Transfer of visual perceptual learning over a task-irrelevant feature through feature-invariant representations: Behavioral experiments and model simulations.

A large body of literature has examined specificity and transfer of perceptual learning, suggesting a complex picture. Here, we distinguish between transfer over variations in a "task-relevant" feature (e.g., transfer of a learned orientation task to a different reference orientation) and transfer over a "task-irrelevant" feature (e.g., transfer of a learned orientation task to a different retinal location or different spatial frequency), and we focus on the mechanism for the latter. Experimentally, we assessed whether learning a judgment of one feature (such as orientation) using one value of an irrelevant feature (e.g., spatial frequency) transfers to another value of the irrelevant feature. Experiment 1 examined whether learning in eight-alternative orientation identification with one or multiple spatial frequencies transfers to stimuli at five different spatial frequencies. Experiment 2 paralleled Experiment 1, examining whether learning in eight-alternative spatial-frequency identification at one or multiple orientations transfers to stimuli with five different orientations. Training the orientation task with a single spatial frequency transferred widely to all other spatial frequencies, with a tendency to specificity when training with the highest spatial frequency. Training the spatial frequency task fully transferred across all orientations. Computationally, we extended the identification integrated reweighting theory (I-IRT) to account for the transfer data (Dosher, Liu, & Lu, 2023; Liu, Dosher, & Lu, 2023). Just as location-invariant representations in the original IRT explain transfer over retinal locations, incorporating feature-invariant representations effectively accounted for the observed transfer. Taken together, we suggest that feature-invariant representations can account for transfer of learning over a "task-irrelevant" feature.

Enabling identification of component processes in perceptual learning with nonparametric hierarchical Bayesian modeling.

Perceptual learning is a multifaceted process, encompassing general learning, between-session forgetting or consolidation, and within-session fast relearning and deterioration. The learning curve constructed from threshold estimates in blocks or sessions, based on tens or hundreds of trials, may obscure component processes; high temporal resolution is necessary. We developed two nonparametric inference procedures: a Bayesian inference procedure (BIP) to estimate the posterior distribution of contrast threshold in each learning block for each learner independently and a hierarchical Bayesian model (HBM) that computes the joint posterior distribution of contrast threshold across all learning blocks at the population, subject, and test levels via the covariance of contrast thresholds across blocks. We applied the procedures to the data from two studies that investigated the interaction between feedback and training accuracy in Gabor orientation identification over 1920 trials across six sessions and estimated learning curve with block sizes L = 10, 20, 40, 80, 160, and 320 trials. The HBM generated significantly better fits to the data, smaller standard deviations, and more precise estimates, compared to the BIP across all block sizes. In addition, the HBM generated unbiased estimates, whereas the BIP only generated unbiased estimates with large block sizes but exhibited increased bias with small block sizes. With L = 10, 20, and 40, we were able to consistently identify general learning, between-session forgetting, and rapid relearning and adaptation within sessions. The nonparametric HBM provides a general framework for fine-grained assessment of the learning curve and enables identification of component processes in perceptual learning.

Esterase-Responsive Polymeric Micelles Containing Tetraphenylethene and Poly(ethylene glycol) Moieties for Efficient Doxorubicin Delivery and Tumor Therapy.

Enzyme-responsive drug delivery systems have drawn much attention in the field of cancer theranostics due to their high sensitivity and substrate specificity under mild conditions. In this study, an amphiphilic polymer T1 is reported, which contains a tetraphenylethene unit and a poly(ethylene glycol) chain linked by an esterase-responsive phenolic ester bond. In aqueous solution, T1 formed stable micelles via self-assembly, which showed an aggregation-induced emission enhancement of 32-fold at 532 nm and a critical micelle concentration of 0.53 µM as well as esterase-responsive activity. The hydrophobic drug doxorubicin (DOX) was efficiently encapsulated into the micelles with a drug loading of 21%. In the presence of the esterase, the selective decomposition of drug-loaded T1 micelles was observed, and DOX was subsequently released with a half-life of 5 h. In vitro antitumor studies showed that T1@DOX micelles exhibited good therapeutic effects on HeLa cells, while normal cells remained mostly intact. In vivo anticancer experiments revealed that T1@DOX micelles indeed suppressed tumor growth and had reduced side effects compared to DOX·HCl. The present work showed the potential clinical application of esterase-responsive drug delivery in cancer therapy.

