Neural representation of valenced and generic probability and uncertainty.

Representing the probability and uncertainty of outcomes facilitates adaptive behavior by allowing organisms to prepare in advance and devote attention to relevant events. Probability and uncertainty are often studied only for valenced (appetitive or aversive) outcomes, raising the question whether the identified neural machinery also processes the probability and uncertainty of motivationally neutral outcomes. Here, we aimed to dissociate valenced from valence-independent (i.e., generic) probability (p; maximum at p=1) and uncertainty (maximum at p=0.5) signals using human neuroimaging. In a Pavlovian task (n=41; 19 females), different cues predicted appetitive, aversive, or neutral liquids with different probabilities (p=0, p=0.5, p=1). Cue-elicited motor responses accelerated, and pupil sizes increased primarily for cues that predicted valenced liquids with higher probability. For neutral liquids, uncertainty rather than probability tended to accelerate cue-induced responding and decrease pupil size. At the neural level, generic uncertainty signals were limited to occipital cortex, while generic probability also activated anterior ventromedial prefrontal cortex. These generic probability and uncertainty signals contrasted with cue-induced responses that only encoded the probability and uncertainty of valenced liquids in medial prefrontal, insular and occipital cortices. Our findings show that the brain processes probability and uncertainty in a generic fashion. Moreover, the behavioral and neural dissociation of generic and valenced signals indicates that the brain keeps track of motivational charge and highlights the need and usefulness of characterizing the exact nature of learned representations.Significance Statement Encoding the probability and uncertainty of outcomes is important for adaptive behavior. Here we ask to what extent the brain represents probability and uncertainty regardless of whether the predicted outcomes are valenced (i.e. motivationally relevant) or generic (i.e., valence-independent). We dissociate generic from valenced variables by using not only cues that predict appetitive or aversive outcomes, but also cues that predict neutral outcomes. Our data reveal distinct behavioral effects and largely separate neural representations of valenced and generic variables. For example, valenced probability activated more proximal parts of medial prefrontal and occipital cortex whereas generic probability activated more distal parts. Thus, the representation of probability and uncertainty is multiplexed, allowing for tailored information processing according to computational needs.

Mechanism of kisspeptin neuron synchronization for pulsatile hormone secretion in male mice.

The mechanism by which arcuate nucleus kisspeptin (ARNKISS) neurons co-expressing glutamate, neurokinin B, and dynorphin intermittently synchronize their activity to generate pulsatile hormone secretion remains unknown. An acute brain slice preparation maintaining synchronized ARNKISS neuron burst firing was used alongside in vivo GCaMP GRIN lens microendoscope and fiber photometry imaging coupled with intra-ARN microinfusion. Studies in intact and gonadectomized male mice revealed that ARNKISS neuron synchronizations result from near-random emergent network activity within the population and that this was critically dependent on local glutamate-AMPA signaling. Whereas neurokinin B operated to potentiate glutamate-generated synchronizations, dynorphin-kappa opioid tone within the network served as a gate for synchronization initiation. These observations force a departure from the existing "KNDy hypothesis" for ARNKISS neuron synchronization. A "glutamate two-transition" mechanism is proposed to underlie synchronizations in this key hypothalamic central pattern generator driving mammalian fertility.

Development of AE147 Peptide-Conjugated Nanocarriers for Targeting uPAR-Overexpressing Cancer Cells.

PURPOSE: An AE147 peptide-conjugated nanocarrier based on PEGylated liposomes was developed in order to target the metastatic tumors overexpressing urokinase-type plasminogen activator receptor (uPAR), which cancer progression via uPA signaling. Therefore, the AE147 peptide-conjugated nanocarrier system may hold the potential for active targeting of metastatic tumors. METHODS: The AE147 peptide, an antagonist of uPAR, was conjugated to the PEGylated liposomes for targeting metastatic tumors overexpressing uPAR. Docetaxel (DTX), an anticancer drug, was incorporated into the nanocarriers. The structure of the AE147-conjugated nanocarrier, its physicochemical properties, and in vivo biodistribution were evaluated. RESULTS: The DTX-loaded nanocarrier showed a spherical structure, a high drug-loading capacity, and a high colloidal stability. Drug carrying AE147 conjugates were actively taken up by the uPAR-overexpressing MDA-MB-231 cancer cells. In vivo animal imaging confirmed that the AE147-conjugated nanoparticles effectively accumulated at the sites of tumor metastasis. CONCLUSION: The AE147-nanocarrier showed potential for targeting metastatic tumor cells overexpressing uPAR and as a nanomedicine platform for theragnosis applications. These results suggest that this novel nano-platform will facilitate further advancements in cancer therapy.

