence-defined peptoid polymers--structural relatives of biologically occurring polypeptides. Peptoids, which are relatively non-toxic and resistant to degradation, can fold into defined structures through a combination of sequence-dependent interactions. However, the range of possible structures that are accessible to peptoids and other biological mimetics is unknown, and our ability to design protein-like architectures from these polymer classes is limited. Here we use molecular-dynamics simulations, together with scattering and microscopy data, to determine the atomic-resolution structure of the recently discovered peptoid nanosheet, an ordered supramolecular assembly that extends macroscopically in only two dimensions. Our simulations show that nanosheets are structurally and dynamically heterogeneous, can be formed only from peptoids of certain lengths, and are potentially porous to water and ions. Moreover, their formation is enabled by the peptoids' adoption of a secondary structure that is not seen in the natural world. This structure, a zigzag pattern that we call a Σ('sigma')-strand, results from the ability of adjacent backbone monomers to adopt opposed rotational states, thereby allowing the backbone to remain linear and untwisted. Linear backbones tiled in a brick-like way form an extended two-dimensional nanostructure, the Σ-sheet. The binary rotational-state motif of the Σ-strand is not seen in regular protein structures, which are usually built from one type of rotational state. We also show that the concept of building regular structures from multiple rotational states can be generalized beyond the peptoid nanosheet system.

Clean carbon nanotubes coupled to superconducting impedance-matching circuits.

Coupling carbon nanotube devices to microwave circuits offers a significant increase in bandwidth (BW) and signal-to-noise ratio. These facilitate fast non-invasive readouts important for quantum information processing, shot noise and correlation measurements. However, creation of a device that unites a low-disorder nanotube with a low-loss microwave resonator has so far remained a challenge, due to fabrication incompatibility of one with the other. Employing a mechanical transfer method, we successfully couple a nanotube to a gigahertz superconducting matching circuit and thereby retain pristine transport characteristics such as the control over formation of, and coupling strengths between, the quantum dots. Resonance response to changes in conductance and susceptance further enables quantitative parameter extraction. The achieved near matching is a step forward promising high-BW noise correlation measurements on high impedance devices such as quantum dot circuits.

Heterogeneity of functional groups in a metal-organic framework displays magic number ratios.

Multiple organic functionalities can now be apportioned into nanoscale domains within a metal-coordinated framework, posing the following question: how do we control the resulting combination of "heterogeneity and order"? Here, we report the creation of a metal-organic framework, MOF-2000, whose two component types are incorporated in a 2:1 ratio, even when the ratio of component types in the starting solution is varied by an order of magnitude. Statistical mechanical modeling suggests that this robust 2:1 ratio has a nonequilibrium origin, resulting from kinetic trapping of component types during framework growth. Our simulations show how other "magic number" ratios of components can be obtained by modulating the topology of a framework and the noncovalent interactions between component types, a finding that may aid the rational design of functional multicomponent materials.

Growth of equilibrium structures built from a large number of distinct component types.

We use simple analytic arguments and lattice-based computer simulations to study the growth of structures made from a large number of distinct component types. Components possess 'designed' interactions, chosen to stabilize an equilibrium target structure in which each component type has a defined spatial position, as well as 'undesigned' interactions that allow components to bind in a compositionally-disordered way. We find that high-fidelity growth of the equilibrium target structure can happen in the presence of substantial attractive undesigned interactions, as long as the energy scale of the set of designed interactions is chosen appropriately. This observation may help explain why equilibrium DNA 'brick' structures self-assemble even if undesigned interactions are not suppressed [Ke et al. Science, 338, 1177, (2012)]. We also find that high-fidelity growth of the target structure is most probable when designed interactions are drawn from a distribution that is as narrow as possible. We use this result to suggest how to choose complementary DNA sequences in order to maximize the fidelity of multicomponent self-assembly mediated by DNA. We also comment on the prospect of growing macroscopic structures in this manner.

