Site-specific N-alkylation of DNA oligonucleotide nucleobases by DNAzyme-catalyzed reductive amination.

DNA and RNA nucleobase modifications are biologically relevant and valuable in fundamental biochemical and biophysical investigations of nucleic acids. However, directly introducing site-specific nucleobase modifications into long unprotected oligonucleotides is a substantial challenge. In this study, we used in vitro selection to identify DNAzymes that site-specifically N-alkylate the exocyclic nucleobase amines of particular cytidine, guanosine, and adenosine (C, G and A) nucleotides in DNA substrates, by reductive amination using a 5'-benzaldehyde oligonucleotide as the reaction partner. The new DNAzymes each require one or more of Mg2+, Mn2+, and Zn2+ as metal ion cofactors and have kobs from 0.04 to 0.3 h-1, with rate enhancement as high as ∼104 above the splinted background reaction. Several of the new DNAzymes are catalytically active when an RNA substrate is provided in place of DNA. Similarly, several new DNAzymes function when a small-molecule benzaldehyde compound replaces the 5'-benzaldehyde oligonucleotide. These findings expand the scope of DNAzyme catalysis to include nucleobase N-alkylation by reductive amination. Further development of this new class of DNAzymes is anticipated to facilitate practical covalent modification and labeling of DNA and RNA substrates.

Third-party arbitration and forgiving strategies increase cooperation when perception errors are common.

Humans cooperate in groups in which mutual monitoring is common, and this provides the possibility of third-party arbitration. Third-party arbitration stabilizes reciprocity in at least two ways: first, when it is accurate, it reduces the frequency of misunderstandings resulting from perception errors, and second, even when it is inaccurate, it provides a public signal that allows pairs to align their expectations about how to behave after errors occur. Here, we describe experiments that test for these two effects. We find that in an iterated, sequential Prisoner's Dilemma game with errors, players with the highest average payoffs are those who make use of third-party arbitration and who also employ forgiving strategies. The combination of these two behaviours reduces the detrimental effects of errors on reciprocity, resulting in more cooperation.

Interactions of Fundamental Mie Modes with Thin Epsilon-near-Zero Substrates.

Extensive research has focused on Mie modes in dielectric nanoresonators, enabling the creation of thin optical devices surpassing their bulk counterparts. This study investigates the interactions between two fundamental Mie modes, electric and magnetic dipoles, and the epsilon-near-zero (ENZ) mode. Analytical, simulation, and experimental analyses reveal that the presence of the ENZ substrate significantly modifies these modes despite a large size mismatch. Electric and magnetic dipole modes, both with ∼12 THz line widths, exhibit 21 and 26 THz anticrossings, respectively, when coupled to the ENZ mode, indicating strong coupling. We also demonstrate that this strongly coupled system yields notably large subpicosecond nonlinear responses. Our results establish a solid foundation for designing functional, nonlinear, dynamic dielectric metasurfaces with ENZ materials.

DNAzyme-Catalyzed Site-Specific N-Acylation of DNA Oligonucleotide Nucleobases.

We used in vitro selection to identify DNAzymes that acylate the exocyclic nucleobase amines of cytidine, guanosine, and adenosine in DNA oligonucleotides. The acyl donor was the 2,3,5,6-tetrafluorophenyl ester (TFPE) of a 5'-carboxyl oligonucleotide. Yields are as high as >95 % in 6 h. Several of the N-acylation DNAzymes are catalytically active with RNA rather than DNA oligonucleotide substrates, and eight of nine DNAzymes for modifying C are site-specific (>95 %) for one particular substrate nucleotide. These findings expand the catalytic ability of DNA to include site-specific N-acylation of oligonucleotide nucleobases. Future efforts will investigate the DNA and RNA substrate sequence generality of DNAzymes for oligonucleotide nucleobase N-acylation, toward a universal approach for site-specific oligonucleotide modification.

Using an acousto-optic modulator as a fast spatial light modulator.