Photo-Based Nanomedicines Using Polymeric Systems in the Field of Cancer Imaging and Therapy.

The use of photo-based nanomedicine in imaging and therapy has grown rapidly. The property of light in converting its energy into different forms has been exploited in the fields of optical imaging (OI) and phototherapy (PT) for diagnostic and therapeutic applications. The development of nanotechnology offers numerous advantages to overcome the challenges of OI and PT. Accordingly, in this review, we shed light on common photosensitive agents (PSAs) used in OI and PT; these include fluorescent and bioluminescent PSAs for OI or PT agents for photodynamic therapy (PDT) and photothermal therapy (PTT). We also describe photo-based nanotechnology systems that can be used in photo-based diagnostics and therapies by using various polymeric systems.

An On-Demand pH-Sensitive Nanocluster for Cancer Treatment by Combining Photothermal Therapy and Chemotherapy.

Combination therapy is considered to be a promising strategy for improving the therapeutic efficiency of cancer treatment. In this study, an on-demand pH-sensitive nanocluster (NC) system was prepared by the encapsulation of gold nanorods (AuNR) and doxorubicin (DOX) by a pH-sensitive polymer, poly(aspartic acid-graft-imidazole)-PEG, to enhance the therapeutic effect of chemotherapy and photothermal therapy. At pH 6.5, the NC systems formed aggregated structures and released higher drug amounts while sustaining a stable nano-assembly, structured with less systemic toxicity at pH 7.4. The NC could also increase antitumor efficacy as a result of improved accumulation and release of DOX from the NC system at pHex and pHen with locally applied near-infrared light. Therefore, an NC system would be a potent strategy for on-demand combination treatment to target tumors with less systemic toxicity and an improved therapeutic effect.

Deactivation of Ni-Al-Based Catalysts for Autothermal Reforming of Diesel Surrogate Fuel in the Presence of an Aromatic Hydrocarbon.

Diesel fuel can produce higher concentrations of H2 and CO gases than other types of hydrocarbon fuels via a reforming reaction for solid oxide fuel cells (SOFCs). However, in addition to sulfur compounds and aromatic hydrocarbons in diesel fuel are a major cause of catalyst deactivation. To elucidate the phenomenon of catalyst deactivation in the presence of an aromatic hydrocarbon, dodecane (C12H26) and hexadecane (C16H34) were blended with an aromatic hydrocarbon such as 1-methylnaphthalene (C11H10) to obtain a diesel surrogate fuel. The experiments were performed for autothermal reforming of the diesel surrogate fuel under conditions of S/C = 1.17, O2/C = 0.24, 750°C and GHSV= 12,000 h-1. Three Ni-Al-based catalysts with 10 wt% (N10A), 30 wt% (N30A) and 50 wt% (N50A) of NiO were prepared via the polymer modified incipient method. Whereas all of the Ni-Al-based catalysts were deactivated with increasing reaction time, the catalysts with greater Ni contents tended to maintain their catalytic performance for a longer time. Correlation between the catalytic performances and Ni content were analyzed by temperature-programmed reduction (TPR), Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscope with energy-dispersive X-ray spectroscopy (SEM-EDX), Brunauer-Emmett-Teller(BET) analysis, X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). Also, we concluded that ethylene (C2H4), which was detected by gas chromatography-mass spectrometry (GC-MS), was the fundamental cause of deactivation of the Ni-Al-based catalysts by accelerating the deposition of wire-type carbon on the catalytic surface.

