Fiber-taper collected emission from NV centers in high-Q/V diamond microdisks.

Fiber-coupled microdisks are a promising platform for enhancing the spontaneous emission from color centers in diamond. The measured cavity-enhanced emission from the microdisk is governed by the effective volume (V) of each cavity mode, the cavity quality factor (Q), and the coupling between the microdisk and the fiber. Here we observe room temperature photoluminescence from an ensemble of nitrogen-vacancy centers into high Q/V microdisk modes, which when combined with coherent spectroscopy of the microdisk modes, allows us to elucidate the relative contributions of these factors.

Bullseye dielectric cavities for photon collection from a surface-mounted quantum-light-emitter.

Coupling light from a point source to a propagating mode is an important problem in nano-photonics and is essential for many applications in quantum optics. Circular "bullseye" cavities, consisting of concentric rings of alternating refractive index, are a promising technology that can achieve near-unity coupling into a first lens. Here we design a bullseye structure suitable for enhancing the emission from dye molecules, 2D materials and nano-diamonds positioned on the surface of these cavities.

Super-Poissonian Light Statistics from Individual Silicon Vacancy Centers Coupled to a Laser-Written Diamond Waveguide.

Modifying light fields at the single-photon level is a key challenge for upcoming quantum technologies and can be realized in a scalable manner through integrated quantum photonics. Laser-written diamond photonics offers 3D fabrication capabilities and large mode-field diameters matched to fiber optic technology, though limiting the cooperativity at the single-emitter level. To realize large coupling efficiencies, we combine excitation of single shallow-implanted silicon vacancy centers via high numerical aperture optics with detection assisted by laser-written type-II waveguides.

Differential co-expression networks of the gut microbiota are associated with depression and anxiety treatment resistance among psychiatric inpatients.

Background: Comorbid anxiety and depression are common and are associated with greater disease burden than either alone. Our recent efforts have identified an association between gut microbiota dysfunction and severity of anxiety and depression. In this follow-up, we applied Differential Co-Expression Analysis (DiffCoEx) to identify potential gut microbiota biomarker(s) candidates of treatment resistance among psychiatric inpatients.

Functional Rehabilitation: An Integrated Treatment Model for Patients With Complex Physical and Psychiatric Conditions.

The health care delivery system in the United States, structured to provide single-disease care, presents unique challenges for patients with complex physical and psychiatric comorbidities. Patients in these populations are often referred to multiple specialty clinics, encounter little continuity of care or collaboration among their providers, incur high health care costs, and experience poor treatment outcomes. Given these barriers, questions remain about the extent to which siloed and fragmented care, as opposed to the complex nature of the illnesses themselves, contribute to poor outcomes.

Room-Temperature Quantum Emitter in Aluminum Nitride.

A device that is able to produce single photons is a fundamental building block for a number of quantum technologies. Significant progress has been made in engineering quantum emission in the solid state, for instance, using semiconductor quantum dots as well as defect sites in bulk and two-dimensional materials. Here we report the discovery of a room-temperature quantum emitter embedded deep within the band gap of aluminum nitride.

Fabrication of hybrid Fabry-Pérot microcavity using two-photon lithography for single-photon sources.

For an efficient single-photon source a high-count rate into a well-defined spectral and spatial mode is desirable. Here we have developed a hybrid planar Fabry-Pérot microcavity by using a two-photon polymerization process (2PP) where coupling between single-photon sources (diamond colour centres) and resonance modes is observed. The first step consists of using the 2PP process to build a polymer table structure around previously characterized nitrogen-vacancy (NV) centres on top of a distributed Bragg reflector (DBR) with a high reflectivity at the NV zero-phonon line (ZPL).

All-atom virus simulations.

The constant threat of viral disease can be combated by the development of novel vaccines and therapeutics designed to disrupt key features of virus structure or infection cycle processes. Such development relies on high-resolution characterization of viruses and their dynamical behaviors, which are often challenging to obtain solely by experiment. In response, all-atom molecular dynamics simulations are widely leveraged to study the structural components of viruses, leading to some of the largest simulation endeavors undertaken to date.

