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Over 4% of the global population is estimated to live with autoimmune disease, necessitating immunosuppressive treatment that is often chronic, not curative, and carries associated risks. B cells have emerged as key players in disease pathogenesis, as evidenced by partial responsiveness to B cell depletion by antibody-based therapies. However, these treatments often have transient effects due to incomplete depletion of tissue-resident B cells. Chimeric antigen receptor (CAR) T cells targeting B cells have demonstrated efficacy in refractory systemic lupus erythematosus. To this end, we developed an anti-CD19 CAR T cell product candidate, CABA-201, containing a clinically evaluated fully human CD19 binder (IC78) with a 4-1BB costimulatory domain and CD3 zeta stimulation domain for treatment refractory autoimmune disease. Here, we demonstrate specific cytotoxic activity of CABA-201 against CD19+ Nalm6 cells with no off-target effects on primary human cells. Novel examination of CABA-201 generated from primary T cells from multiple patients with autoimmune disease displayed robust CAR surface expression and effective elimination of the intended target autologous CD19+ B cells in vitro. Together, these findings support the tolerability and activity of CABA-201 for clinical development in patients with autoimmune disease.

The open reduction of mandibular condyle neck fractures is difficult due to the limited surgical field and complex facial nerve structures. The most effective fixation method for narrow fractured segments is debated as standard double four-hole plate fixation is often not feasible. This research compared bone stability and force resistance between single-long-plate and double-short-plate fixations using clinical outcomes, a Sawbones mandible model, and finite element analysis. In patients with condyle neck fractures, nine were fixed with single-long-plate and twelve with double-short-plate fixations, with no significant differences in malocclusion and facial palsy rates. In compression tests with a Sawbones model, displacements in the posterior part were similar in both fixation groups. In contrast, the anterior part had significantly higher displacements in the single-long-plate group. Finite element analysis showed higher displacements in both anterior and posterior parts in the single-plate group compared to the double-short-plate group. Maximum stresses were at the second screw hole in single-long-plate fixation and the turning point of the upper plate at the condyle neck in double-short-plate fixation. Double-short-plate fixations demonstrated better stability and force resistance than single-long-plate fixations.

Abstract Effects of type 2 diabetes on achromatic and chromatic contrast sensitivity (CS) are still controversial. In this study, we aimed to investigate CS in patients without diabetic retinopathy (no-DR) and in those with non-proliferative DR (NPDR) and proliferative DR (PDR) using psychophysical methods with transient and sustained achromatic stimuli and color patches. Achromatic CS was measured with the pulsed pedestal (PP) paradigm (7, 12, and 19 cd/m2) and pedestal-△-pedestal (P-△-P) paradigm (11.4, 18, and 28.5 cd/m2). A chromatic discrimination paradigm that assesses protan, deutan, and tritan color vision was adopted. Forty-two patients (no-DR n = 24, NPDR n = 12, PDR = 6; male n = 22, mean age = 58.1 y/o) and 38 controls (male n = 18, mean age = 53.4 y/o) participated. In patients, mean thresholds were higher than in controls and linear trends were significant in most conditions. For the PP paradigm, differences were significant in the PDR and NPDR groups in the 7 and 12 cd/m2 condition. For the P-△-P paradigm, differences were only significant in the PDR group in the 11 cd/m2 condition. Chromatic contrast loss was significant in the PDR group along the protan, deutan and tritan axes. The results suggest independent involvements of achromatic and chromatic CS in diabetic patients.

Abstract We investigated lateral modulation effects with functional magnetic resonance imaging. We presented radial sinusoidal gratings in random sequence: a scotoma grating with two arc-shaped blank regions (scotomata) in the periphery, one in the left and one in the right visual field, a center grating containing pattern only in the scotoma regions, and a full-field grating where the pattern occupied the whole screen. On each trial, one of the three gratings flickered in counterphase for 10 s, followed by a blank period. Observers were instructed to perform a fixation task and report whether filling-in was experienced during the scotoma condition. The results showed that the blood-oxygen-level-dependent signal was reduced in areas corresponding to the scotoma regions in the full-field compared to the center condition in V1 to V3 areas, indicating a lateral inhibition effect when the surround was added to the center pattern. The univariate analysis results showed no difference between the filling-in and no-filling-in trials. However, multivariate pattern analysis results showed that classifiers trained on activation pattern in V1 to V3 could differentiate between filling-in and no-filling-in trials, suggesting that the neural activation pattern in visual cortex correlated with the subjective percept.

Abstract Background Precision is crucial in determining the appropriate procedure for implementing further trials. We conducted a study to explore the reliability of a novel measuring system for human skin color. Methods The novel skin color measuring system was used to capture the skin color of four volunteers (2 males and 2 females) from the same location on each subject by the same operator. The measurement was repeated for different poses and instrument factors (camera and shooting protocol) in the red, green, and blue (RGB) system. The average color depth in each image was calculated and converted from 0 to 255. The spread of measures and the Bland‐Altman plot was displayed to determine each variance source's random error, with the interclass correlation coefficients applied to reflect the reliability. Result The RGB color depth in the experiment ranged from 190, 152, and 122 to 208, 170, and 142. The 95% confidential interval of the differences from the means in RGB colors for the different protocols were ±2.8, ±2.6, and ±2.1, respectively. The largest variation in the replicate trials was observed when subjects were in a supine position (standard deviation: 2). The interclass correlation coefficients were greater than 90%, suggesting that the developed system is highly precise. Conclusion This study demonstrated that the developed device could stably and reliably detect human skin color across different common sources of variation, and thus could be applied clinically to explore relationships between health/disease and skin color changes.

