CRISPR/Cas12a Collateral Cleavage-Driven Transcription Amplification for Direct Nucleic Acid Detection.

The clustered regularly interspaced short palindromic repeat/Cas (CRISPR/Cas) system is a powerful tool for nucleic acid detection owing to specific recognition as well as cis- and trans-cleavage capabilities. However, the sensitivity of CRISPR/Cas-based diagnostic approaches is determined by nucleic acid preamplification, which has several limitations. Here, we present a method for direct nucleic acid detection without preamplification, by combining the CRISPR/Cas12a system with signal enhancement based on light-up RNA aptamer transcription. We first designed two DNA templates to transcribe the light-up RNA aptamer and kleptamer (Kb) RNA: the first DNA template encodes a Broccoli RNA aptamer for fluorescence signal generation, and the Kb DNA template comprises a dsDNA T7 promoter sequence and an ssDNA sequence that encodes an antisense strand for the Broccoli RNA aptamer. Hepatitis B virus (HBV) target recognition activates a CRISPR/Cas12a complex, leading to the catalytic cleavage of the ssDNA sequence. Transcription of the added Broccoli DNA template can then produce several Broccoli RNA aptamer transcripts for fluorescence enhancement. The proposed strategy exhibited excellent sensitivity and specificity with 22.4 fM detection limit, good accuracy, and stability for determining the target HBV dsDNA in human serum samples. Overall, this newly designed signal enhancement strategy can be employed as a universal sensing platform for ultrasensitive nucleic acid detection.

Wearable E-Textile and CNT Sensor Wireless Measurement System for Real-Time Penile Erection Monitoring.

Erection measurements are the most important indicator of male urological disease diagnosis, treatment, and results. Rigiscan has been used widely in studies and diagnoses for nocturnal penile tumescence for evaluating erectile dysfunction by measuring the number and timing of erectile dysfunctions during sleep. However, this device has limitations such as the weight and bulk of the device and has been questioned for its role as a standard for ED Erectile Dysfunction (ED) diagnosis. In this study, we propose a real-time wearable monitoring system that can quantitatively measure the length and circumference of the penis using electronic textiles (E-textile) and carbon nanotube (CNT) sensors. The E-textile sensor is used to measure the length, circumference, and gradient with portability, convenience, and comfort. Sensors were created by coating CNTs on latex for flexibility. The CNT-based latex condom-type sensor in our proposed system shows the length, circumference, and curvature measurements with changes in resistance, and the E-textile performance shows a 1.44% error rate and a cavity radius of 110 to 300. The results of this conceptual study are for supplementary sensor development with a combination of new technologies with alternatives or existing methods for measuring erection function.

Measurements of polarization-dependent angle-resolved light scattering from individual microscopic samples using Fourier transform light scattering.

We present a method to measure the vector-field light scattering of individual microscopic objects. The polarization-dependent optical field images are measured with quantitative phase imaging at the sample plane, and then numerically propagated to the far-field plane. This approach allows the two-dimensional polarization-dependent angle-resolved light scattered patterns from individual object to be obtained with high precision and sensitivity. Using this method, we present the measurements of the polarization-dependent light scattering of a liquid crystal droplet and individual silver nanowires over scattering angles of 50°. In addition, the spectroscopic extension of the polarization-dependent angle-resolved light scattering is demonstrated using wavelength-scanning illumination.

Long-range surface plasmon polariton detection with a graphene photodetector.

We present an integration of a single Ag nanowire (NW) with a graphene photodetector and demonstrate an efficient and compact detection of long-range surface plasmon polaritons (SPPs). Atomically thin graphene provides an ideal platform to detect the evanescent electric field of SPPs extremely bound at the interface of the Ag NW and glass substrate. Scanning photocurrent microscopy directly visualizes a polarization-dependent excitation and detects the SPPs. The SPP detection responsivity is readily controlled up to ∼17 mA/W by the drain-source voltage. We believe that the graphene SPP detector will be a promising building block for highly integrated photonic and optoelectronic circuits.

