Large-area optical metasurface fabrication using nanostencil lithography.

We demonstrate a large-area fabrication process for optical metasurfaces utilizing reusable SiN on Si nanostencils. To improve the yield of the nanostencil fabrication, we partially etch the front-side SiN layer to transfer the metasurface pattern from the resist to the nanostencil membrane, preserving the integrity of the membrane during the subsequent potassium hydroxide etch. To enhance the reliability and resolution of metasurface fabrication using the nanostencil, we spin coat a sacrificial layer of resist to precisely determine the gap between the nanostencil and the metasurface substrate for the subsequent liftoff. 1.5 mm diameter PbTe meta-lenses on ${\rm{Ca}}{{\rm{F}}_2}$ fabricated using nanostencils show diffraction-limited focusing and focusing efficiencies of 42% for a 2 mm focal length lens and 53% for a 4 mm focal length lens. The nanostencils can also be cleaned using chemical cleaning methods for reuse.

Mitochondrial complex I abnormalities is associated with tau and clinical symptoms in mild Alzheimer's disease.

BACKGROUND: Mitochondrial electron transport chain abnormalities have been reported in postmortem pathological specimens of Alzheimer's disease (AD). However, it remains unclear how amyloid and tau are associated with mitochondrial dysfunction in vivo. The purpose of this study is to assess the local relationships between mitochondrial dysfunction and AD pathophysiology in mild AD using the novel mitochondrial complex I PET imaging agent [18F]BCPP-EF. METHODS: Thirty-two amyloid and tau positive mild stage AD dementia patients (mean age ± SD: 71.1 ± 8.3 years) underwent a series of PET measurements with [18F]BCPP-EF mitochondrial function, [11C]PBB3 for tau deposition, and [11C] PiB for amyloid deposition. Age-matched normal control subjects were also recruited. Inter and intrasubject comparisons of levels of mitochondrial complex I activity, amyloid and tau deposition were performed. RESULTS: The [18F]BCPP-EF uptake was significantly lower in the medial temporal area, highlighting the importance of the mitochondrial involvement in AD pathology. [11C]PBB3 uptake was greater in the temporo-parietal regions in AD. Region of interest analysis in the Braak stage I-II region showed significant negative correlation between [18F]BCPP-EF SUVR and [11C]PBB3 BPND (R = 0.2679, p = 0.04), but not [11C] PiB SUVR. CONCLUSIONS: Our results indicated that mitochondrial complex I is closely associated with tau load evaluated by [11C]PBB3, which might suffer in the presence of its off-target binding. The absence of association between mitochondrial complex I dysfunction with amyloid load suggests that mitochondrial dysfunction in the trans-entorhinal and entorhinal region is a reflection of neuronal injury occurring in the brain of mild AD.

Reconfigurable all-dielectric metalens with diffraction-limited performance.

Active metasurfaces, whose optical properties can be modulated post-fabrication, have emerged as an intensively explored field in recent years. The efforts to date, however, still face major performance limitations in tuning range, optical quality, and efficiency, especially for non-mechanical actuation mechanisms. In this paper, we introduce an active metasurface platform combining phase tuning in the full 2π range and diffraction-limited performance using an all-dielectric, low-loss architecture based on optical phase change materials (O-PCMs). We present a generic design principle enabling binary switching of metasurfaces between arbitrary phase profiles and propose a new figure-of-merit (FOM) tailored for reconfigurable meta-optics. We implement the approach to realize a high-performance varifocal metalens operating at 5.2 µm wavelength. The reconfigurable metalens features a record large switching contrast ratio of 29.5 dB. We further validate aberration-free and multi-depth imaging using the metalens, which represents a key experimental demonstration of a non-mechanical tunable metalens with diffraction-limited performance.

Single-Element Diffraction-Limited Fisheye Metalens.

