Results of the principal component regression (PCR) analysis.

(A) The regression coefficient (B) of the principal components predicts PoP. The three PCs are represented by dashed, dotted, and solid plots. Circle and triangle markers represent the significant reach distances (p(B) Factor loadings of PC2. (C) Factor loadings of PC3. The distances between two vertical dashed lines correspond to the distances found significant in regression. PC2 was positively loaded by TSDN and negatively by TNDR in the early phase (between vertical dashed lines in Fig 3B), both containing prior distractor color features. PC3 was positively loaded by TNDS and negatively by TRDN in the late phase (between vertical dashed lines in Fig 2C), containing prior target color features. See supplementary information for the factor loadings of PC1 and the eigenvalues (Figs A and B in S2 Text).</p

Principal component regression (PCR) analysis.

Fig A. Factor loadings of PC1. Fig B. The cumulative variance explained by the three PCs across reach distance. Fig C. An illustration of a typical reversal effect between TSDN (medium green) and TNDS (light green) in model 3b (facilitation precedes inhibition) with non-optimal parameters. (PDF)</p

An overview of SH-CoR architecture.

The model consists of two processes: Target Selection (left) and Movement Production (right). Each process comprises several modules (boxes with solid black lines). The Target Selection process consists of layers of model neurons (illustrated dotted lines, as circles C1, C2, C3, and C4 for four colors used in the experiment) in the modules, modeling the neuron-like responses to the four colors. The shading of the nodes illustrates the level of activation for the current trial, with white being the highest activation and black the lowest. Both processes and their modules operate parallel (analogous to brain regions), allowing SH-CoR to produce the leakage effect. The first stage of Target Selection (Color Processing module) determines color Feature Maps and the saliency of the colors present in the Color Display using different color units (Color Saliency Layer). For instance, in the above display, C1 (white circle) and C2 (gray) represent the most and least salient colors in the display, while C3 and C4 (black circles) represent colors absent in the display. Based on the output of the Color Saliency Layer (see S3.A and Eq. S1 in S3 Text), the Odd Color Selection module selects the most salient color. It identifies the distractor and absent colors via color competition (Eq. S2 in S3 Text). These feature units are assigned labels, T (target color), D (distractor color), and N (absent color). The line graphs above the units remind us that color competition is a temporal process (not instantaneous) whose speed is proportional to the color saliency. These temporal activations are combined with the output of the Feature Maps in a multiplicative way (Eq. S3 in S3 Text). Initially, all possible item locations compete to become the target location, but the color competition ensures that the salient item dominates the location competition. This way, the feature map of the winning color (odd-color) eventually dominates the input to a competition of locations, generating the Target Location Representation (Eq. S4 in S3 Text). In addition, the Target Selection is also influenced by the Selection History module. This process stores the target and distractor features from the previous trial (see dotted lines; Eq. S6 in S3 Text) in separate layers. The layers in the Selection History module, in turn, influence the selection of the current target through facilitation and/or inhibition mechanism depending on which of the five models of inter-trial selection history are implemented in a particular instantiation of SH-CoR (see the gray dialog box).</p

Simulation results and performance of SH-CoR modeling.

(A) Examples of the modeling displays and simulated reaching trajectories (black lines) in a single trial. Colored squares represent targets and distractors in each display. The display in the previous trial would have the same target and distractor colors as in TRDR. Here we only show the displays and the examples of reaching trajectories for each condition in the current trial. Note that the target is always positioned at the bottom-right corner of the display for a clear illustration. (B) The averaged attraction scores of twenty-one repetitions for each best-fitted model with the application of noise in the color selection process and the goodness-of-fit for the five models. The parameter settings of each model can be found in Table C in S3 Text. The model performance is presented as error measurements (Eq. S16-19 in S3 Text), with error bars indicating a standard error (Methods and S3.D-E in S3 Text for more details).</p

Schematic of the color-oddity task, sample reach trajectories, and behavioral results.

(A) Schematic display sequences for different types of experimental conditions. An odd-colored target is presented with three homogeneously colored distractors in the color-oddity task. Participants search for and reach toward the odd-colored target with their index fingers. The colors of the target and distractors are pseudo-randomly selected from a pool of four colors (red, green, blue, and purple). The target location is randomly selected from one of the four locations of the imaginary square. We plotted the subset of color feature combinations inside a color-coded frame with a condition label for the demonstration purpose only. Experimental conditions are created depending on whether both (full) or one of the two-color features (partial) from a previous trial (Trial n-1) reappeared in a current trial (Trial n) and whether the reappeared color feature served the repeated (R) or swapped (S) target/distractor role. Each condition is labeled to indicate whether the color of the current target (T) or distractor (D) is repeated (R), swapped (S), or new (N) concerning the previous trial. For instance, in the TRDN condition, while the color of the target is repeated from the previous one, that of distractors is new. In the TNDS condition, while the color of the target is new, that of distractors is swapped from a previous target color. (B) Examples of reach movement trajectories from one participant. Curved reach trajectories from the full swap (TSDS, dark green) condition are contrasted with direct movements from the full repeat condition (TRDR, dark red). (C) Attraction scores for all six experimental conditions. The positive value of the attraction score represents hand movement toward the distractors, whereas the negative value represents hand movement toward the target. The shaded region represents the within-subject standard error of the mean. Color codes are identical to Fig 1B.</p

Display the mean (SE) for behavioral performance in the color-oddity task for the six experimental conditions with one baseline condition.

Display the mean (SE) for behavioral performance in the color-oddity task for the six experimental conditions with one baseline condition.</p

Priming effect comparison.

Fig A. Results comparing full priming and partial priming effect. (PDF)</p

Computational Modelling.

Table A. Parameter setting for color saliencies. Table B. Best fitted model parameters for the Target Selection process. Table C. Parameter ranges of the final grid search in the Target Selection process for the five models. Table D. DNFs parameters in the Movement Production process. S3.A. Target Selection process and mathematical description. S3.B. Selection History module. S3.C. Movement Production process and mathematical description. S3.D. Searching for best parameters. S3.E. Goodness-of-fit. Eq.S1 –S19. (PDF)</p

Novel reverse electrodialysis-driven iontophoretic system for topical and transdermal delivery of poorly permeable therapeutic agents

<p>Topical and transdermal drug delivery has great potential in non-invasive and non-oral administration of poorly bioavailable therapeutic agents. However, due to the barrier function of the stratum corneum, the drugs that can be clinically feasible candidates for topical and transdermal delivery have been limited to small-sized lipophilic molecules. Previously, we fabricated a novel iontophoretic system using reverse electrodialysis (RED) technology (RED system). However, no study has demonstrated its utility in topical and/or transdermal delivery of poorly permeable therapeutic agents. In this study, we report the topical delivery of fluorescein isothiocyanate (FITC)–hyaluronic acid (FITC–HA) and vitamin C and the transdermal delivery of lopinavir using our newly developed RED system in the <i>in vitro</i> hairless mouse skin and <i>in vivo</i> Sprague–Dawley rat models. The RED system significantly enhanced the efficiency of topical HA and vitamin C and transdermal lopinavir delivery. Moreover, the efficiency and safety of transdermal delivery using the RED system were comparable with those of a commercial ketoprofen patch formulation. Thus, the RED system can be a potential topical and transdermal delivery system for various poorly bioavailable pharmaceuticals including HA, vitamin C, and lopinavir.</p