Effects of Thin-Film Thickness on Sensing Properties of SnO2-Based Gas Sensors for the Detection of H2S Gas at ppm Levels.

SnO2 thin-film gas sensors were easily created using the ion sputtering technique. The as-deposited SnO2 thin films consist of a tetragonal SnO2 phase and densely packed nanosized grains with diameters of approximately 20-80 nm, which are separated by microcracks. The as-deposited SnO2 thin film is well crystallized, with a dense columnar nanostructure grown directly onto the alumina material and the Pt electrodes. The grain size and thickness of SnO2 thin films are easily controlled by varying the sputtering time of the ion coater. The responses of the SnO2 thin-film sensors decrease as the SnO2 film thickness is increased, indicating that a negative association exists between the sensor response and the SnO2 film thickness due to gas diffusion from the surface. The SnO2 thin-film sensor, which was created by ion sputtering for 10 min, shows an excellent sensor response (Ra/Rg where Ra is the electric resistance under air and Rg is the electric resistance under the test gas) for detecting 1 ppm H2S at 350°C.

Biochip Performances of Agarose, Poly(Oligo(Ethylene Glycol) Methacrylate), and Poly(2-Hydroxyethyl Methacrylate) Film on Glass Surfaces.

We demonstrate the biochip efficacies of three different polymer films (agarose, poly(oligo(ethylene glycol) methacrylate) (pOEGMA), and poly(2-hydroxyethyl metacharylate) (pHEMA) on microscopic glass surfaces. As a result, the non-biofouling performances increased in this order: agarose < pOEGMA < pHEMA, and the binding capabilities increased in this order: pHEMA < pOEGMA < agarose.

Principles and applications of nanomaterial-based hyperthermia in cancer therapy.

Over the past few decades, hyperthermia therapy (HTT) has become one of the most promising strategies to treat cancer. HTT has been applied with nanotechnology to overcome drawbacks such as non-selectivity and invasiveness and to maximize therapeutic efficacy. The high temperature of HTT induces protein denaturation that leads to apoptosis or necrosis. It can also enhance the effects of other cancer therapies because heat-damaged tissues reduce radioresistance and help accumulate anticancer drugs. Gold nanoparticles and superparamagnetic iron oxide with different energy sources are commonly used as hyperthermia agents. New types of nanoparticles such as those whose surface is coated with several polymers and those modified with targeting moieties have been studied as novel HTT agents. In this review, we introduce principles and applications of nanotechnology-based HTT using gold nanoparticles and superparamagnetic iron oxide.

Co-delivery of D-(KLAKLAK)2 Peptide and Chlorin e6 using a Liposomal Complex for Synergistic Cancer Therapy.

Nanotechnology-based photo-chemo combination therapy has been extensively investigated to improve therapeutic outcomes in anticancer treatment. Specifically, with the help of a singlet oxygen generated by the photosensitizer, the endocytosed nanoparticles are allowed to escape from the endosomal compartment, which is currently an obstacle in nanotechnology-based anticancer therapy. In this study, a liposomal complex system (Lipo (Pep, Ce6)), composed of a chlorin e6-conjugated di-block copolymer (PEG-PLL(-g-Ce6)) and a D-(KLAKLAK)2 peptide loading liposome (Lipo (Pep)), was developed and evaluated for its anticancer activity. Due to the membrane lytic ability of the D-(KLAKLAK)2 peptide and the membrane disruptive effect of the singlet oxygen generated from chlorin e6, Lipo (Pep, Ce6) accelerated the disruption of the endosomal compartment, and exhibited strong synergistic anticancer activity in vitro. The prepared liposomal complex system could potentially maximize the efficacy of the nanotechnology-based photo-chemo combination therapy, and can be regarded as a novel, versatile strategy in advanced tumor therapy.

Surface Functionalization of Plastic Surfaces with Non-Biofouling Agarose Film to Develop a Chip-Based Platform.

We chemically functionalized several plastic surfaces using an agarose film for applying a protein chip. The chip performance was affected by the surface energy of each plastic after oxygen-plasma cleaning; as a result, polystyrene and polyethylene terephthalate showed a higher signal-to-noise ratio than did polypropylene. We envision that this study will help to develop a way to build biochips.

