Gold Nanorod-Embedded PDMS Micro-Pillar Array for Localized Photothermal Stimulation.

Gold nanorods (GNRs) are one of the most promising biomaterial choices for the photothermal activation of neurons due to their relative biocompatibility, unique photothermal properties, and broad optical tunability through their synthetic shape control. While photothermal stimulation using randomly accumulated GNRs successfully demonstrates the potential treatment of functional neural disorders by modulating the neuronal activities using localized heating, there are limited demonstrations to translate this new concept into large-arrayed neural stimulations. In this paper, we report an arrayed PDMS micropillar platform in which GNRs are embedded as pixel-like, arrayed photothermal stimulators at the tips of the pillars. The proposed platform will be able to localize GNRs at predetermined pillar positions and create thermal stimulations using near-infrared (NIR) light. This will address the limitations of randomly distributed GNR-based approaches. Furthermore, a flexible PDMS pillar structure will create intimate interfaces on target cells. By characterizing the spatiotemporal temperature change in the platform with rhodamine B dye, we have shown that the localized temperature can be optically modulated within 4°C, which is in the range of temperature variation required for neuromodulation using NIR light. We envision that our proposed platform has the potential to be applied as a photothermal, neuronal stimulation interface with high spatiotemporal resolution.

Hydrogel Micropillar Array for Temperature Sensing in Fluid.

Localized temperature sensing and control on a micron-scale have diverse applications in biological systems. We present a micron-sized hydrogel pillar array as potential temperature probes and actuators by exploiting sensitive temperature dependence of their volume change. Soft lithography-based molding processes were presented to fabricate poly N-isopropyl acrylamide (p-NIPAAm)-based hydrogel pillar array on a glass substrate. Au nanorods as light-induced heating elements were embedded within the hydrogel pillars, and near-infrared (NIR) light was used to modulate temperature in a local area. First, static responses of the micro-pillar array were characterized as a function of its temperature. It was shown that the hydrogel had a sensitive volume transition near its low critical solution temperature (LCST). Furthermore, we showed that LCST could be readily adjusted by utilizing copolymerizing with acrylamide (AAM). To demonstrate the feasibility of spatiotemporal temperature mapping and modulation using the presented pillar array, pulsed NIR light was illuminated on a local area of the hydrogel pillar array, and its responses were recorded. Dynamic temperature change in water was mapped based on the abrupt volume change characteristics of the hydrogel pillar, and its potential actuation using NIR light was successfully demonstrated. Considering that the structure can be arrayed in a two-dimensional pixel format with high spatial resolution and high sensitive temperature characteristics, the presented method and the device structure can have diverse applications to change and sense local temperatures in liquid. This is particularly useful in biological systems, where their physiological temperature can be modulated and mapped with high spatial resolution.

Consumers' Neophobic and Variety-Seeking Tendency in Food Choices According to Their Fashion Involvement Status: An Exploratory Study of Korean Consumers.

With recent food innovation and technological advances, a considerable number of new food products are being developed and launched in the global food market, and various attempts have been made to collaborate between food and fashion businesses to achieve a competitive edge. Fashion and food are essential items in our daily lives, so people are intentionally and unintentionally exposed to consumption decisions regarding these two items on a regular basis. The objective of this study was to determine consumers' neophobic and variety-seeking tendencies in food choices according to their involvement in fashion-related choices. Internet surveys were conducted (n = 215), which included questionnaires regarding the food neophobia scale (FNS), the variety-seeking scale (VARSEEK), and the fashion involvement scale (FIS), along with demographic-related questions. A negative correlation was observed between the FNS and FIS (r = -0.735, p < 0.0001), suggesting that consumers who are highly involved in fashion product choices have neophobic tendencies. A positive correlation was observed between VARSEEK and FIS scores (r = 0.353, p < 0.0001), as was expected from FNS and FIS results. No significant differences in demographic characteristics between those with high and low FIS scores were observed, suggesting that other factors may have influenced these results.

Ca2+-Permeable TRPV1 Receptor Mediates Neuroprotective Effects in a Mouse Model of Alzheimer's Disease via BDNF/CREB Signaling Pathway.

Transient receptor potential vanilloid 1 (TRPV1) protein is a Ca2+-permeable non-selective cation channel known for its pain modulation pathway. In a previous study, it was discovered that a triple-transgenic Alzheimer's disease (AD) mouse model (3xTg-AD+/+) has anti-AD effects. The expression of proteins in the brain-derived neurotrophic factor (BDNF)/cAMP response element binding protein (CREB) pathway in a 3xTg-AD/TRPV1 transgenic mice model was investigated to better understand the AD regulatory effect of TRPV1 deficiency. The results show that TRPV1 deficiency leads to CREB activation by increasing BDNF levels and promoting phosphorylation of tyrosine receptor kinase B (TrkB), extracellular signal-regulated kinase (ERK), protein kinase B (Akt), and CREB in the hippocampus. Additionally, TRPV1 deficiency-induced CREB activation increases the antiapoptotic factor B-cell lymphoma 2 (Bcl-2) gene, which consequently downregulates Bcl-2-associated X (Bax) expression and decreases cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP), which leads to the prevention of hippocampal apoptosis. In conclusion, TRPV1 deficiency exhibits neuroprotective effects by preventing apoptosis through the BDNF/CREB signal transduction pathway in the hippocampus of 3xTg-AD mice.