High-speed spatial light modulators (SLM) are crucial components for free-space communication and structured illumination imaging. Current approaches for dynamical spatial mode generation, such as liquid crystal SLMs or digital micromirror devices, are limited to a maximum pattern refresh rate of 10 kHz and have a low damage threshold. We demonstrate that arbitrary spatial profiles in a laser pulse can be generated by mapping the temporal radio-frequency (RF) waveform sent to an acousto-optic modulator (AOM) onto the optical field. We find that the fidelity of the SLM performance can be improved through numerical optimization of the RF waveform to overcome the nonlinear effect of AOM. An AOM can thus be used as a 1-dimensional SLM, a technique we call acousto-optic spatial light modulator (AO-SLM), which has 50 µm pixel pitch, over 1 MHz update rate, and high damage threshold. We simulate the application of AO-SLM to single-pixel imaging, which can reconstruct a 32×32 pixel complex object at a rate of 11.6 kHz with 98% fidelity.

Orthogonal spatial coding with stimulated parametric down-conversion.

Orthogonal optical coding is widely used in classical multi-user communication networks. Using the phase conjugation property of stimulated parametric down-conversion, we extend the current time-domain orthogonal optical coding scheme to the spatial domain to encode and decode image information. In this process, the idler beam inherits the complex conjugate of the field information encoded in the seed beam. An encoding phase mask introduced onto the input seed beam blurs the image transferred to the idler. The original image is restored by passing the coded transferred image through a corrective phase mask placed in the momentum space of the idler beam. We expect that this scheme can also inspire new techniques in secure image transmission, aberration cancellation, and frequency conversion imaging.

Optically tunable bianisotropy in a sphere made from an epsilon-near-zero material.

Bianisotropic media can be used to engineer absorbance, scattering, polarization, and dispersion of electromagnetic waves. However, the demonstration of a tunable light-induced bianisotropy at optical frequencies is still lacking. Here, we propose an experimentally feasible concept for a light-induced tunable bianisotropic response in a homogeneous sphere made of an epsilon-near-zero (ENZ) material. By exploiting the large linear absorption and the large possible intensity-dependent changes in the permittivity of ENZ materials, the direction-dependent scattering and absorption cross sections could be obtained. Our findings pave the way for further studies and applications in the optical regime requiring full dynamic control of the bianisotropic behavior.

Automatic turbulence mitigation for coherent free-space optical links using crystal-based phase conjugation and fiber-coupled data modulation.

There are various performance advantages when using temporal phase-based data encoding and coherent detection with a local oscillator (LO) in free-space optical (FSO) links. However, atmospheric turbulence can cause power coupling from the Gaussian mode of the data beam to higher-order modes, resulting in significantly degraded mixing efficiency between the data beam and a Gaussian LO. Photorefractive crystal-based self-pumped phase conjugation has been previously demonstrated to "automatically" mitigate turbulence with limited-rate free-space-coupled data modulation (e.g., <1 Mbit/s). Here, we demonstrate automatic turbulence mitigation in a 2-Gbit/s quadrature-phase-shift-keying (QPSK) coherent FSO link using degenerate four-wave-mixing (DFWM)-based phase conjugation and fiber-coupled data modulation. Specifically, we counter-propagate a Gaussian probe from the receiver (Rx) to the transmitter (Tx) through turbulence. At the Tx, we generate a Gaussian beam carrying QPSK data by a fiber-coupled phase modulator. Subsequently, we create a phase conjugate data beam through a photorefractive crystal-based DFWM involving the Gaussian data beam, the turbulence-distorted probe, and a spatially filtered Gaussian copy of the probe beam. Finally, the phase conjugate beam is transmitted back to the Rx for turbulence mitigation. Compared to a coherent FSO link without mitigation, our approach shows up to ∼14-dB higher LO-data mixing efficiency and achieves error vector magnitude (EVM) performance of <16% under various turbulence realizations.

Short-term stability of anterior open bite treatment with clear aligners in adults.