Wide field-of-view (FOV) optical functionality is crucial for implementation of advanced imaging and image projection devices. Conventionally, wide FOV operation is attained with complicated assembly of multiple optical elements known as "fisheye lenses". Here we present a novel metalens design capable of performing diffraction-limited focusing and imaging over an unprecedented near 180° angular FOV. The lens is monolithically integrated on a one-piece flat substrate and involves only a single layer of metasurface that corrects third-order Seidel aberrations including coma, astigmatism, and field curvature. The metalens further features a planar focal surface, which enables considerably simplified system architectures for applications in imaging and projection. We fabricated the metalens using Huygens meta-atoms operating at 5.2 µm wavelength and experimentally demonstrated aberration-free focusing and imaging over the entire FOV. The design concept is generic and can be readily adapted to different meta-atom geometries and wavelength ranges to meet diverse application demands.

Sleep Parameters and Overnight Urinary Melatonin Production in Children With Persistent Post-concussion Symptoms.

BACKGROUND: Sleep disturbance is common after a mild traumatic brain injury (mTBI) in children, yet its biology is poorly understood. We aimed to explore sleep-related problems (SRPs), sleep-activity patterns, and endogenous melatonin production in children with different recovery trajectories following mTBI. We hypothesized that children with delayed recovery would have more SRPs and abnormal sleep-activity patterns, which would correlate with lower overnight melatonin production. METHODS: In this prospective controlled cohort study, we enrolled 83 children with persistent symptoms, 26 children who had clinically recovered following mTBI, and 25 healthy controls. SRPs were evaluated using the sleep subscale of the Post-Concussion Symptom Inventory. Sleep actigraphy was performed for five to seven days at 37 (S.D. 7) days post-injury. Health-related quality of life and mood disturbance was assessed using the Child Health Questionnaire and the Behavior Assessment System for Children, respectively. Endogenous melatonin production was assessed using overnight urine collection. RESULTS: The groups were similar in age (13.9 [S.D. 2.6] years) and sex (52% female). Regression analysis demonstrated increased SRP in the symptomatic group (9.0; 95% confidence interval: 7.6, 11.1) compared with the recovered group (1.6; 95% confidence interval: 1.0, 2.4) and controls (2.0; 95% confidence intervals: 1.2, 3.2). Actigraphy parameters and urinary melatonin levels were not significantly different between groups. Neither SRPs nor actigraphy parameters correlated with anxiety and depression scores. CONCLUSIONS: Although children with persistent post-concussion symptoms reported more SRPs, this was not related to actigraphy sleep parameters or melatonin production. Further research is warranted to understand the pathophysiology of post-traumatic sleep disturbance.

Visual perspective taking in young and older adults.

Advanced age is associated with difficulties in social understanding. However, little is known about the underlying cognitive processes. In the present study, healthy young and older adults completed measures of implicit and explicit visual perspective taking (VPT) and measures of executive and social cognition across four experiments. Congruency effects (slower response times or reduced accuracy when scenes were incongruent with the alternate perspective) were identified for the egocentric ("self") and allocentric ("other") conditions of both Level 1 ("line of sight") and Level 2 ("egocentric transformation") explicit VPT. Older adults showed less influence of the alternate perspective during Level 1 VPT, as indexed by fewer errors when the alternate perspective was incongruent. However, during Level 2 VPT, compared with young adults, older adults showed greater influence of the allocentric perspective during egocentric judgments as indexed by slower response times when the scene was incongruent with the allocentric perspective. Older adults were also slower at taking the allocentric perspective in general across both Level 1 and 2 tasks. An implicit VPT effect was identified that was consistent across both age groups. Several VPT measures were associated with executive and social cognition, with different patterns in young and older adults suggesting differing underlying strategies or cognitive processes may partially explain VPT differences between the groups. Difficulties in higher order social tasks may arise from underlying cognitive processes involved in perspective taking and these may be different depending on the requirement to perform an egocentric transformation into the allocentric frame of reference. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Development of novel metabolite-responsive transcription factors via transposon-mediated protein fusion.