Abstract Collinear search impairment (CSI) is a phenomenon where a task-irrelevant collinear structure impairs a target search in a visual display. It has been suggested that CSI is monocular, occurs without the participants’ access to consciousness and is possibly processed at an early visual site (e.g. V1). This effect has frequently been compared with a well-documented opposite effect called attentional capture (AC), in which salient and task-irrelevant basic features (e.g. color, orientation) enhance target detection. However, whether this phenomenon can be attributed to non-attentional factors such as collinear facilitation (CF) has not yet been formally tested. Here we used one well-established property of CF, i.e. that target contrast modulates its effect direction (facilitation vs suppression), to examine whether CSI shared similar signature profiles along different contrast levels. In other words, we tested whether CSI previously observed at the supra-threshold level was reduced or reversed at near-threshold contrast levels. Our results showed that, regardless of the luminance contrast levels, participants spent a longer time searching for targets displayed on the salient singleton collinear structure than those displayed off the structure. Contrast invariance suggests that it is unlikely that CSI is exclusively sub-served by an early vision mechanism (e.g. CF).

Background:. Management of comminuted facial fractures with maxillary-mandibular arch interruption is difficult, resulting in inadequate bone reduction and malocclusion. Traditionally, a good quality dental splint is helpful, but difficult to obtain in acute trauma. We apply a computer-assisted design and three-dimensional printing technology to improve splint fabrication and utilization, thus facilitating restoration of dental occlusion and facial fracture. Methods:. We retrospectively reviewed patients who suffered from facial fractures with interruption of the maxillary-mandibular arches. We developed the “computer-assisted reverse planning and three-dimensional printing model surgery” algorithm and applied it in selected patients. An occlusal splint was created as a surgical guide to enhance the maxilla-mandibular unit repair by taking care of the bone reduction and occlusion. All included patients were followed up to assess the functional outcome and patients suitable for this method. Results:. From Jan 2015 to Aug 2020, 10 patients (eight men and two women) with comminuted facial fractures were included. The average time of surgery was 9.2 days. The average follow-up time was 8.6 months. There was no patient who needed major revision to correct malocclusion or facial asymmetry. Conclusions:. A computer-assisted design splint decreases intraoperative inaccuracies and difficulty in comminuted maxillo-mandibular fractures. It is a useful and reliable alternative. Collaboration with an experienced engineer and patient selection are indispensable in delivering successful outcomes. Patients who have more than three bone fragments in a single dental arch or more than four bone fragments in the entire maxillary-mandibular unit appear to be excellent candidates for this method.

Objective: Lower serum low-density lipoprotein cholesterol (LDL-C) levels are associated with increased intracerebral hemorrhage (ICH) risk. However, reverse causality and residual confounding has not attracted public attention. Therefore, we assessed whether people with LDL-C have increased risk of mortality adjusting for potential confounders using two large Taiwan cohorts.Methods: The Mei-Jhao (MJ) cohort has 414,372 adults participating in a medical screening program with 378 ICH deaths within 15 years of follow-up (1994–2008). Cox proportional hazards regressions estimated hazard death ratios according to LDL-C levels. We identified 4,606 ICH patients from the Taiwan Stroke Registry (TSR) and analyzed the impact of LDL-C on 3-month mortality.Results: Low cholesterol (LDL-C

Photonic crystals possess metastructures with a unique dispersion relation. An integrated optical circuit plays a crucial role in quantum computing, for which miniaturized optical components can be designed according to the characteristics of photonic crystals. Because the stable light transmission mode for a square waveguide is transverse electric or transverse magnetic polarization, we designed a half-waveplate element with a photonic crystal that can rotate the polarization direction of the light incident on a waveguide by 90°. Using the dispersion relation of photonic crystals, the polarization rotation length and the optical axis’s angle of deviation from the electric field in the eigenmode can be effectively calculated. Polarization rotators designed on the basis of photonic crystal structures can effectively reduce the insertion loss of components and exhibit favorable polarization rotation performance.

In a stimulus with multiple moving elements, an observer may perceive that the whole stimulus moves in unison if (a) one can associate an element in one frame with one in the next (correspondence) and (b) a sufficient proportion of correspondences signal a similar motion direction (coherence). We tested the necessity of these two conditions by asking the participants to rate the perceived intensity of linear, concentric, and radial motions for three types of stimuli: (a) random walk motion , in which the direction of each dot was randomly determined for each frame, (b) random image sequence , which was a set of uncorrelated random dot images presented in sequence, and (c) global motion , in which 35% of dots moved coherently. The participants perceived global motion not only in the global motion conditions but also in the random image sequences, though not in random walk motion. The type of perceived motion in the random image sequences depends on the spatial context of the stimuli. Thus, although there is neither a fixed correspondence across different frames nor a coherent motion direction, observers can still perceive global motion in the random image sequence. This result cannot be explained by motion energy or local aperture border effects.