Dynamic New World: Refining Our View of Protein Structure, Function and Evolution.

Proteins are crucial to the functioning of all lifeforms. Traditional understanding posits that a single protein occupies a single structure ("fold"), which performs a single function. This view is radically challenged with the recognition that high structural dynamism-the capacity to be extra "floppy"-is more prevalent in functional proteins than previously assumed. As reviewed here, this dynamic take on proteins affects our understanding of protein "structure", function, and evolution, and even gives us a glimpse into protein origination. Specifically, this review will discuss historical developments concerning protein structure, and important new relationships between dynamism and aspects of protein sequence, structure, binding modes, binding promiscuity, evolvability, and origination. Along the way, suggestions will be provided for how key parts of textbook definitions-that so far have excluded membership to intrinsically disordered proteins (IDPs)-could be modified to accommodate our more dynamic understanding of proteins.

Origination of the Protein Fold Repertoire from Oily Pluripotent Peptides.

While the repertoire of protein folds that exists today underlies most of life's capabilities, our mechanistic picture of protein fold origination is incomplete. This paper discusses a hypothetical mechanism for the emergence of the protein fold repertoire from highly dynamic and collapsed peptides, exemplified by peptides with high oil content or hydrophobicity. These peptides are called pluripotent to emphasize their capacity to evolve into numerous folds transiently available to them. As evidence, the paper will discuss previous simulation work on the superior fold evolvability of oily peptides, trace ("fossil") evidence within proteomes seen today, and a general relationship between protein dynamism and evolvability. Aside from implications on the origination of protein folds, the hypothesis implies that the vanishing utility of a random peptide in protein origination may be relatively exaggerated, as some random peptides with a certain composition (e.g., oily) may fare better than others. In later sections, the hypothesis is discussed in the context of existing discussions regarding the spontaneous origination of biomolecules.

Development and use of an atomistic CHARMM-based forcefield for peptoid simulation.

Peptoids are positional isomers of peptides: peptoid sidechains are attached to backbone nitrogens rather than α-carbons. Peptoids constitute a class of sequence-specific polymers resistant to biological degradation and potentially as diverse, structurally and functionally, as proteins. While molecular simulation of proteins is commonplace, relatively few tools are available for peptoid simulation. Here, we present a first-generation atomistic forcefield for peptoids. Our forcefield is based on the peptide forcefield CHARMM22, with key parameters tuned to match both experimental data and quantum mechanical calculations for two model peptoids (dimethylacetamide and a sarcosine dipeptoid). We used this forcefield to demonstrate that solvation of a dipeptoid substantially modifies the conformations it can access. We also simulated a crystal structure of a peptoid homotrimer, H-(N-2-phenylethyl glycine)3 -OH, and we show that experimentally observed structural and dynamical features of the crystal are accurately described by our forcefield. The forcefield presented here provides a starting point for future development of peptoid-specific simulation methods within CHARMM.

Two modes of protein sequence evolution and their compositional dependencies.

Protein sequence evolution has resulted in a vast repertoire of molecular functionality crucial to life. Despite the central importance of sequence evolution to biology, our fundamental understanding of how sequence composition affects evolution is incomplete. This report describes the utilization of lattice model simulations of directed evolution, which indicate that, on average, peptide and protein evolvability is strongly dependent on initial sequence composition. The report also discusses two distinct regimes of sequence evolution by point mutation: (a) the "classical" mode where sequences "crawl" over free energy barriers towards acquiring a target fold, and (b) the "quantum" mode where sequences appear to "tunnel" through large energy barriers generally insurmountable by means of a crawl. Finally, the simulations indicate that oily and charged peptides are the most efficient substrates for evolution at the "classical" and "quantum" regimes, respectively, and that their respective response to temperature is commensurate with analogies made to barrier crossing in classical and quantum systems. On the whole, these results show that sequence composition can tune both the evolvability and the optimal mode of evolution of peptides and proteins.