A novel quick contrast sensitivity function test in Chinese adults with myopia and its related parameters.

PURPOSE: This study is to investigate the contrast sensitivity function (CSF) using the quick CSF (qCSF) test in Chinese adults with myopia. METHODS: This case series study included 320 myopic eyes of 160 patients (mean age 27.75 ± 5.99 years) who underwent a qCSF test for acuity, area under log CSF (AULCSF), and mean contrast sensitivity (CS) at 1.0, 1.5, 3.0, 6.0, 12.0, and 18.0 cycle per degree (cpd). Spherical equivalent, corrected-distant visual acuity (CDVA), and pupil size were recorded. RESULTS: The spherical equivalent, CDVA (LogMAR), spherical refraction, cylindrical refraction, and the scotopic pupil size of the included eyes were - 6.30 ± 2.27 D (- 14.25 to - 0.88 D), 0 ± 0.02, - 5.74 ± 2.18 D, - 1.11 ± 0.86 D, and 6.77 ± 0.73 mm, respectively. The AULCSF and CSF acuity were 1.01 ± 0.21 and 18.45 ± 5.39 cpd, respectively. The mean CS (log units) at six different spatial frequencies were 1.25 ± 0.14, 1.29 ± 0.14, 1.25 ± 0.14, 0.98 ± 0.26, 0.45 ± 0.28, and 0.13 ± 0.17, respectively. A mixed effect model showed significant correlations between age and acuity, AULCSF, and CSF at 1.0, 12.0, and 18.0 cpd. Interocular CSF differences were correlated with the interocular difference of spherical equivalent, spherical refraction (at 1.0 cpd, 1.5 cpd), and cylindrical refraction (at 12.0 cpd, 18.0 cpd). The lower cylindrical refraction eye had higher CSF compared with the higher cylindrical refraction eye (0.48 ± 0.29 vs. 0.42 ± 0.27 at 12.0 cpd and 0.15 ± 0.19 vs. 0.12 ± 0.15 at 18.0 cpd). CONCLUSIONS: The age-related decrease in contrast sensitivity is at low and high spatial frequencies. Higher-degree myopia may show a decrease in CSF acuity. Low astigmatism was noted to affect the contrast sensitivity significantly.

General learning ability in perceptual learning.

Developing expertise in any field usually requires acquisition of a wide range of skills. Most current studies on perceptual learning have focused on a single task and concluded that learning is quite specific to the trained task, and the ubiquitous individual differences reflect random fluctuations across subjects. Whether there exists a general learning ability that determines individual learning performance across multiple tasks remains largely unknown. In a large-scale perceptual learning study with a wide range of training tasks, we found that initial performance, task, and individual differences all contributed significantly to the learning rates across the tasks. Most importantly, we were able to extract both a task-specific but subject-invariant component of learning, that accounted for 38.6% of the variance, and a subject-specific but task-invariant perceptual learning ability, that accounted for 36.8% of the variance. The existence of a general perceptual learning ability across multiple tasks suggests that individual differences in perceptual learning are not "noise"; rather, they reflect the variability of learning ability across individuals. These results could have important implications for selecting potential trainees in occupations that require perceptual expertise and designing better training protocols to improve the efficiency of clinical rehabilitation.

Characteristics and Related Parameters of Quick Contrast Sensitivity Function in Chinese Ametropia Children.