Rostral Agranular Insular Cortex Lesion with Motor Cortex Stimulation Enhances Pain Modulation Effect on Neuropathic Pain Model.

It is well known that the insular cortex is involved in the processing of painful input. The aim of this study was to evaluate the pain modulation role of the insular cortex during motor cortex stimulation (MCS). After inducing neuropathic pain (NP) rat models by the spared nerve injury method, we made a lesion on the rostral agranular insular cortex (RAIC) unilaterally and compared behaviorally determined pain threshold and latency in 2 groups: Group A (NP + MCS; n = 7) and Group B (NP + RAIC lesion + MCS; n = 7). Also, we simultaneously recorded neuronal activity (NP; n = 9) in the thalamus of the ventral posterolateral nucleus and RAIC to evaluate electrophysiological changes from MCS. The pain threshold and tolerance latency increased in Group A with "MCS on" and in Group B with or without "MCS on." Moreover, its increase in Group B with "MCS on" was more than that of Group B without MCS or of Group A, suggesting that MCS and RAIC lesioning are involved in pain modulation. Compared with the "MCS off" condition, the "MCS on" induced significant threshold changes in an electrophysiological study. Our data suggest that the RAIC has its own pain modulation effect, which is influenced by MCS.

On the neural implausibility of the modular mind: Evidence for distributed construction dissolves boundaries between perception, cognition, and emotion.

Firestone & Scholl (F&S) rely on three problematic assumptions about the mind (modularity, reflexiveness, and context-insensitivity) to argue cognition does not fundamentally influence perception. We highlight evidence indicating that perception, cognition, and emotion are constructed through overlapping, distributed brain networks characterized by top-down activity and context-sensitivity. This evidence undermines F&S's ability to generalize from case studies to the nature of perception.

Full three-dimensional power flow analysis of single-emitter-plasmonic-nanoantenna system.

We present a full three-dimensional (3D) power flow analysis of an emitter-nanoantenna system. A conventional analysis, based on the total Poynting vector, calculates only the coupling strength in terms of the Purcell enhancement. For a better understanding of the emitter-nanoantenna system, not only the Purcell enhancement but also complete information on the energy transfer channels is necessary. The separation of the pure scattering and emitter output Poynting vectors enables the quantification of the individual energy transfer channels. Employing the finite-difference time-domain method (FDTD), we examine a nanodisk antenna that supports the bright dipole and dark quadrupole resonance modes for which the power flow characteristics are completely distinct, and we analyze the power flow enhancements to the energy transfer channels with respect to the wavelength, polarization, and position of the emitter coupled to the antenna. The 3D power flow analysis reveals how the constructive or destructive interference between the emitter and the antenna resonance mode affects the power flow enhancements and the far-field radiation pattern. Our proposed power flow analysis should play a critical role in characterizing the emitter-antenna system and customizing its energy transfer properties for desired applications.

Transferrable superhydrophobic TiO2 nanorods on reduced graphene oxide films using block copolymer templates.

Superhydrophobic surfaces are normally fixed on the chosen materials. Here, we report transferrable superhydrophobicity which was enabled by fabricating TiO2 nanorods on a reduced graphene oxide (rGO) film. Superhydrophobic TiO2 nanorods were first synthesized from a nanoporous template of block copolymers (BCPs). The controllability over the dimension and shape of nanopores of the BCP template allowed for the adjustment of TiO2 nanostructures for superhydrophobicity. Since the rGO film provided effective transferring, TiO2 nanorods were conveyed onto a flexible polymer film and a metal substrate. Thus, the surface of the designated substrate was successfully changed to a superhydrophobic surface without alteration of its inherent characteristics.

Longitudinal FDG microPET imaging of neuropathic pain: does cerebellar activity correlate with neuropathic pain development in a rat model?