Assembly Properties of Hepatitis B Virus Core Protein Mutants Correlate with Their Resistance to Assembly-Directed Antivirals.

The hepatitis B virus (HBV) capsid or core protein (Cp) can self-assemble to form an icosahedral capsid. It is now being pursued as a target for small-molecule antivirals that enhance the rate and extent of its assembly to yield empty and/or aberrant capsids. These small molecules are thus called core protein allosteric modulators (CpAMs).

Integrated waveguides and deterministically positioned nitrogen vacancy centers in diamond created by femtosecond laser writing.

Diamond's nitrogen vacancy (NV) center is an optically active defect with long spin coherence times, showing great potential for both efficient nanoscale magnetometry and quantum information processing schemes. Recently, both the formation of buried 3D optical waveguides and high-quality single NVs in diamond were demonstrated using the versatile femtosecond laser-writing technique. However, until now, combining these technologies has been an outstanding challenge.

All-atom molecular dynamics of the HBV capsid reveals insights into biological function and cryo-EM resolution limits.

The hepatitis B virus capsid represents a promising therapeutic target. Experiments suggest the capsid must be flexible to function; however, capsid structure and dynamics have not been thoroughly characterized in the absence of icosahedral symmetry constraints. Here, all-atom molecular dynamics simulations are leveraged to investigate the capsid without symmetry bias, enabling study of capsid flexibility and its implications for biological function and cryo-EM resolution limits.

Molecular Dynamics Simulations of Protein-Drug Complexes: A Computational Protocol for Investigating the Interactions of Small-Molecule Therapeutics with Biological Targets and Biosensors.

MD simulations provide a powerful tool for the investigation of protein-drug complexes. The following chapter uses the aryl acylamidase-acetaminophen system as an example to describe a general protocol for preparing and running simulations of protein-drug complexes, complete with a step-by-step tutorial. The described approach is broadly applicable toward the study of drug interactions in the context of both biological targets and biosensing enzymes.

New insights into influenza A specificity: an evolution of paradigms.

Understanding the molecular origin of influenza receptor specificity is complicated by the paucity of quantitative affinity measurements, and the qualitative and variable nature of glycan array data. Further obstacles arise from the varied impact of viral glycosylation and the relatively narrow spectrum of biologically relevant receptors present on glycan arrays. A survey of receptor conformational properties is presented, leading to the conclusion that conformational entropy plays a key role in defining specificity, as does the newly reported ability of biantennary receptors that terminate in Siaα2-6Gal sequences to form bidentate interactions to two binding sites in a hemagglutinin trimer.

Angular measurements of the dynein ring reveal a stepping mechanism dependent on a flexible stalk.

The force-generating mechanism of dynein differs from the force-generating mechanisms of other cytoskeletal motors. To examine the structural dynamics of dynein's stepping mechanism in real time, we used polarized total internal reflection fluorescence microscopy with nanometer accuracy localization to track the orientation and position of single motors. By measuring the polarized emission of individual quantum nanorods coupled to the dynein ring, we determined the angular position of the ring and found that it rotates relative to the microtubule (MT) while walking.

Diamond photonics platform enabled by femtosecond laser writing.

Diamond is a promising platform for sensing and quantum processing owing to the remarkable properties of the nitrogen-vacancy (NV) impurity. The electrons of the NV center, largely localized at the vacancy site, combine to form a spin triplet, which can be polarized with 532 nm laser light, even at room temperature. The NV's states are isolated from environmental perturbations making their spin coherence comparable to trapped ions.

Computational Methodologies for Real-Space Structural Refinement of Large Macromolecular Complexes.

The rise of the computer as a powerful tool for model building and refinement has revolutionized the field of structure determination for large biomolecular systems. Despite the wide availability of robust experimental methods capable of resolving structural details across a range of spatiotemporal resolutions, computational hybrid methods have the unique ability to integrate the diverse data from multimodal techniques such as X-ray crystallography and electron microscopy into consistent, fully atomistic structures. Here, commonly employed strategies for computational real-space structural refinement are reviewed, and their specific applications are illustrated for several large macromolecular complexes: ribosome, virus capsids, chemosensory array, and photosynthetic chromatophore.

All-Atom Molecular Dynamics of Virus Capsids as Drug Targets.