PURPOSE: To investigate the characteristics of quick contrast sensitivity function (qCSF) and its related parameters in Chinese ametropia children. METHODS: This case series study enrolled 106 eyes of 53 children (male/female=29/24, age: 9.04±2.06 years). Examinations included manifest refraction, axial length, corneal curvature, and monocular and binocular qCSF readings without refractive correction (area under log CSF [AULCSF], CSF acuity, and contrast sensitivity [CS] at 1.0 to 18.0 cpd). The subjects were divided into groups according to age and refractive parameters for analysis. RESULTS: The mean spherical equivalent (SE), AULCSF, and CSF acuity of the test eyes were -0.94±1.53 D, 0.44±0.33, and 8.50±5.97 cpd, respectively. In the monocular qCSF comparison, the refraction sphere (RS) was the major factor correlated with qCSF readings (B=0.186, P =0.009 for AULCSF; B=0.543, P =0.019 for CSF acuity; generalized linear model). The three groups stratified by RS/SE (<-1.00D, -1.00D to 0D, and >0D) showed significant differences in CS at medium spatial frequencies (3.0 and 6.0 cpd; all P <0.05). In the low RS/SE group (within -1 to 0 D), the CS at 12.0 cpd was significantly lower than that in the hyperopia group (all P <0.05). Binocular qCSF readings were significantly correlated with those of the eyes with lower RS (all P <0.05). CONCLUSION: RS and SE are the major contributing factors of qCSF without refractive correction in children. The CS at medium spatial frequencies decrease significantly as the RS/SE increase. In low myopia children, the CS at medium and high spatial frequencies are significantly decreased, providing practical value in visual function screening in children.

Hierarchical Bayesian perceptual template modeling of mechanisms of spatial attention in central and peripheral cuing.

The external noise paradigm and perceptual template model (PTM) have successfully been applied to characterize observer properties and mechanisms of observer state changes (e.g. attention and perceptual learning) in several research domains, focusing on individual level analysis. In this study, we developed a new hierarchical Bayesian perceptual template model (HBPTM) to model the trial-by-trial data from all individuals and conditions in a published spatial cuing study within a single structure and compared its performance to that of a Bayesian Inference Procedure (BIP), which separately infers the posterior distributions of the model parameters for each individual subject without the hierarchical structure. The HBPTM allowed us to compute the joint posterior distribution of the hyperparameters and parameters at the population, observer, and experiment levels and make statistical inferences at all these levels. In addition, we ran a large simulation study that varied the number of observers and number of trials in each condition and demonstrated the advantage of the HBPTM over the BIP across all the simulated datasets. Although it is developed in the context of spatial attention, the HBPTM and its extensions can be used to model data from the external noise paradigm in other domains and enable predictions of human performance at both the population and individual levels.

Learning spatial frequency identification through reweighted decoding.

Perceptual learning, the improvement of perceptual judgments with practice, occurs in many visual tasks. There are, however, relatively fewer studies examining perceptual learning in spatial frequency judgments. In addition, perceptual learning has generally been studied in two-alternative tasks, occasionally in n-alternative tasks, and infrequently in identification. Recently, perceptual learning was found in an orientation identification task (eight-alternatives) and was well accounted for by a new identification integrated reweighting theory (I-IRT) (Liu et al., submitted). Here, we examined perceptual learning in a similar eight-alternative spatial frequency absolute identification task in two different training protocols, finding learning in the majority but not all observers. We fit the I-IRT to the spatial frequency learning data and discuss possible model explanations for variations in learning.

Collective endpoint of visual acuity and contrast sensitivity function from hierarchical Bayesian joint modeling.

Clinical trials typically analyze multiple endpoints for signals of efficacy. To improve signal detection for treatment effects using the high-dimensional data collected in trials, we developed a hierarchical Bayesian joint model (HBJM) to compute a five-dimensional collective endpoint (CE5D) of contrast sensitivity function (CSF) and visual acuity (VA). The HBJM analyzes row-by-row CSF and VA data across multiple conditions, and describes visual functions across a hierarchy of population, individuals, and tests. It generates joint posterior distributions of CE5D that combines CSF (peak gain, peak frequency, and bandwidth) and VA (threshold and range) parameters. The HBJM was applied to an existing dataset of 14 eyes, each tested with the quantitative VA and quantitative CSF procedures in four Bangerter foil conditions. The HBJM recovered strong correlations among CE5D components at all levels. With 15 qVA and 25 qCSF rows, it reduced the variance of the estimated components by 72% on average. Combining signals from VA and CSF and reducing noises, CE5D exhibited significantly higher sensitivity and accuracy in discriminating performance differences between foil conditions at both the group and test levels than the original tests. The HBJM extracts valuable information about covariance of CSF and VA parameters, improves precision of the estimated parameters, and increases the statistical power in detecting vision changes. By combining signals and reducing noise from multiple tests for detecting vision changes, the HBJM framework exhibits potential to increase statistical power for combining multi-modality data in ophthalmic trials.