BACKGROUND: We used [F-18] FDG microPET imaging as part of a longitudinal study to investigate changes in the brain. METHODS: Glucose metabolism during the development of neuropathic pain after tibial and sural nerve transection (TST) model rats. MicroPET images were obtained 1 week before operation and then weekly for 8 weeks post-operation. RESULTS: The behavioral test was performed immediately after the every FDG administration. After TST modeling, neuropathic pain rats showed increased mechanical sensitivity of the injured hind paw. The withdrawal response to mechanical pain stimulation by von Frey filaments was observed within the first week (3.8 ± 0.73), and it rapidly increased in the third week (7.13 ± 0.82). This response reached a peak in the fourth week after surgery (9.0 ± 0.53), which persisted until the eighth week. In microPET scan imaging, cerebellum, which initially started from the ansiform lobule, was activated gradually to all part from the third week in all image acquisitions through the eighth week. CONCLUSIONS: The longitudinal microPET scan study of brains from neuropathic pain rat models showed sequential cerebellar activity that was in accordance with results from behavioral test responses, thus supporting a role for the cerebellum in the development of neuropathic pain.

Enhanced infrared neural stimulation using localized surface plasmon resonance of gold nanorods.

An advanced optical activation of neural tissues is demonstrated using pulsed infrared light and plasmonic gold nanorods. Photothermal effect localized in plasma membrane triggers action potentials of in vivo neural tissues. Compared with conventional infrared stimulation, the suggested method can increase a neural responsivity and lower a threshold stimulation level significantly, thereby reducing a requisite radiant exposure and the concern of tissue damage.

A liquid crystal polymer-based neuromodulation system: an application on animal model of neuropathic pain.

OBJECTIVE: We developed a custom-made miniaturized neural stimulation system with a liquid crystal polymer (LCP)-based electrode array for animal experiments. In order to verify the feasibility of the system, motor cortex stimulation (MCS) was applied on the rat pain model induced by sciatic nerve injury. MATERIALS AND METHODS: LCP is mechanically stable and chemically inert and has a much lower water absorption rate than other biocompatible polymers such as polyimide or parylene. In the present study, a film-type LCP substrate is used to microfabricate the cortical stimulation electrode array. A miniaturized electrical neuromodulation system is implemented using an application-specific integrated chip for generation of electrical stimulation current. In vivo experiment was performed using a rat neuropathic pain model induced by sciatic nerve injury. The electrodes were attached to the contralateral primary motor cortex, which processes the hind limb movement. Mechanical allodynia was measured before, during, and after electrical stimulation to determine the effects on pain threshold. RESULTS: Electrical stimulation into the brain structure processing pain perception was effective in alleviating neuropathic pain. The pain threshold of the rats increased more than fivefold during the electrical stimulation. CONCLUSION: We developed a miniaturized electrical stimulation system with a novel flexible LCP electrode array for MCS in rats. This system is expected to be used in studying various neurological diseases and examining in vivo brain function.

Beta-Barrel Nanopores as Diagnostic Sensors: An Engineering Perspective.

Biological nanopores are ultrasensitive and highly attractive platforms for disease diagnostics, including the sequencing of viral and microbial genes and the detection of biomarkers and pathogens. To utilize biological nanopores as diagnostic sensors, they have been engineered through various methods resulting in the accurate and highly sensitive detection of biomarkers and disease-related biomolecules. Among diverse biological nanopores, the ß-barrel-containing nanopores have advantages in nanopore engineering because of their robust structure, making them well-suited for modifications. In this review, we highlight the engineering approaches for ß-barrel-containing nanopores used in single-molecule sensing for applications in early diagnosis and prognosis. In the highlighted studies, ß-barrel nanopores can be modified by genetic mutation to change the structure; alter charge distributions; or add enzymes, aptamers, and protein probes to enhance sensitivity and accuracy. Furthermore, this review discusses challenges and future perspectives for advancing nanopore-based diagnostic sensors.

Liking Predicts Judgments of Authenticity in Real-Time Interactions More Robustly Than Personality States or Affect.