Virus capsids are protein shells that package the viral genome. Although their morphology and biological functions can vary markedly, capsids often play critical roles in regulating viral infection pathways. A detailed knowledge of virus capsids, including their dynamic structure, interactions with cellular factors, and the specific roles that they play in the replication cycle, is imperative for the development of antiviral therapeutics.

Graphene oxide nanocapsules within silanized hydrogels suitable for electrochemical pseudocapacitors.

Soft biocompatible gels comprised of rolled up graphene oxide nanocapsules within the pores of silanized hydrogels may be used as electrochemical pseudocapacitors with physiological glucose or KOH as a reducing agent, affording a material suitable for devices requiring pulses with characteristic time less than a second.

Calculating binding free energies for protein-carbohydrate complexes.

A variety of computational techniques may be applied to compute theoretical binding free energies for protein-carbohydrate complexes. Elucidation of the intermolecular interactions, as well as the thermodynamic effects, that contribute to the relative strength of receptor binding can shed light on biomolecular recognition, and the resulting initiation or inhibition of a biological process. Three types of free energy methods are discussed here, including MM-PB/GBSA, thermodynamic integration, and a non-equilibrium alternative utilizing SMD.

Persistent pain after spinal cord injury is maintained by primary afferent activity.

Chronic pain caused by insults to the CNS (central neuropathic pain) is widely assumed to be maintained exclusively by central mechanisms. However, chronic hyperexcitablility occurs in primary nociceptors after spinal cord injury (SCI), suggesting that SCI pain also depends upon continuing activity of peripheral sensory neurons. The present study in rats (Rattus norvegicus) found persistent upregulation after SCI of protein, but not mRNA, for a voltage-gated Na(+) channel, Nav1.

Effect of microfibril twisting on theoretical powder diffraction patterns of cellulose Iβ.

Previous studies of calculated diffraction patterns for cellulose crystallites suggest that distortions that arise once models have been subjected to MD simulation are the result of both microfibril twisting and changes in unit cell dimensions induced by the empirical force field; to date, it has not been possible to separate the individual contributions of these effects. To provide a better understanding of how twisting manifests in diffraction data, the present study demonstrates a method for generating twisted and linear cellulose structures that can be compared without the bias of dimensional changes, allowing assessment of the impact of twisting alone. Analysis of unit cell dimensions, microfibril volume, hydrogen bond patterns, glycosidic torsion angles, and hydroxymethyl group orientations confirmed that the twisted and linear structures collected with this method were internally consistent, and theoretical powder diffraction patterns for the two were shown to be effectively indistinguishable.

On-chip manipulation of single photons from a diamond defect.

Operating reconfigurable quantum circuits with single photon sources is a key goal of photonic quantum information science and technology. We use an integrated waveguide device containing directional couplers and a reconfigurable thermal phase controller to manipulate single photons emitted from a chromium related color center in diamond. Observation of both a wavelike interference pattern and particlelike sub-Poissionian autocorrelation functions demonstrates coherent manipulation of single photons emitted from the chromium related center and verifies wave particle duality.

Action of octopamine and tyramine on muscles of Drosophila melanogaster larvae.

Octopamine (OA) and tyramine (TA) play important roles in homeostatic mechanisms, behavior, and modulation of neuromuscular junctions in arthropods. However, direct actions of these amines on muscle force production that are distinct from effects at the neuromuscular synapse have not been well studied. We utilize the technical benefits of the Drosophila larval preparation to distinguish the effects of OA and TA on the neuromuscular synapse from their effects on contractility of muscle cells.

Unraveling cellulose microfibrils: a twisted tale.

Molecular dynamics (MD) simulations of cellulose microfibrils are pertinent to the paper, textile, and biofuels industries for their unique capacity to characterize dynamic behavior and atomic-level interactions with solvent molecules and cellulase enzymes. While high-resolution crystallographic data have established a solid basis for computational analysis of cellulose, previous work has demonstrated a tendency for modeled microfibrils to diverge from the linear experimental structure and adopt a twisted conformation. Here, we investigate the dependence of this twisting behavior on computational approximations and establish the theoretical basis for its occurrence.