Covalently Linked Hexakis(m-Phenylene Ethynylene) Macrocycles as Molecular Nanotubes.

The construction of nanotubular structures with non-deformable inner pores is of both fundamental and practical significance. Herein we report a strategy for creating molecular nanotubes with defined lengths. Macrocyclic (MC) units based on shape-persistent hexakis(m-phenylene ethynylene) (m-PE) macrocycle MC-1, which are known to stack into hydrogen-bonded tubular assemblies, are tethered by oligo(ß-alanine) linkers to give tubular stacks MC-2 and MC-4 that have two and four MC units, respectively. The covalently linked MC units in MC-2 and MC-4 undergo face-to-face stacking through intramolecular non-covalent interactions that further results in the helical stacks of these compounds. Oligomer MC-4 can form potassium and proton channels across lipid bilayers, with the channels being open continuously for over 60 seconds, which is among the longest open durations for synthetic ion channels and indicates that the thermodynamic stability of the self-assembling channels can be drastically enhanced by reducing the number of molecular components involved. This study demonstrates that covalently tethering shape-persistent macrocyclic units is a feasible and reliable approach for building molecular nanotubes that otherwise are difficult to create de novo. The extraordinarily long lifetimes of the ion channels formed by MC-2 and MC-4 suggest the likelihood of constructing the next-generation synthetic ion channels with unprecedented stability.

A NIR Aggregation-Induced Emission Fluoroamphiphile as Visually Trackable and Serum-Tolerant Nonviral Gene Carrier.

Functional fluorescence (FL) nonviral gene vectors with high serum tolerance bear broad application prospects in gene delivery. Fluorination has been widely utilized as an effective strategy to enhance serum tolerance. Herein, we show the combination of fluorination and aggregation-induced emission (AIE) for the construction of a nonviral gene vector with low cytotoxicity, visual tracking ability, and high serum tolerance. Large π-conjugation triphenylamine (TPA) derivative with a characteristic D-π-A structure was modified with two polar [12]aneN3 heads and a long fluorocarbon tail, giving the vector molecule FluoTPA. FluoTPA features near-infrared (NIR) emission, large Stokes shift, and strong binding affinity toward nucleic acids. Liposomes consisting of FluoTPA and dioleoylphosphatidylethanolamine (DOPE) (FluoTPA/DOPE) can effectively deliver both plasmid DNAs (pDNAs) and siRNAs into cells. Impressively, FluoTPA/DOPE showed comparable transfection efficiency (TE) in the presence of serum content up to 30% with that in the serum-free condition and achieved 7.4 times higher TE than the commercial transfection agent lipofectamine 2000 at the same condition. Finally, spatiotemporal tracking of the delivery process in cells was demonstrated. The results in this work suggest that FluoTPA could be a reliable theranostic platform for the nonviral delivery of nucleic acid therapeutics in serum condition.

Identifying Long- and Short-Term Processes in Perceptual Learning.

Practice makes perfect in almost all perceptual tasks, but how perceptual improvements accumulate remains unknown. Here, we developed a multicomponent theoretical framework to model contributions of both long- and short-term processes in perceptual learning. Applications of the framework to the block-by-block learning curves of 49 adult participants in seven perceptual tasks identified ubiquitous long-term general learning and within-session relearning in most tasks. More importantly, we also found between-session forgetting in the vernier-offset discrimination, face-view discrimination, and auditory-frequency discrimination tasks; between-session off-line gain in the visual shape search task; and within-session adaptation and both between-session forgetting and off-line gain in the contrast detection task. The main results of the vernier-offset discrimination and visual shape search tasks were replicated in a new experiment. The multicomponent model provides a theoretical framework to identify component processes in perceptual learning and a potential tool to optimize learning in normal and clinical populations.

Topology-preserving smoothing of retinotopic maps.