We conducted three studies involving small group interactions (N = 622) that examined whether Big Five personality states, affect, and/or liking predict judgments of others' authenticity. Study 1 (n = 119) revealed that neither self-rated personality states nor affect predicted other-rated authenticity. Instead, other-rated liking was the only predictor of other-rated authenticity. Study 2 (n = 281) revealed that other-rated personality states and affect were significant predictors of other-rated authenticity, but other-rated liking was a more important factor in predicting other-rated authenticity than specific behaviors or affect. Based on these results, Study 3 (n = 222) examined whether experimental manipulation of likability had a causal effect on other-ratings of authenticity. Likable actors were indeed judged as more authentic. Together, this suggests that we judge people we like as more authentic and that likability may be more important than the "objective" content of behavior.

Ventral posterolateral deep brain stimulation treatment for neuropathic pain shortens pain response after cold stimuli.

Neuropathic pain is often severe. Deep brain stimulation (DBS) is a treatment method for neuropathic pain, but its mechanism of action remains unclear. Patients with neuropathic pain are affected by various stimulations, such as mechanical and cold stimuli, but studies of cold allodynia showed the associated pain to be less than that caused by mechanical stimuli. This study focused on the effects of DBS on cold allodynia in rats. To observe the effects of DBS, we established three groups: a normal group (normal), a neuropathic pain group (pain), and a DBS with neuropathic pain group (DBS). The stimulation target was the ventral posterolateral nucleus (VPL). We observed differences in the degree of cold allodynia elicited between a conventional method that measured the number of pain responses and our altered novel method that measured the duration of pain responses. Cold allodynia after DBS did not differ when conventional analysis was applied, but the pain response duration was decreased. We suggest that VPL DBS was partially effective in cold allodynia, implicating complex pathways of pain signaling.

Neuronal Responses in the Globus Pallidus during Subthalamic Nucleus Electrical Stimulation in Normal and Parkinson's Disease Model Rats.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been widely used as a treatment for the movement disturbances caused by Parkinson's disease (PD). Despite successful application of DBS, its mechanism of therapeutic effect is not clearly understood. Because PD results from the degeneration of dopamine neurons that affect the basal ganglia (BG) network, investigation of neuronal responses of BG neurons during STN DBS can provide informative insights for the understanding of the mechanism of therapeutic effect. However, it is difficult to observe neuronal activity during DBS because of large stimulation artifacts. Here, we report the observation of neuronal activities of the globus pallidus (GP) in normal and PD model rats during electrical stimulation of the STN. A custom artifact removal technique was devised to enable monitoring of neural activity during stimulation. We investigated how GP neurons responded to STN stimulation at various stimulation frequencies (10, 50, 90 and 130 Hz). It was observed that activities of GP neurons were modulated by stimulation frequency of the STN and significantly inhibited by high frequency stimulation above 50 Hz. These findings suggest that GP neuronal activity is effectively modulated by STN stimulation and strongly dependent on the frequency of stimulation.

Implicit Theories of Happiness: When Happiness Is Viewed as Changeable, Happy People Are Perceived Much More Positively Than Unhappy People.

Happy people are often perceived positively, perhaps more than they actually are, whereas unhappy people are often perceived negatively, perhaps more than they actually are. What would make this bias stronger or weaker? The present research addresses this question by exploring the roles of implicit theories of happiness in the trait perceptions toward happy and unhappy people. Specifically, four studies (N = 998) tested hypotheses that an incremental theory of happiness would enhance and an entity theory of happiness would attenuate the trait perceptions favoring happy over unhappy people. Results found converging evidence that believing happiness as changeable (incremental theory) enhances the positive perceptions toward happy people, while providing less consistent evidence that believing happiness as fixed (entity theory) mitigates the negative perceptions toward unhappy people. The current research contributes to the literature on essentialism and advances the understanding of the roles of implicit theories of happiness in person perception.