INTRODUCTION: This study aimed to examine the stability of anterior open bite (AOB) treatment with clear aligners. METHODS: This retrospective cohort study included 52 adult AOB patients (aged >18 years; 15 males, 37 females) who underwent nonextraction clear aligner treatment and were at least 1 year posttreatment. Eleven cephalometric measurements were evaluated at pretreatment, end of active treatment, and at least 1-year posttreatment. Overbite change, the primary outcome variable, and other cephalometric changes during treatment and retention were calculated, and repeated measures analysis of variance were performed. Stepwise multiple regression was used to make a prediction equation for open bite relapse. RESULTS: The mean retention period was 2.1 ± 1.1 years. The mean change in overbite during treatment was 3.3 ± 1.5 mm; 6% of patients presented relapse at least 1 year after treatment completion. The mean change of overbite (0.2 ± 0.5 mm) during the retention period was not statistically significant (P = 0.59). None of the 11 cephalometric measurements showed significant change during the retention period. The prediction model showed that only the coefficient for a tongue posture issue at the initial examination was statistically significant. CONCLUSIONS: AOB was successfully corrected in all 52 patients using only clear aligners with no additional adjunctive aids such as microimplants. When retained with maxillary and mandibular fixed retainers and maxillary and mandibular vacuum-formed retainers, there was no significant change in cephalometric measurements during the short-term retention period.

Consumer? Views and preferences of people receiving public mental health care in Australia on the terms used to refer to them.

OBJECTIVES: To understand: a) whether adults receiving public mental health care were aware they were officially referred to as 'consumers' and, b) their views and preferences on the terms used to refer to them. METHODS: Single-page, anonymous survey conducted across two community mental health services in Northern New South Wales (NNSW). Ethics approval obtained from the local research office. RESULTS: 108 people completed the survey with a response rate of approximately 22%. The vast majority (77%) of respondents were not aware that they were officially referred to as 'consumers'. 32% of respondents disliked the term 'consumer' and 11% found it offensive. Half preferred the term 'patient', particularly when consulting a psychiatrist (55%). A small minority (5-7%) preferred the term 'consumer' for any care interaction. CONCLUSION: Most respondents in this survey wished to be referred to as a 'patient' and a large proportion disliked being referred to as a 'consumer' or found it offensive. Further surveys should include broader sociodemographic and diagnostic/treatment variables. Official terms used to refer to people receiving public mental health care should be person-centred and evidence based.

HVCN1 modulates BCR signal strength via regulation of BCR-dependent generation of reactive oxygen species.

Voltage-gated proton currents regulate generation of reactive oxygen species (ROS) in phagocytic cells. In B cells, stimulation of the B cell antigen receptor (BCR) results in the production of ROS that participate in B cell activation, but the involvement of proton channels is unknown. We report here that the voltage-gated proton channel HVCN1 associated with the BCR complex and was internalized together with the BCR after activation. BCR-induced generation of ROS was lower in HVCN1-deficient B cells, which resulted in attenuated BCR signaling via impaired BCR-dependent oxidation of the tyrosine phosphatase SHP-1. This resulted in less activation of the kinases Syk and Akt, impaired mitochondrial respiration and glycolysis and diminished antibody responses in vivo. Our findings identify unanticipated functions for proton channels in B cells and demonstrate the importance of ROS in BCR signaling and downstream metabolism.

Designing high-performance propagation-compressing spaceplates using thin-film multilayer stacks.

The development of metasurfaces has enabled unprecedented portability and functionality in flat optical devices. Spaceplates have recently been introduced as a complementary element to reduce the space between individual metalenses, which will further miniaturize entire imaging devices. However, spaceplates necessitate an optical response which depends on the transverse spatial frequency component of a light field - therefore making it challenging both to design them and to assess their ultimate performance and potential. Here, we employ inverse-design techniques to explore the behaviour of general thin-film-based spaceplates. We observe a tradeoff between the compression factor R and the numerical aperture NA of such devices; we obtained a compression factor of R=5.5 for devices with an NA = 0.42, and up to a record R=340 with NA of 0.017. Our work illustrates that even simple designs consisting of realistic materials (i.e., silicon and glass) permit capable spaceplates for monochromatic applications.

Cross-polarized surface lattice resonances in a rectangular lattice plasmonic metasurface.