Immunotherapy is one of the most promising forms of cancer treatment. In particular, immune checkpoint blockers (ICBs) represent some of the leading candidates which many drug developers have heavily invested in. During pre-clinical development and prior to human clinical trials, animal tests are a critical component for determining the safety and efficacy of newly developed ICBs for cancer treatment. In this study, we strive to demonstrate the feasibility of using hollow fiber assay microtube array membrane (MTAM-HFA) in the screening of anti-cancer ICBs. The MTAM-HFA process was carried out by encapsulating peripheral blood mononuclear cells (PBMCs) and the target cancer cells (cell lines or primary cells) and subcutaneously implanting them into Balb/C mice. At predetermined time points combination regimens of PD-1/PD-L1+ were administered accordingly and at a predetermined time point, the MTAMs were retrieved, and cell viability assays were carried out. The outcomes of the MTAM-HFA were compared against the clinical outcome of patients. Clinical comparison demonstrated excellent correlation between the screening outcome of MTAM-HFA of PD-1/PD-L1+ combination therapy and the clinical outcome of the lung cancer patients. Basic cell studies revealed that the utilization of MTAM-HFA in PD-1/PD-L1+ combination therapy revealed enhanced T-cell activity upon the administration of the PD-1/PD-L1 drug; thereby resulting in the reduction of tumor cell viability by up to 70%, and the cytotoxic effects by 82%. The outcome was echoed in the in vivo cell studies. This suggested that the MTAM-HFA system is suitable for use in PD-1/PD-L1+ screening and the accuracy, rapidity and cost effectiveness made it extremely suitable for application as a companion diagnostic system in both personalized medicine for cancer treatment and could potentially be applied to screen for candidate compounds in the development of next generation PD-1/PD-L1+ combination therapies.

Coronary artery disease is one of the major diseases that plagues today’s modern society. Conventional treatments utilize synthetic vascular grafts such as Dacron® and Teflon® in bypass graft surgery. Despite the wide adaptation, these synthetic grafts are often plagued with weaknesses such as low hemocompatibility, thrombosis, intimal hyperplasia, and risks of graft infection. More importantly, these synthetic grafts are not available at diameters of less than 6 mm. In view of these challenges, we strived to develop and adapt the electrospun Poly Lactic-co-Glycolic Acid (PLGA) Microtube Array Membrane (MTAM) vascular graft for applications smaller than 6 mm in diameter. Homogenously porous PLGA MTAMs were successfully electrospun at 5.5–8.5 kV under ambient conditions. Mechanically, the PLGA MTAMs registered a maximum tensile strength of 5.57 ± 0.85 MPa and Young’s modulus value of 1.134 ± 0.01 MPa; while MTT assay revealed that seven-day Smooth Muscle Cells (SMCs) and Human Umbilical Vein Endothelial Cells (HUVECs) registered a 6 times and 2.4 times higher cell viability when cultured in a co-culture setting in medium containing α-1 haptaglobulin. When rolled into a vascular graft, the PLGA MTAMs registered an overall degradation of 82% after 60 days of cell co-culture. After eight weeks of culturing, immunohistochemistry staining revealed the formation of a monolayer of HUVECs with tight junctions on the surface of the PLGA MTAM, and as for the SMCs housed within the lumens of the PLGA MTAMs, a monolayer with high degree of orientation was observed. The PLGA MTAM registered a burst pressure of 1092.2 ± 175.3 mmHg, which was sufficient for applications such as small diameter blood vessels. Potentially, the PLGA MTAM could be used as a suitable substrate for vascular engineering.

Oxytocin (OXT) has been implicated in adult neurogenesis. Here the authors show that CA3 pyramidal cells in the adult mouse hippocampus express OXT receptors and receive inputs from hypothalamic OXT neurons; activation of OXT signaling in CA3 pyramidal cells promotes the survival and maturation of newborn neurons in the dentate gyrus in a non-cell autonomous manner.

Previously, we successfully developed an extracorporeal endotoxin removal device (EERD) that is based on the novel next generation alternating microtube array membrane (MTAM-A) that was superior to the commercial equivalent. In this article, we demonstrated multiple different parameter modifications that led to multiple different types of novel new MTAM structures, which ultimately led to the formation of the MTAM-A. Contrary to the single layered MTAM, the MTAM-A series consisted of a superior packing density fiber connected in a double layered, alternating position which allowed for the greater fiber count to be packed per unit area. The respective MTAM variants were electrospun by utilizing our internally developed tri-axial electrospinning set up to produce the novel microstructures as seen in the respective MTAM variants. A key uniqueness of this study is the ability to produce self-arranged fibers into the respective MTAM variants by utilizing a single spinneret, which has not been demonstrated before. Of the MTAM variants, we observed a change in the microstructure from a single layered MTAM to the MTAM-A series when the ratio of surfactant to shell flow rate approaches 1:1.92. MTAM-A registered the greatest surface area of 2.2 times compared to the traditional single layered MTAM, with the greatest tensile strength at 1.02 ± 0.13 MPa and a maximum elongation of 57.70 ± 9.42%. The MTAM-A was selected for downstream immobilization of polymyxin B (PMB) and assembly into our own internally developed and fabricated dialyzer housing. Subsequently, the entire setup was tested with whole blood spiked with endotoxin; and benchmarked against commercial Toraymyxin fibers of the same size. The results demonstrated that the EERD based on the MTAM-A performed superior to that of the commercial equivalent, registering a rapid reduction of 73.18% of endotoxin (vs. Toraymyxin at 38.78%) at time point 15 min and a final total endotoxin removal of 89.43% (vs. Toraymyxin at 65.03%).