Retinotopic mapping, i.e., the mapping between visual inputs on the retina and neuronal activations in cortical visual areas, is one of the central topics in visual neuroscience. For human observers, the mapping is obtained by analyzing functional magnetic resonance imaging (fMRI) signals of cortical responses to slowly moving visual stimuli on the retina. Although it is well known from neurophysiology that the mapping is topological (i.e., the topology of neighborhood connectivity is preserved) within each visual area, retinotopic maps derived from the state-of-the-art methods are often not topological because of the low signal-to-noise ratio and spatial resolution of fMRI. The violation of topological condition is most severe in cortical regions corresponding to the neighborhood of the fovea (e.g., < 1 degree eccentricity in the Human Connectome Project (HCP) dataset), significantly impeding accurate analysis of retinotopic maps. This study aims to directly model the topological condition and generate topology-preserving and smooth retinotopic maps. Specifically, we adopted the Beltrami coefficient, a metric of quasiconformal mapping, to define the topological condition, developed a mathematical model to quantify topological smoothing as a constrained optimization problem, and elaborated an efficient numerical method to solve the problem. The method was then applied to V1, V2, and V3 simultaneously in the HCP dataset. Experiments with both simulated and real retinotopy data demonstrated that the proposed method could generate topological and smooth retinotopic maps.

H2O2-Responsive amphiphilic polymer with aggregation-induced emission (AIE) for DOX delivery and tumor therapy.

Stimuli-responsive drug delivery systems (DDSs) based on amphiphilic polymers have attracted much attention. In this study, we reported an innovative H2O2-responsive amphiphilic polymer (TBP), bearing a H2O2-sensitive phenylboronic ester, AIE fluorophore tetraphenylethene (TPE) hydrophobic, and polyethylene glycol hydrophilic (PEG) moieties. TBP could self-assemble into micelles with an encapsulation efficiency as high as 74.9% for doxorubicin (DOX) in aqueous solution. In the presence of H2O2, TBP micelles was decomposed by oxidation, hydrolysis and rearrangement, leading to almost 80% DOX release from TBP@DOX micelles. TBP and the corresponding degradation products were biocompatible, while TBP@DOX micelles only displayed obvious toxicity toward cancer cells. Drug delivery process was clearly monitored by confocal laser scanning microscopic (CLSM) and flow cytometry (FCM) analysis. Moreover, in vivo anticancer study showed that TBP@DOX micelles were accumulated in tumor region of nude mice and effectively inhibited tumor growth. The results suggested that the reported H2O2-responsive amphiphilic polymer displayed great potential in drug delivery and tumor therapy.

Quantification of Myelinated Nerve Fraction and Degeneration in Spinal Cord Neuropil by SHIFT MRI.

BACKGROUND: Neurodegeneration is a complex cellular process linked to prompt changes in myelin integrity and gradual neuron loss. Current imaging techniques offer estimations of myelin volumes in lesions/remyelinated areas but are limited to detect subtle injury. PURPOSE: To investigate whether measurements detected by a signal hierarchically isolated as a function of time-to-echo (SHIFT) MRI technique can determine changes in myelin integrity and fiber axolemma. STUDY TYPE: Prospective animal model. ANIMAL MODEL: Surgically demyelinated spinal cord (SC) injury model in rodents (n = 6). FIELD STRENGTH/SEQUENCE: Gradient-echo spin-echo at 3T. ASSESSMENT: Multicompartment T2 relaxations were computed by SHIFT MRI in 75-microns-resolution images of the SC injury penumbra region 2 weeks post-trauma. G-ratio and axolemma delamination were assessed by transmission electron microscopy (TEM) in intact and injured samples. SC myelinated nerve fraction was computed by SHIFT MRI prospectively and assessed histologically. STATISTICAL TESTS: Relations between SHIFT-isolated T2 -components and TEM measurements were studied using linear regression and t-tests. Pearson's correlation and significance were computed to determine the SHIFT's sensitivity to detect myelinated fibers ratio in gray matter. Regularized least-squares-based ranking analysis was employed to determine SHIFT MRI's ability to discern intact and injured myelinated nerves. RESULTS: Biexponential signals isolated by SHIFT MRI for intact vs. lesion penumbra exhibited changes in T2 , shifting from intermediate components (25 ± 2 msec) to long (43 ± 11 msec) in white matter, and similarly in gray matter regions-of-interest (31 ± 2 to 46 ± 16 msec). These changes correlated highly with TEM g-ratio and axon delamination measurements (P < 0.05). Changes in short T2 components were observed but not statistically significant (8.5 ± 0.5 to 7 ± 3 msec, P = 0.445, and 4.0 ± 0.9 to 7 ± 3 msec, P = 0.075, respectively). SHIFT MRI's ability to detect myelinated fibers within gray matter was confirmed (P < 0.001). DATA CONCLUSION: Changes detected by SHIFT MRI are associated with abnormal intermembrane spaces formed upon mild injury, directly correlated with early neuro integrity loss. Level of Evidence 1 Technical Efficacy Stage 2.