Reliable new measures capturing low-frequency fluctuations from resting-state functional MRI.

Resting-state functional MRI (rsfMRI) is one of the most important neuroimaging modalities for investigating alterations in the resting-state networks of the human brain, given that abnormal neural activity during the resting state is associated with neurological disorders. However, neuroimaging results obtained from rsfMRI have rarely been replicated with repeated measurements. Therefore, we aimed to develop new measures to extract highly reliable and reproducible functional neuroimaging metrics from rsfMRI data. Preprocessed rsfMRI data from 30 patients with 10 sessions of rsfMRI scans taken within 1 month were obtained from the Consortium for Reliability and Reproducibility. We developed a time-domain measure to capture low-frequency fluctuation (LFF) using a general linear model with three different periodic regressors: boxcar, triangular, and sinusoidal functions. Then, test-retest reliability for the proposed methods was evaluated using the intraclass correlation (ICC). Our approaches for evaluating LFF from rsfMRI data significantly identified the default mode network areas (corrected P<0.05). The regression model with the sinusoidal basis function produced the most reliable results (ICC=0.6) compared with the boxcar (ICC=0.32) or triangular (ICC=0.34) functions. Taken together, the proposed methods successfully identified the default mode network regions. In addition, our results suggest that new functional metrics aiming to extract LFF components by modeling rsfMRI time-series data might provide a reliable biomarker to identify neurological disorders accompanying abnormal functional activity.

The left middle temporal gyrus in the middle of an impaired social-affective communication network in social anxiety disorder.

BACKGROUND: Previous studies on patients diagnosed with social anxiety disorder (SAD) reported changed patterns of the resting-state functional connectivity network (rs-FCN) between the prefrontal cortices and other prefrontal, amygdalar or striatal regions. Using a graph theory approach, this study explored the modularity-based community profile and patterns of inter-/intra-modular communication for the rs-FCN in SAD. METHODS: In total, for 28 SAD patients and 27 healthy controls (HC), functional magnetic resonance imaging (fMRI) data were acquired in resting-state and subjected to a graph theory analysis. RESULTS: The within-module degree z-score for a hub region [out of a total of 10 hub regions ranked using the participation coefficient] named left middle temporal gyrus was impaired in SAD compared to HC, proportional to the severity of clinician-scored and patient-reported functional impairment in SAD. LIMITATIONS: Most of participants included in this study were undergraduate students in their early-to-mid 20's. CONCLUSIONS: This study showed the importance of functional communication from the left middle temporal gyrus with other opercular-insular-subcortical regions for better objective functioning and lesser subjective disability in SAD.

Improvement of H2S sensing properties of SnO2-based thick film gas sensors promoted with MoO3 and NiO.

The effects of the SnO2 pore size and metal oxide promoters on the sensing properties of SnO2-based thick film gas sensors were investigated to improve the detection of very low H2S concentrations (<1 ppm). SnO2 sensors and SnO2-based thick-film gas sensors promoted with NiO, ZnO, MoO3, CuO or Fe2O3 were prepared, and their sensing properties were examined in a flow system. The SnO2 materials were prepared by calcining SnO2 at 600, 800, 1,000 and 1,200 °C to give materials identified as SnO2(600), SnO2(800), SnO2(1000), and SnO2(1200), respectively. The Sn(12)Mo5Ni3 sensor, which was prepared by physically mixing 5 wt% MoO3 (Mo5), 3 wt% NiO (Ni3) and SnO2(1200) with a large pore size of 312 nm, exhibited a high sensor response of approximately 75% for the detection of 1 ppm H2S at 350 °C with excellent recovery properties. Unlike the SnO2 sensors, its response was maintained during multiple cycles without deactivation. This was attributed to the promoter effect of MoO3. In particular, the Sn(12)Mo5Ni3 sensor developed in this study showed twice the response of the Sn(6)Mo5Ni3 sensor, which was prepared by SnO2(600) with the smaller pore size than SnO2(1200). The excellent sensor response and recovery properties of Sn(12)Mo5Ni3 are believed to be due to the combined promoter effects of MoO3 and NiO and the diffusion effect of H2S as a result of the large pore size of SnO2.