Within the spectrum of a natural image, the amplitude of modulation decreases with spatial frequency. The speed of such an amplitude decrease, or the amplitude spectrum slope, of an image affects the perceived aesthetic value. Additionally, a human observer would consider a symmetric image more appealing than they would an asymmetric one. We investigated how these two factors jointly affect aesthetic preferences by manipulating both the amplitude spectrum slope and the symmetric level of images to assess their effects on aesthetic preference on a 6-point Likert scale. Our results showed that the preference ratings increased with the symmetry level but had an inverted U-shaped relation to amplitude spectrum slope. In addition, a strong interaction existed between symmetry level and amplitude spectrum slope on preference rating, in that symmetry can amplify the amplitude spectrum slope’s effects. A quadratic function of the spectrum slope can describe such effects. That is, preference is an inverted U-shaped function of spectrum slope whose intercept is determined by the number of symmetry axes. The modulation depth of the quadratic function manifests the interaction between the two factors.

The treatment of cancer has evolved significantly in recent years with a strong focus on immunotherapy. Encapsulated Cell Therapy (ECT) for immunotherapy-based anti-cancer treatment is a unique niche within this landscape, where molecules such as signaling factors and antibodies produced from cells are encapsulated within a vehicle, with a host amount of benefits in terms of treatment efficacy and reduced side effects. However, traditional ECTs generally lie in two extremes; either a macro scale vehicle is utilized, resulting in a retrievable system but with limited diffusion and surface area, or a micro scale vehicle is utilized, resulting in a system that has excellent diffusion and surface area but is unretrievable in the event of side effects occurring, which greatly compromises the biosafety of patients. In this study we adapted our patented and novel electrospun Polysulfone (PSF) Microtube Array Membranes (MTAMs) as a ‘middle’ approach to the above dilemma, which possess excellent diffusion and surface area while being retrievable. Hybridoma cells were encapsulated within the PSF MTAMs, where they produced CEACAM6 antibodies to be used in the suppression of cancer cell line A549, MDA-MB-468 and PC 3 (control). In vitro and in vivo studies revealed excellent cell viability of hybridoma cells with continuous secretion of CEACAM6 antibodies which suppressed the MDA-MB-468 throughout the entire 21 days of experiment. Such outcome suggested that the PSF MTAMs were not only an excellent three-dimensional (3D) cell culture substrate but potentially also an excellent vehicle for the application in ECT systems. Future research needs to include a long term in vivo >6 months study before it can be used in clinical applications.

Basic color terms used in Mandarin Chinese have been controversial since first discussed by Berlin and Kay in 1969. Previous studies showed much inconsistency on what should be considered as basic color terms in Mandarin Chinese. In the present study, we investigated categories of color rather than merely the color terms used by Taiwanese native Mandarin speakers. Using samples conforming to the Berlin and Kay survey, various colors were chosen from a collection of Natural Color System (NCS) colored papers and mounted on a piece of neutral gray card. The card was then mounted on a touch-screen, under D65 illumination. Thirty-two single-character color related Mandarin terms were selected from a Chinese character database according to frequency of use. Participants were required to select the color sample that matched the term by pressing a virtual button on the touch screen. The results show that certain terms can be directly correlated to basic color terms in English, comparable with the results of Berlin and Kay's original study and those that followed. However, some terms, such as Mo ( ink), Tie ( iron), and Cai (vegetable), show a wide spread of term maps and inconsistent use among subjects. Principle component analysis (PCA) procedures were used to analysis the commodity of data among subjects. The findings suggest that the basic color categories among Mandarin Chinese speakers are similar to those found in the World Color Survey (WCS), but are represented by wide-spread and inconsistent color terms among speakers.

High matrix metalloproteinase 1 (MMP1) expression is associated with enhanced breast cancer growth and metastasis and also might predict poor prognosis. In this study, we further investigated the functional role of MMP1 and how it is upregulated in multi-drug resistant (MDR) breast cancer cells. By retrieving microarray data in GEO datasets and the survival data in the Kaplan Meier plotter, we observed that MMP1 is significantly upregulated in MCF-7/ADR cells compared to the parental MCF-7 cells, while high MMP1 expression is associated with worse overall survival (OS) and recurrence free survival (RFS) in breast cancer patients after systematic therapy. Functional studies showed that MMP1 overexpression significantly reduced the drug sensitivity in MCF-7 cells, while MMP1 knockdown substantially enhanced the sensitivity in MCF-7/ADR cells. By performing western blotting and immunofluorescent staining, we confirmed that MCF-7/ADR cells had enhanced mesenchymal properties than MCF-7 cells. In MCF-7 cells, enforced Slug expression resulted in significant MMP1 upregulation, while in MCF-7/ADR cells, Slug knockdown led to reduced MMP1 expression. By performing bioinformatic analysis, we observed that the promoter of MMP1 has three putative Slug binding sites. The following dual luciferase assay and ChIP-qPCR verified these three binding sites. Therefore, we infer that Slug enhances MMP1 transcription via directly binding to the promoter region in breast cancer cells, which is a previously unrecognized mechanism in the development of MDR.