An unnatural tripeptide structure containing intramolecular double H-bonds mimics a turn hairpin conformation.

A series of unnatural tripeptides, each consisting of two aromatic γ-amino acid residues and an ϖ-amino acid residue, are designed to probe their folding into hairpin conformations. The ϖ-amino acid residues, with aliphatic or aromatic spacers of different sizes, serve as the loop of the hairpins. Studies based on one-dimensional (1D) 1H NMR performed at different concentrations, solvent polarity, and temperature, along with 2D-NMR studies, demonstrated that the doubly H-bonded aromatic γ-amino acid residues play important roles in driving these tripeptides into the hairpin conformation. The loop based on 5-aminovaleric acid, which offers a four-carbon (CH2)4 spacer, enhanced the stability of the corresponding hairpin, while loops having a shorter, a longer and a more rigid spacer disfavored the formation of the hairpins. Results from computational studies are in good agreement with the experimental observations. Furthermore, the crystal structure of peptide 1b revealed the expected hairpin conformation in the solid state. This turn motif, which contains H-bonded aromatic γ-amino acid residues as the core unit and an ϖ-amino acid residue serving as the loop, provides a new platform that can be used to obtain a variety of turn conformations by incorporating diverse amino acids into the loops.

Degradable cationic polyesters via ring-opening copolymerization of valerolactones as nanocarriers for the gene delivery.

The development of cationic polymers as non-viral gene vectors has been hurdled by their high toxicity, thus degradable and biocompatible polymers are urgently demanded. Herein, five polyesters (B3a-B3e) were synthesized based on the ring-opening copolymerization between α-allyl-δ-valerolactone and δ-valerolactone derivatives decorated with alkyl or alkoxyl chains of different lengths, followed by the modification with 1,5,9-triazacyclododecyl ([12]aneN3) through thiol-ene click reactions. The five polyesters effectively condensed DNA into nanoparticles. Of them, B3a with a shorter alkyl chain and B3d with more positive charged units showed stronger DNA condensing performance and can completely retard the migration of DNA at N/P = 1.6 in the presence of DOPE. B3b/DOPE with a longer alkyl chain exhibited the highest transfection efficiency in HeLa cells with 1.8 times of 25 kDa PEI, while B3d/DOPE with more positive charged units exhibited highest transfection efficiency in A549 cells with 2.3 times of 25 kDa PEI. B3b/DOPE and B3d/DOPE successfully delivered pEGFP into zebrafish, which was superior to 25 kDa PEI (1.5 folds and 1.1 folds, respectively). The cytotoxicity measurements proved that the biocompatibility of these polyesters was better than 25 kDa PEI, due to their degradable property in acid environment. The results indicated that these cationic polyesters can be developed as potential non-viral gene vectors for DNA delivery.

Integration of [12]aneN3 and Acenaphtho[1,2-b]quinoxaline as non-viral gene vectors with two-photon property for enhanced DNA/siRNA delivery and bioimaging.