Naturally evolved metabolite-responsive biosensors enable applications in metabolic engineering, ranging from screening large genetic libraries to dynamically regulating biosynthetic pathways. However, there are many metabolites for which a natural biosensor does not exist. To address this need, we developed a general method for converting metabolite-binding proteins into metabolite-responsive transcription factors-Biosensor Engineering by Random Domain Insertion (BERDI). This approach takes advantage of an in vitro transposon insertion reaction to generate all possible insertions of a DNA-binding domain into a metabolite-binding protein, followed by fluorescence activated cell sorting to isolate functional biosensors. To develop and evaluate the BERDI method, we generated a library of candidate biosensors in which a zinc finger DNA-binding domain was inserted into maltose binding protein, which served as a model well-studied metabolite-binding protein. Library diversity was characterized by several methods, a selection scheme was deployed, and ultimately several distinct and functional maltose-responsive transcriptional biosensors were identified. We hypothesize that the BERDI method comprises a generalizable strategy that may ultimately be applied to convert a wide range of metabolite-binding proteins into novel biosensors for applications in metabolic engineering and synthetic biology.

Modeling and validation of autoinducer-mediated bacterial gene expression in microfluidic environments.

Biosensors exploiting communication within genetically engineered bacteria are becoming increasingly important for monitoring environmental changes. Currently, there are a variety of mathematical models for understanding and predicting how genetically engineered bacteria respond to molecular stimuli in these environments, but as sensors have miniaturized towards microfluidics and are subjected to complex time-varying inputs, the shortcomings of these models have become apparent. The effects of microfluidic environments such as low oxygen concentration, increased biofilm encapsulation, diffusion limited molecular distribution, and higher population densities strongly affect rate constants for gene expression not accounted for in previous models. We report a mathematical model that accurately predicts the biological response of the autoinducer N-acyl homoserine lactone-mediated green fluorescent protein expression in reporter bacteria in microfluidic environments by accommodating these rate constants. This generalized mass action model considers a chain of biomolecular events from input autoinducer chemical to fluorescent protein expression through a series of six chemical species. We have validated this model against experimental data from our own apparatus as well as prior published experimental results. Results indicate accurate prediction of dynamics (e.g., 14% peak time error from a pulse input) and with reduced mean-squared error with pulse or step inputs for a range of concentrations (10 µM-30 µM). This model can help advance the design of genetically engineered bacteria sensors and molecular communication devices.

Development of a broad-host synthetic biology toolbox for Ralstonia eutropha and its application to engineering hydrocarbon biofuel production.

BACKGROUND: The chemoautotrophic bacterium Ralstonia eutropha can utilize H2/CO2 for growth under aerobic conditions. While this microbial host has great potential to be engineered to produce desired compounds (beyond polyhydroxybutyrate) directly from CO2, little work has been done to develop genetic part libraries to enable such endeavors. RESULTS: We report the development of a toolbox for the metabolic engineering of Ralstonia eutropha H16. We have constructed a set of broad-host-range plasmids bearing a variety of origins of replication, promoters, 5' mRNA stem-loop structures, and ribosomal binding sites. Specifically, we analyzed the origins of replication pCM62 (IncP), pBBR1, pKT (IncQ), and their variants. We tested the promoters P(BAD), T7, P(xyls/PM), P(lacUV5), and variants thereof for inducible expression. We also evaluated a T7 mRNA stem-loop structure sequence and compared a set of ribosomal binding site (RBS) sequences derived from Escherichia coli, R. eutropha, and a computational RBS design tool. Finally, we employed the toolbox to optimize hydrocarbon production in R. eutropha and demonstrated a 6-fold titer improvement using the appropriate combination of parts. CONCLUSION: We constructed and evaluated a versatile synthetic biology toolbox for Ralstonia eutropha metabolic engineering that could apply to other microbial hosts as well.