The guided tissue regeneration (GTR) membrane is a barrier intended to maintain a space for alveolar bone and periodontal ligament tissue regeneration but prevent the migration of fast-growing soft tissue into the defect sites. This study evaluated the physical properties, in vivo animal study, and clinical efficacy of hydrophilic PLA95/β-TCP GTR membranes prepared by electrospinning (ES). The morphology and cytotoxicity of ES PLA95/β-TCP membranes were evaluated by SEM and 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) respectively. The cementum and bone height were measured by an animal study at 8 and 16 weeks after surgery. Fifteen periodontal patients were selected for the clinical trial by using a commercial product and the ES PLA95/β-TCP membrane. Radiographs and various indexes were measured six months before and after surgery. The average fiber diameter for this ES PLA95/β-TCP membrane was 2.37 ± 0.86 µm. The MTT result for the ES PLA95/β-TCP membrane showed negative for cytotoxicity. The significant differences in the cementum and bone height were observed between empty control and the ES PLA95/β-TCP membrane in the animal model (p < 0.05). Clinical trial results showed clinical attachment level (CAL) of both control and ES PLA95/β-TCP groups, with a significant difference from the pre-surgery results after six months. This study demonstrated that the ES PLA95/β-TCP membrane can be used as an alternative GTR membrane for clinical applications.

A plaid is a combination of two gratings whose orientations are orthogonal to each other with the same or similar contrasts. We used plaid patterns as stimuli to investigate the mechanisms underlying the detection of a plaid to understand how the visual system combines information from orientation-selective channels. We used a masking paradigm in which an observer was required to detect a target (either a spiral or a plaid) superimposed on a pedestal. We measured the target threshold versus pedestal contrast (TvC) functions at 7 pedestal contrasts for various target-pedestal combinations with a temporal 2AFC paradigm and a staircase procedure. All TvC functions, except the one with an orthogonal spiral pedestal, showed a dipper shape, although the position of the dip and the slope varied across conditions. The result can be explained by a multiple-mechanism divisive inhibition model, which contains several orientation-selective mechanisms. The response of each mechanism is the excitation of a linear filter divided by a broadband inhibitory input. The threshold is determined by a nonlinear combination of the responses of those mechanisms. Alternative models with mechanism(s) specific for plaid did not provide a better description of the data. Thus, a plaid pattern is mediated by a combination of orientation-selective mechanisms. An early plaid-specific mechanism is not necessary for plaid detection.

Symmetric patterns are more appealing to human observers than asymmetric ones. Here, we investigate the visual information processing mechanisms underlying this aesthetic preference. All stimuli were derived from phase scrambled versions of forty face or nature images. In addition to the scrambled images, there were four other types of test image: symmetric, in which one part of the image was a reflection of another around an axis; repetitive, in which one part of the image was a copy of the other; anti-symmetric, similar to symmetric but with the contrast of one side reversed; and interleaved patterns, in which half of the symmetric pattern was replaced by a scrambled image. The number of axes ranged from 1 to 16 for all image types. The task of our 20 observers was to give a preference rating to each image on a 6-point Lickert scale. The preference rating increased with the number of axes for all stimulus types. The observers showed a similar preference for symmetric and repetitive patterns and slightly less preference for anti-symmetric patterns. The preference for interleaved patterns was much less than for other types of stimuli. Preference for an image cannot be explained by either the ecological significance of its content or the slope of its amplitude spectrum. Instead, preference can be accounted for by the complexity of the image.

Poorly crystalline hydroxyapatite was improved so that it has better cell affinity in vitro. We studied the efficacy of a novel resorbable poorly crystalline hydroxyapatite-based biphasic calcium phosphate, BonaGraft, for bone regeneration in vivo. Materials and methods: The beagle was used as an animal model, and cylindrical artificial bone defects (3 mm in diameter and 6 mm long) were produced in the alveolar bone. The BonaGraft (ratio of poorly crystalline hydroxyapatite to b-tricalcium phosphate, 60:40) was used to fill in the defect, and unfilled defects served as a control group. At 5, 8 and 10 weeks after the operation, the size of the residual graft and new bone formation were evaluation by a histomorphometric analysis. In a clinical trial, 33 enrolled patients included 15 males and 18 females with ages ranging from 35 to 54 years. The main indications were ridge augmentation (n = 12), sinus lifting (n = 2), repair of periodontal disease (n= 14), and repair of radicular cysts (n= 5). The clinical outcomes of the surgery were primarily evaluated by clinical radiographs. Results: In the animal study, implanting BonaGraft produced greater new-bone formation (74.5% ± 1.0%) at 10 weeks postoperatively than that of the control (40.2% ± 0.3%). BonaGraft particles were gradually resorbed and substituted by bone. The in vivo graft resorption time and bone healing time of 12.1 weeks were mathematically determined by the least squares method. In the clinical test, all patients implanted with BonaGraft reported satisfactory clinical outcomes without major material-related side effects. According to the radiographic pictures, implantation of BonaGraft enhanced bone formation. Conclusion: According to the animal study results, BonaGraft has a suitable resorption period and satisfactory outcomes of new bone formation. The clinical study produced high satisfaction with clinical results both objectively and subjectively. For this reason, BonaGraft seems to be an alternative choice for a bone substitute in dental applications.