Two-photon fluorescent Acenaphtho[1,2-b]quinoxaline (ANQ) and the hydrophilic di-(triazole-[12]aneN3) moieties were combined through an alkyl chain (ANQ-A-M) or a ß-hairpin motif with two aromatic γ-amino acid residues (ANQ-H-M) to explore their capabilities for in vitro and in vivo gene delivery and tracing. ANQ-A-M and ANQ-H-M showed the same maximum absorption at 420 nm, and their fluorescent intensities around 650 nm were varied in different solvents and became poor in the protic solvents. Gel electrophoresis assays indicated that both compounds completely retarded the migration of pDNA at 20 µM in the presence of DOPE. However, the DNA condensation with ANQ-H-M was not reversible, and the particle size of the corresponding complexes were larger indicated from the SEM and DLS measurements. In vitro transfections indicated ANQ-A-M/DOPE achieved Luciferase and GFP expressions were to be 7.9- and 5.7-fold of those by Lipo2000 in A549 cells respectively. However, ANQ-H-M showed very poor transfection efficiency in Luciferase expression. With the help of single/two-photon fluorescence imaging it clearly demonstrated that the successful transfection of ANQ-A-M was attributed to its cellular uptake, apparent lysosomal escape, and reversible release of DNA; and the poor transfection of ANQ-H-M was resulted from the aggregation of the DNA complexes which prevented them from the cellular uptake, and also the strong binding ability which is not easy to release DNA. ANQ-A-M/DOPE also exhibited robust gene silencing (83% knockdown of Luciferase) and GFP expression (2.47-fold higher) efficiency compared with Lipo2000 in A549 and zebrafish, respectively. The work demonstrated that the linkage structure between fluorescent and di(triazole-[12]aneN3) played the important role for their gene delivery performance, and that ANQ-A-M represents a vector with the strong transfection efficiency in vitro and in vivo as well as the efficient real time bioimaging properties, which is potential for the development in biomedical research.

Association of Self-Paced Physical and Cognitive Activities Across the First Week Postconcussion With Symptom Resolution in Youth.

OBJECTIVE: To examine the association of objectively measured, self-paced physical and cognitive activities across the first week postconcussion with symptom resolution in youth. SETTING: Emergency department or concussion clinics. PARTICIPANTS: Youth aged 11 to 17 years with physician-confirmed concussion. DESIGN: Prospective cohort with repeated measures. MAIN MEASURES: Days from injury to symptom resolution, based on daily ratings by youth on the Post-Concussive Symptom Scale. Physical and cognitive activities were assessed using an ActiGraph and a Narrative Clip, respectively. RESULTS: A total of 83 youth participants were included (n = 54 [65%] males; mean age = 14.2 years, SD = 1.9). While self-paced daily physical and cognitive activities increased across the first week postinjury, daily postconcussion symptoms decreased. Increased daily step count was associated with an increased likelihood of early symptom resolution (hazard ratio [HR] = 1.17; 95% confidence interval [CI], 1.02-1.34). However, this association was not statistically significant after adjusting for acute postconcussion symptoms and other covariates. Greater school attendance time was associated with earlier symptom resolution (adjusted HR = 1.14; 95% CI, 1.02-1.27). CONCLUSION: Self-paced physical and cognitive activities across the first week postinjury alone neither hastened nor prolonged concussion recovery. Youth with concussion may have some latitude to determine their activity levels.

Test-retest Reliability of the qReading Method in Normally Sighted Young Adults.

SIGNIFICANCE: We recently developed a novel Bayesian adaptive method, qReading, to measure reading function. The qReading method has both the efficiency and excellent test-retest reliability in normally sighted young adults to make it an excellent candidate for future studies of its value in diagnosis and longitudinal evaluation of treatment and/or rehabilitation outcomes. PURPOSE: A novel Bayesian adaptive method, qReading, was recently developed to measure reading function. Here we performed a systematic assessment of the test-retest reliability of the qReading method. METHODS: The variability of five repeated measurements of the reading curve was examined in two settings: within session and between sessions. For the within-session design, we considered two subpopulations: naive observers and experienced observers. All observers were normally sighted young adults. For each set of data, in addition to examining the intrinsic precision of the qReading method (the half width of the credible interval of the posterior distribution of the estimated performance), we computed four metrics to assess repeatability: standard deviation, Bland-Altman coefficient of repeatability, correlation coefficient, and Fractional Rank Precision. RESULTS: Extrinsic factors such as observer, time interval between repeated measures, and observer experience all contribute to the variation across measurements. Nevertheless, the four metrics consistently show that the variability across five repeated measurements is small for each set of data. This is true even without taking learning effects into account (standard deviations, ≤0.092 log10 units; Bland-Altman coefficient of repeatability, ≤0.15 (log10)2 units; correlation coefficient, ≥0.91; and Fractional Rank Precision, ≥0.81). CONCLUSIONS: The qReading method has excellent test-retest reliability in normally sighted young adults.