Multiresonant metasurfaces could enable many applications in filtering, sensing, and nonlinear optics. However, developing a metasurface with more than one high-quality-factor or high-Q resonance at designated resonant wavelengths is challenging. Here, we experimentally demonstrate a plasmonic metasurface exhibiting different, narrow surface lattice resonances by exploiting the polarization degree of freedom where different lattice modes propagate along different dimensions of the lattice. The surface consists of aluminum nanostructures in a rectangular periodic lattice. The resulting surface lattice resonances were measured around 640 nm and 1160 nm with Q factors of ∼50 and ∼800, respectively. The latter is a record-high plasmonic Q factor within the near-infrared type-II window. Such metasurfaces could benefit such applications as frequency conversion and all-optical switching.

Suppression of Nonlinear Optical Rogue Wave Formation Using Polarization-Structured Beams.

A nonlinear self-focusing material can amplify random small-amplitude phase modulations present in an optical beam, leading to the formation of amplitude singularities commonly referred to as optical caustics. By imposing polarization structuring on the beam, we demonstrate the suppression of amplitude singularities caused by nonlinear self-phase modulation. Our results are the first to indicate that polarization-structured beams can suppress nonlinear caustic formation in a saturable self-focusing medium and add to the growing understanding of catastrophic self-focusing effects in beams containing polarization structure.

Relaxed Phase-Matching Constraints in Zero-Index Waveguides.

The utility of all parametric nonlinear optical processes is hampered by phase-matching requirements. Quasi-phase-matching, birefringent phase matching, and higher-order-mode phase matching have all been developed to address this constraint, but the methods demonstrated to date suffer from the inconvenience of only being phase matched for a single, specific arrangement of beams, typically copropagating, resulting in cumbersome experimental configurations and large footprints for integrated devices. Here, we experimentally demonstrate that these phase-matching requirements may be satisfied in a parametric nonlinear optical process for multiple, if not all, configurations of input and output beams when using low-index media. Our measurement constitutes the first experimental observation of direction-independent phase matching for a medium sufficiently long for phase matching to be relevant. We demonstrate four-wave mixing from spectrally distinct co- and counterpropagating pump and probe beams, the backward generation of a nonlinear signal, and excitation by an out-of-plane probe beam. These results explicitly show that the unique properties of low-index media relax traditional phase-matching constraints, which can be exploited to facilitate nonlinear interactions and miniaturize nonlinear devices, thus adding to the established exceptional properties of low-index materials.

Large-scale cooperation in small-scale foraging societies.

We present evidence that people in small-scale mobile hunter-gatherer societies cooperated in large numbers to produce collective goods. Foragers engaged in large-scale communal hunts and constructed shared capital facilities; they made shared investments in improving the local environment; and they participated in warfare, formed enduring alliances, and established trading networks. Large-scale collective action often played a crucial role in subsistence. The provision of public goods involved the cooperation of many individuals, so each person made only a small contribution. This evidence suggests that large-scale cooperation occurred in the Pleistocene societies that encompass most of human evolutionary history, and therefore it is unlikely that large-scale cooperation in Holocene food producing societies results from an evolved psychology shaped only in small-group interactions. Instead, large-scale human cooperation needs to be explained as an adaptation, likely rooted in distinctive features of human biology, grammatical language, increased cognitive ability, and cumulative cultural adaptation.

Generation of volumetrically full Poincaré beams.

Optical communications, remote sensing, particle trapping, and high-resolution imaging are a few research areas that benefit from new techniques to generate structured light. We present a method of generating polarization-structured laser beams that contain both full and partial polarization states. We demonstrate this method by generating an optical beam that contains every state of partial and full polarization. We refer to this beam as a volumetrically full Poincaré beam to distinguish it from full Poincaré beams, which contain all states of full polarization only. In contrast to methods relying upon spatial coherence to generate polarization-structured beams with partial polarization, our method creates well-collimated beams by relying upon temporal coherence.

Lung disease burden assessment by oscillometry in a systematically disadvantaged urban population experiencing homelessness or at-risk for homelessness in Ottawa, Canada from a prospective observational study.