Polyaniline (PANI), an attractive conductive polymer, has been successfully applied in fabricating various types of enzyme-based biosensors. In this study, we have employed mesoporous silica SBA-15 to stably entrap horseradish peroxidase (HRP), and then deposited the loaded SBA-15 on the PANI modified platinum electrode to construct a GA/SBA-15(HRP)/PANI/Pt biosensor. The mesoporous structures and morphologies of SBA-15 with or without HRP were characterized. Enzymatic protein assays were employed to evaluate HRP immobilization efficiency. Our results demonstrated that the constructed biosensor displayed a fine linear correlation between cathodic response and H2O2 concentration in the range of 0.02 to 18.5 mM, with enhanced sensitivity. In particular, the current approach provided the PANI modified biosensor with improved stability for multiple measurements.

Polyaniline (PANI) has been shown to possess excellent catalytic activity toward oxygen reduction, however, this molecule may interfere with the electrochemical measurement of other targets when using a polyaniline modified platinum (PANI/Pt) electrode. In this study, we have demonstrated the considerable effects of dissolved oxygen on the sensing of hydrogen peroxide with the PANI/Pt electrode. Accordingly, we proposed a strategy to eliminate the influence of dissolved oxygen with oxygen scavengers. Our results indicated that as an oxygen scavenger sodium thiosulfate was very effective in the removal of dissolved oxygen from the sample solution, and had negligible effect on the quantification of hydrogen peroxide when its applied concentration was below 1 mM.

Perceived depth is conveyed by multiple cues, including binocular disparity and luminance shading. Depth perception from luminance shading information depends on the perceptual assumption for the incident light, which has been shown to default to a diffuse illumination assumption. We focus on the case of sinusoidally corrugated surfaces to ask how shading and disparity cues combine defined by the joint luminance gradients and intrinsic disparity modulation that would occur in viewing the physical corrugation of a uniform surface under diffuse illumination. Such surfaces were simulated with a sinusoidal luminance modulation (0.26 or 1.8 cy/deg, contrast 20%-80%) modulated either in-phase or in opposite phase with a sinusoidal disparity of the same corrugation frequency, with disparity amplitudes ranging from 0'-20'. The observers' task was to adjust the binocular disparity of a comparison random-dot stereogram surface to match the perceived depth of the joint luminance/disparity-modulated corrugation target. Regardless of target spatial frequency, the perceived target depth increased with the luminance contrast and depended on luminance phase but was largely unaffected by the luminance disparity modulation. These results validate the idea that human observers can use the diffuse illumination assumption to perceive depth from luminance gradients alone without making an assumption of light direction. For depth judgments with combined cues, the observers gave much greater weighting to the luminance shading than to the disparity modulation of the targets. The results were not well-fit by a Bayesian cue-combination model weighted in proportion to the variance of the measurements for each cue in isolation. Instead, they suggest that the visual system uses disjunctive mechanisms to process these two types of information rather than combining them according to their likelihood ratios.

In a reaction time task, people typically slow down following an error or conflict, each called post-error slowing (PES) and post-conflict slowing (PCS). Despite many studies of the cognitive mechanisms, the neural responses of PES and PCS continue to be debated. In this study, we combined high-density array EEG and a stop-signal task to examine event-related potentials of PES and PCS in sixteen young adult participants. The results showed that the amplitude of N2 is greater during PES but not PCS. In contrast, the peak latency of N2 is longer for PCS but not PES. Furthermore, error-positivity (Pe) but not error-related negativity (ERN) was greater in the stop error trials preceding PES than non-PES trials, suggesting that PES is related to participants' awareness of the error. Together, these findings extend earlier work of cognitive control by specifying the neural correlates of PES and PCS in the stop signal task.

Angiotensin-converting enzyme (ACE) has been implicated in multiple biological system, particularly cardiovascular diseases. However, findings associating ACE insertion/deletion polymorphism with hypertension or other related traits are inconsistent. Therefore, in a two-stage approach, we aimed to fine-map ACE in order to narrow-down the function-specific locations. We genotyped 31 single nucleotide polymorphisms (SNPs) of ACE from 1168 individuals from 305 young-onset (age ≤40) hypertension pedigrees, and found four linkage disequilibrium (LD) blocks. A tag-SNP, rs1800764 on LD block 2, upstream of and near the ACE promoter, was significantly associated with young-onset hypertension (p = 0.04). Tag-SNPs on all LD blocks were significantly associated with ACE activity (p-value: 10(-16) to

To examine the effect of illumination direction on the ability of observers to discriminate between faces, we manipulated the direction of illumination on scanned 3D face models. In order to dissociate the surface reflectance and illumination components of front-view face images, we introduce a symmetry algorithm that can separate the symmetric and asymmetric components of the face in both low and high spatial frequency bands. Based on this approach, hybrid faces stimuli were constructed with different combinations of symmetric and asymmetric spatial content. Discrimination results with these images showed that asymmetric illumination information biased face perception toward the structure of the shading component, while the symmetric illumination information had little, if any, effect. Measures of perceived depth showed that this property increased systematically with the asymmetric but not the symmetric low spatial frequency component. Together, these results suggest that (1) the asymmetric 3D shading information dramatically affects both the perceived facial information and the perceived depth of the facial structure; and (2) these effects both increase as the illumination direction is shifted to the side. Thus, our results support the hypothesis that face processing has a strong 3D component.