Effects of textural properties on the response of a SnO2-based gas sensor for the detection of chemical warfare agents.

The sensing behavior of SnO(2)-based thick film gas sensors in a flow system in the presence of a very low concentration (ppb level) of chemical agent simulants such as acetonitrile, dipropylene glycol methyl ether (DPGME), dimethyl methylphosphonate (DMMP), and dichloromethane (DCM) was investigated. Commercial SnO(2) [SnO(2)(C)] and nano-SnO(2) prepared by the precipitation method [SnO(2)(P)] were used to prepare the SnO(2) sensor in this study. In the case of DCM and acetonitrile, the SnO(2)(P) sensor showed higher sensor response as compared with the SnO(2)(C) sensors. In the case of DMMP and DPGME, however, the SnO(2)(C) sensor showed higher responses than those of the SnO(2)(P) sensors. In particular, the response of the SnO(2)(P) sensor increased as the calcination temperature increased from 400 °C to 800 °C. These results can be explained by the fact that the response of the SnO(2)-based gas sensor depends on the textural properties of tin oxide and the molecular size of the chemical agent simulant in the detection of the simulant gases (0.1-0.5 ppm).

Dual-mode operation of a twisted nematic liquid crystal cell by switching between dynamic and memory modes.

We propose a twisted nematic liquid crystal device that can be operated in dynamic or memory mode, based on the information content to be displayed at that time. +90°-twisted and -90°-twisted states are used as two stable states for operation in the memory mode. A vertical electric field is applied to realize gray levels for operation in the dynamic mode. The proposed device has a memory retention time of over a month for the memory mode and a response time of 12 ms for the dynamic mode. Contrast ratios of over 500∶1 can be obtained in both the dynamic and memory modes.

Fast polarization switching panel with high brightness and contrast ratio for three-dimensional display.

We propose a polarization switching device using optically compensated pi cell for polarization-glass-type three-dimensional display. This device shows good optical properties such as high transmittance and low cross-talk ratio because of its fast dynamic response characteristics. To improve the brightness and contrast ratio on the right- and left-hand sides, we attach optical retardation films on each side of the polarization glasses instead of attaching the films on the polarization switching panel. From the calculation and experiment, we obtain high contrast ratios, over 200:1, on both sides and a high brightness using only one film on each side.

Switching of liquid-crystal devices between reflective and transmissive modes using long-pitch cholesteric liquid crystals.

We propose liquid-crystal (LC) devices capable of switching between reflective and transmissive modes using the scattering and transparent states of long-pitch cholesteric LCs (CLCs). Two different device configurations can be realized by changing the location of a CLC layer. Low-power operation without the parallax problem can be achieved using the bistable switching of CLCs. We believe that the proposed devices are potential candidates for highly efficient transflective displays.

Optical configurations for nematic liquid crystal device switchable between reflective and transmissive modes.

We propose an optical configuration for a nematic liquid crystal (LC) device that is switchable between the reflective and the transmissive modes. By placing a reflective polarizer between the two LC layers, we obtain higher reflectance and reduce the parallax effect in the reflective mode. We can eliminate the parallax effect by using a wire-grid polarizer or other in-cell reflective polarizers. We expect that the proposed device can be used in various outdoor applications.

Long-pitch cholesteric liquid crystal cell for switchable achromatic reflection.

We propose a switchable achromatic reflector using a long-pitch cholesteric liquid crystal (CLC) whose Bragg reflection wavelength is chosen to be infrared by controlling the pitch of the CLC so that the planar texture is transparent over the entire visible wavelength. By using the light scattering of the focal conic texture, achromatic reflection can be achieved. Both textures are stable at zero electric field and the operating voltage of the proposed CLC device is much lower than that of conventional CLC devices. The proposed switchable reflector, which can be operated at a low voltage with low power, can be applied to reflective displays and to light shutters. By coupling with a reflective polarizer the efficiency of light scattering at the focal conic texture can be enhanced.