RATIONALE: Oscillometry is an emerging technique that offers some advantages over spirometry as it does not require forced exhalation and may detect early changes in respiratory pathology. Obstructive lung disease disproportionately impacts people experiencing homelessness with a high symptoms burden, yet oscillometry is not studied in this population. OBJECTIVES: To assess lung disease and symptom burden using oscillometry in people experiencing homelessness or at-risk of homelessness using a community-based participatory action research approach (The Bridge Model™). METHODS: Of 80 recruited, 55 completed baseline oscillometry, 64 completed spirometry, and all completed patient-reported outcomes with demographics, health, and respiratory symptom related questionnaires in the Participatory Research in Ottawa: Management and Point-of-Care for Tobacco Dependence project. Using a two-tail t-test, we compared mean oscillometry values for airway resistance (R5-20), reactance area under the curve (Ax) and reactance at 5 Hz (X5) amongst individuals with fixed-ratio method (FEV1/FVC ratio < 0.70) and LLN (FEV1/FVC ratio ≤ LLN) spirometry diagnosed chronic obstructive pulmonary disease (COPD). We compared mean oscillometry parameters based on participants' COPD assessment test (CAT) scores using ANOVA test. RESULTS: There was no significant difference between the pre- and post- bronchodilator values of R5-20 and Ax for the fixed ratio method (p = 0.63 and 0.43) and the LLN method (p = 0.45 and 0.36). There was a significant difference in all three of the oscillometry parameters, R5-20, Ax and X5, based on CAT score (p = 0.009, 0.007 and 0.05, respectively). There was a significant difference in R5-20 and Ax based on the presence of phlegm (p = 0.03 and 0.02, respectively) and the presence of wheeze (p = 0.05 and 0.01, respectively). Oscillometry data did not correlate with spirometry data, but it was associated with CAT scores and correlated with the presence of self-reported symptoms of phlegm and wheeze in this population. CONCLUSIONS: Oscillometry is associated with respiratory symptom burden and highlights the need for future studies to generate more robust data regarding the use of oscillometry in systematically disadvantaged populations where disease burden is disproportionately higher than the general population. TRIAL REGISTRATION: ClinicalTrails.gov-NCT03626064, Retrospective registered: August 2018, https://clinicaltrials.gov/ct2/show/NCT03626064.

Adiabatic Frequency Conversion Using a Time-Varying Epsilon-Near-Zero Metasurface.

A time-dependent change in the refractive index of a material leads to a change in the frequency of an optical beam passing through that medium. Here, we experimentally demonstrate that this effect-known as adiabatic frequency conversion (AFC)-can be significantly enhanced by a nonlinear epsilon-near-zero-based (ENZ-based) plasmonic metasurface. Specifically, by using a 63-nm-thick metasurface, we demonstrate a large, tunable, and broadband frequency shift of up to ∼11.2 THz with a pump intensity of 4 GW/cm2. Our results represent a decrease of ∼10 times in device thickness and 120 times in pump peak intensity compared with the cases of bare, thicker ENZ materials for the similar amount of frequency shift. Our findings might potentially provide insights for designing efficient time-varying metasurfaces for the manipulation of ultrafast pulses.

Comparison between a human judge and automatic landmark identification on digital models.

INTRODUCTION: Accurate landmark identification is a prerequisite for accurate and reliable biomedical image analysis. Orthodontic study models are valuable tools for diagnosis, treatment planning, and maintaining complete records. The purpose of this study was to evaluate the reliability and validity of a software program (Align Technology, Inc) as a tool for automatic landmark location. METHODS: Using digital intraoral scans of 10 dental arches, 4 calibrated human judges independently located cusp tips and interproximal contacts. The same landmarks were automatically identified by the software. Intraclass correlation coefficient (Cronbach α), absolute mean errors, and regression analysis were calculated. In addition, Bland-Altman 95% confidence limits were also applied to the data to graphically display agreement on landmark identification between the human judges and the software. RESULTS: The intraclass correlation coefficient between the software and the human judges' average for the x-, y-, and z-coordinates for all landmarks was excellent, at 1.0, 1.0, and 0.98, respectively. The regression analysis and Bland-Altman plots show no systematic errors for agreement on landmark identification between the human judges and the software. CONCLUSIONS: Landmark location was nearly identical between the software and the human judges, making the methods interchangeable.