We used a noise masking paradigm to examine the interaction between color-selective symmetry detection mechanisms in the visual system. We used a 2AFC paradigm in which a random dot noise mask was presented in both intervals. One interval contained a target, while the other, a random dot control. The target consisted of a red and a green symmetric pattern with the same (both were 45° or −45°) or orthogonal (one 45°and the other −45°) orientation. The observers were to determine which interval contained the symmetric target. We measured the target density threshold at various noise densities. For all conditions, the target density threshold increased with noise density with a slope 0.96 on log-log coordinates. The threshold for the same-orientation condition was lower than that for the orthogonal condition at all noise densities. We fit our data with a divisive inhibition model for symmetry pattern detection (Chen & Tyler, 2010 PLOS One ), in which the response of a symmetry detector is the excitation of a linear symmetry operator raised to a power and then divided by the divisive inhibition from all relevant symmetry operators. The best fit showed that the mutual inhibition between symmetry detectors in the same-orientation condition was only 13% of that in the orthogonal condition. Hence, instead of a strong same-orientation inhibition commonly observed in experiments using Gabor patches, it is actually easier for the visual system to integrate symmetric patterns of the same symmetric axis.

Crowding refers to the phenomenon that the visual performance to a visual target deteriorates with the presence of nearby flankers. To investigate the mechanisms underlying crowding in object perception, we used Chinese characters as stimuli such that we can estimated the role of grouping and familiarity. The target was presented at 6 deg from the fixation. The flankers were placed to both sides of the target with a 1.5 deg center-to-center distance. The target and the flankers were either upright or inverted characters. When the target and the flankers were iso-orientation, in half of the trials, they might be combined into a compound character. The task of the observer was to decide whether the target is upright or inverted. Compared with the no flanker condition, the presence of the flankers reduced the percentage of correct response (accuracy) regardless of the character type or orientation. The accuracy for the iso-orientation conditions was always higher than that for the aniso-orientation conditions. The result is the same regardless whether the target and the flankers can be grouped into a compound word, hence cannot be explained by the word superior effect. Our result suggests two types of flanker effects: The first is a general crowding effect that reduces the visibility of the target whenever a flanker is presented and may result from an early visual mechanism. The second is specific to character orientation and thus should be mediated by a mechanism that tuned to visual word forms.

To identify the visual characteristics that make a scene looks nature, we investigated the relationship between the distribution of spatial frequency spectrum of an image and its perceived naturalness. The image database contains outdoor images whose perceived naturalness were rated by human observers. Each image was Fourier transformed to the frequency domain. The power spectrum of each image was radial averaged across orientation and then fit with a straight line on log-log coordinates. The slope of the fitted line represents the characteristics of the spatial frequency spectrum of the image. The perceived naturalness increased with the decrease of the spectrum slope. The correlation between these two factors was significant. That is, our result suggests that increasing high spatial frequency content makes a scene more nature for observers. Thus, increase high spatial frequency content in an urban visual environment by planting more trees and adding more detail object or separation line to the architecture façade should make it more like nature environment.

Contrast perception depends on not only the early visual responses, but also top-down modulations. We measured how does P300, a well-documented event-related potential (ERP) index for top-down influence, change with both spatial frequency and contrast. ERP were acquired from 10 participants, aged 18–50 years, when they were performing a visual oddball task. The target was a Gabor patch whose spatial frequency was either 4 or 8 cy/degree and contrasts 90% or 30%. The probability of target presence in a trial was 30%. All target stimuli produced a reliable P300 component. At the low spatial frequency, the amplitude of P300 was larger and the latency was shorter for the low contrast patterns than for the higher contrast ones for all electrodes. Such difference was not observed in high spatial frequency patterns. The latency was slightly longer for high spatial frequency patterns than the low spatial frequency ones. Our results showed an interaction between spatial frequency and contrast in P300. The characteristics of P300 at low spatial frequency correlated with task difficulty, but not at high spatial frequency. This suggests that the top-down influence on contrast perception may be spatial frequency depended.

Objective: Contrast perception could be influenced by top-down factors. We measured P300 component, a well-documented index for top-down influence in visual functions, to examine such effect. Methods: Twelve participants, 18- to 50-years old, with normal or correct-to-normal visual acuity participated in the study. Standard two-stimulus oddball paradigm was employed. Target stimuli were Gabor patch with 4 cy/degree spatial frequency and 90% contrast. In an attempt to mimic clinical population, event-related potential (ERP) was recorded in (1) the passive viewing condition, in which the participants were instructed to fixate at the center of screen; and (2) the active condition, in which the participants were required to press a button to indicate the presence of a target. Participants performed passive task before active task. The probability that a target was presented in a trial was either 50% or 30% in a run. P300 oddball effect was defined as the difference in ERP between 30% and 50% probability conditions. Results: A reliable P300 oddball effects was found under active condition. For passive viewing condition, P300 oddball effects were not apparent. Conclusion: The findings support the hypothesis that P300 reflects the task-dependent top-down effect in visual functions.