VPL-DBS on neuropathic pain rat model is effective in mechanical allodynia than cold allodynia.

Recently, deep brain stimulation (DBS) is widely used in various types of neurodegenerative disorders for minimal invasiveness and safety of the procedure. Deep brain stimulation is consistently applied for the treatment of patients with neuropathic pain even though the success rate is not as high as other neurodegenerative disorders. Furthermore, it is also unclear how DBS improves neuropathic pain. In this study, we investigated the role of DBS following the stimulation parameter for analgesic effect on mechanical allodynia and cold allodynia in neuropathic pain rats. We used a sciatic nerve injury model to induce neuropathic pain, and observed responses to mechanical and cold stimulation by the von Frey test and acetone test, respectively. We classified the rats into four groups: naïve (naïve, n = 10), naïve + DBS (N + DBS, n = 10), neuropathic pain (NP, n = 10), and neuropathic pain + DBS (NP + DBS, n = 10). We inserted the DBS electrode into the ventral posterolateral nucleus (VPL) into the rats (VPL-DBS). The score for mechanical allodynia was significantly decreased in NP + DBS group (p < 0.01). However, the score for cold allodynia did not significantly drop in any groups including NP + DBS group (p > 0.05). In this study, we found that the electrical stimulation of the VPL works more effectively with mechanical allodynia than cold one, and pain signal induced by mechanical stimulus and cold stimulus may be processed through different pathways in the brain.

Longitudinal examinations of changes in well-being during the early period of the COVID-19 pandemic: Testing the roles of extraversion and social distancing.

The present research, by using longitudinal data collected in South Korea (N = 69,986) during the early period of the COVID-19 pandemic (1 January-7 April 2020), examined the pandemic-related changes in the relationship between extraversion and well-being. Multilevel analyses revealed that participants experienced decreased well-being during the pandemic. When analyzing the responses (n = 3,229) completed during all the periods encompassing the COVID-19-related events (e.g., outbreak of COVID-19), we found the greater within-person decreases in well-being among extraverts than introverts after the intensive social distancing. This finding suggests that social distancing, as a necessary means to curb the spread of COVID-19, inadvertently reduced well-being of extraverts. Implications for the person-environment fit literature, limitations, and future research avenues are discussed.

Experiential appreciation as a pathway to meaning in life.

A key research program within the meaning in life (MIL) literature aims to identify the key contributors to MIL. The experience of existential mattering, purpose in life and a sense of coherence are currently posited as three primary contributors to MIL. However, it is unclear whether they encompass all information people consider when judging MIL. Based on the ideas of classic and contemporary MIL scholars, the current research examines whether valuing one's life experiences, or experiential appreciation, constitutes another unique contributor to MIL. Across seven studies, we find support for the idea that experiential appreciation uniquely predicts subjective judgements of MIL, even after accounting for the contribution of mattering, purpose and coherence to these types of evaluations. Overall, these findings support the hypothesis that valuing one's experiences is uniquely tied to perceptions of meaning. Implications for the incorporation of experiential appreciation as a fundamental antecedent of MIL are discussed.

Morphometric analysis of the anterior region of the maxillary bone for immediate implant placement using micro-CT.

The purpose of this study was to elucidate the relationship between the maxillary incisor roots and surrounding alveolar structures using microscopic computerized tomography (micro-CT) for the immediate implant placement. Nineteen maxillae from 14 Korean cadavers were used in this study. All specimens were scanned and reconstructed into a three-dimensional (3D) structure using a micro-CT system. The roots of the maxillary central and lateral incisors became dramatically narrower from 6 mm above the cementoenamel junctions to the apex. The roots of the maxillary incisors and canine were located at the labial one fifths region of the alveolar bone. The angle formed by the longitudinal root axis and the alveolar bone was greatest at the maxillary canine. On the basis of the results of this study, guidelines for immediate implant placement can be suggested on the implant diameter and drilling angle to minimize damage of the alveolar plate.