Symmetric patterns are more appealing to human observers than asymmetric ones. Here, we investigated the possible mechanisms underlying such preference. All Stimuli were derived from phase scrambled versions of forty face or nature images. There were four types of test images: symmetry, in which one part of the image was the reflective transform of the other part about an axis; repetition, one part of the image was a copy of the other part; anti-symmetry, similar to symmetry but the contrast of one side was reversed; and interleaved patterns, half of the symmetric pattern was replaced by a scrambled image. The number of axes ranged from 1 to 16 for all image types. The task of our 20 observers was to give a preference rating to each image on a 6-point Lickert Scale. The preference rating increased with the number of axis for all stimulus type. The preference to symmetry was similar to that to repetition and was slightly better than anti-symmetry. The preference to interleaved pattern was much less than other types of stimuli. The preference rating of an image has little correlation with the slope of the power spectrum but of the image but is inversely correlated with its complexity.

To perceive a symmetric pattern, an observer needs to find correspondence between two image elements across the symmetric axis, implying an excitatory relationship between perceptual mechanisms responding to these elements. To perceive a 3D structure in a random dot stereogram (RDS), the perceptual mechanisms tuned to different disparities would inhibit each other. We investigated whether putting corresponding elements of a symmetric pattern in different depths would affect symmetry detection. The symmetry patterns consisted of dots (0.19degx0.19deg) occupying .5% of the display. We measured the coherence threshold for detecting symmetric patterns rendered on 14 possible 3D structures that were produced by an RDS. The coherence threshold for symmetric patterns on a slant surface was similar to that on a frontoparallel plane even though in the former the depths of the two sides of the symmetric axis were different. The threshold increased dramatically when one side of the axis inclined toward the observer while the other side inclined away though the depth difference between the two sides was the same as that in the slant condition. The threshold reduced on a hinge configuration whose joint coincide with the symmetry axis. Our result suggests that co-planarity is a decisive factor for symmetry detection.

The visibility of a target pattern can be affected by the presence of an adjacent stimulus (flanker). Here, we showed that such lateral masking effect depends on both the phase and the position of the flanker. The task of the observers was to detect a 4 cy/deg vertical Gabor target with the presence of vertical flankers. The target was in sine phase related to the fixation. The flankers had either the same or the opposite phase as the target and located at either the collinear or the side position from the target. The distance between the target and the flanker varied from 2 to 7.5 wavelengths. We measured the target threshold at 75% correct level. Compared with the no-flanker condition, the same-phase collinear flankers and the opposite-phase side flankers significantly decreased target threshold while the other flankers had little effects. Hence the side flanker has an effect only if the bright region of the target is adjacent to the bight regions of the flanker, and the dark region of the target to the dark region of the flanker. This result is consistent with the notion of border ownership in which facilitation occurs when the target and the flankers signal the same border.

BACKGROUND: Visual processing network is one of the functional networks which have been reliably identified to consistently exist in human resting brains. In our work, we focused on this network and investigated the intrinsic properties of low frequency (0.01-0.08 Hz) fluctuations (LFFs) during changes of visual stimuli. There were two main questions to be discussed in this study: intrinsic properties of LFFs regarding (1) interactions between visual stimuli and resting-state; (2) impact of repetition rate of visual stimuli. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed scanning sessions that contained rest and visual stimuli in various repetition rates with a novel method. The method included three numerical approaches involving ICA (Independent Component Analyses), fALFF (fractional Amplitude of Low Frequency Fluctuation), and Coherence, to respectively investigate the modulations of visual network pattern, low frequency fluctuation power, and interregional functional connectivity during changes of visual stimuli. We discovered when resting-state was replaced by visual stimuli, more areas were involved in visual processing, and both stronger low frequency fluctuations and higher interregional functional connectivity occurred in visual network. With changes of visual repetition rate, the number of areas which were involved in visual processing, low frequency fluctuation power, and interregional functional connectivity in this network were also modulated. CONCLUSIONS/SIGNIFICANCE: To combine the results of prior literatures and our discoveries, intrinsic properties of LFFs in visual network are altered not only by modulations of endogenous factors (eye-open or eye-closed condition; alcohol administration) and disordered behaviors (early blind), but also exogenous sensory stimuli (visual stimuli with various repetition rates). It demonstrates that the intrinsic properties of LFFs are valuable to represent physiological states of human brains.

Symmetry detection is an interesting probe of pattern processing because it requires the matching of novel patterns without the benefit of prior recognition. However, there is evidence that prior knowledge of the axis location plays an important role in symmetry detection. We investigated how the prior information about the symmetry axis affects symmetry detection under noise-masking conditions. The target stimuli were random-dot displays structured to be symmetric about vertical, horizontal, or diagonal axes and viewed through eight apertures (1.2 degrees diameter) evenly distributed around a 6 degrees diameter circle. The information about axis orientation was manipulated by (1) cueing of axis orientation before the trial and (2) varying axis salience by including or excluding the axis region within the noise apertures. The percentage of correct detection of the symmetry was measured at for a range of both target and masking noise densities. The threshold vs. noise density function was flat at low noise density and increased with a slope of 0.75-0.8 beyond a critical density. Axis cueing reduced the target threshold 2-4 fold at all noise densities while axis salience had an effect only at high noise density. Our results are inconsistent with an ideal observer or signal-to-noise account of symmetry detection but can be explained by a multiple-channel model is which the response in each channel is the ratio between the nonlinear transform of the responses of sets of early symmetry detectors and the sum of external and intrinsic sources of noise.