Effects of Caffeine Intake on Cardiopulmonary Variables and QT Interval after a Moderate-Intensity Aerobic Exercise in Healthy Adults: A Randomized Controlled Trial.

Caffeine is considered a widely consumed natural and legal psychoactive stimulant with several effects on the body. The present study attempted to investigate the effects of caffeine consumed before and after a physical exercise on cardiovascular and cardiorespiratory functions in healthy adults. 36 healthy adult males were recruited and randomly allocated to one of the three (3) groups: group I (exercise without caffeine consumption), group II (caffeine beverage intake before exercise), and group III (caffeine beverage intake immediately after exercise). The heart rate (HR), QTc interval, blood pressure (BP), respiratory rate (RR), oxygen consumption (VO2), and carbon dioxide emission (VCO2) were measured at 0, 5, 10, and 15 min after the exercise. We observed a significant difference in all measured outcomes during the different recovery times in all the groups (p < 0.05). HR, RR, SBP, VO2, and VCO2 gradually decreased with time, DBP contrarily increased with time, and the QTc showed an irregular pattern. We can affirm that ingestion of caffeine before and after moderate aerobic exercise slows down the parasympathetic stimulation, heart rate recovery, and the recovery of HR and QTc with no major effects on BP, RR, VO2, and VCO2 in healthy adult men.

Predicting Successes and Failures of Clinical Trials With Outer Product-Based Convolutional Neural Network.

Despite several improvements in the drug development pipeline over the past decade, drug failures due to unexpected adverse effects have rapidly increased at all stages of clinical trials. To improve the success rate of clinical trials, it is necessary to identify potential loser drug candidates that may fail at clinical trials. Therefore, we need to develop reliable models for predicting the outcomes of clinical trials of drug candidates, which have the potential to guide the drug discovery process. In this study, we propose an outer product-based convolutional neural network (OPCNN) model which integrates effectively chemical features of drugs and target-based features. The validation results via 10-fold cross-validations on the dataset used for a data-driven approach PrOCTOR proved that our OPCNN model performs quite well in terms of accuracy, F1-score, Matthews correlation coefficient (MCC), precision, recall, area under the curve (AUC) of the receiver operating characteristic, and area under the precision-recall curve (AUPRC). In particular, the proposed OPCNN model showed the best performance in terms of MCC, which is widely used in biomedicine as a performance metric and is a more reliable statistical measure. Through 10-fold cross-validation experiments, the accuracy of the OPCNN model is as high as 0.9758, F1 score is as high as 0.9868, the MCC reaches 0.8451, the precision is as high as 0.9889, the recall is as high as 0.9893, the AUC is as high as 0.9824, and the AUPRC is as high as 0.9979. The results proved that our OPCNN model shows significantly good prediction performance on outcomes of clinical trials and it can be quite helpful in early drug discovery.

Rapid photothermal actuation of light-addressable, arrayed hydrogel columns in a macroporous silicon membrane.

This paper presents rapid photothermal actuation of light-addressable, arrayed hydrogel columns in a macroporous silicon membrane. Au nanorods are incorporated into thermo-responsive p-NIPAAm hydrogel to utilize surface plasmon-induced local heating by near-infrared light. By measuring optical transmission through the fabricated membrane structure with Au nanorod embedded hydrogel, we have demonstrated that photothermal actuation of hydrogel can be done in two-dimensional, pixel-like configuration with high spatial and temporal resolutions. Benefiting from the hydrogel volume confinement within micron-sized pores, we have achieved sub-second response time of hydrogel photothermal actuation and its repeatable photothermal actuation on highly localized illuminated area. Considering that each hydrogel column is confined within each pore and different wavelength of light can be used to induce photothermal actuation of hydrogel's deswelling characteristics by modifying physical dimensions of Au nanorods, it has a potential for optically-addressable, multiplexed drug release systems with rapid response time.

Independent component analysis of E. coli's transcriptome reveals the cellular processes that respond to heterologous gene expression.

Achieving the predictable expression of heterologous genes in a production host has proven difficult. Each heterologous gene expressed in the same host seems to elicit a different host response governed by unknown mechanisms. Historically, most studies have approached this challenge by manipulating the properties of the heterologous gene through methods like codon optimization. Here we approach this challenge from the host side. We express a set of 45 heterologous genes in the same Escherichia coli strain, using the same expression system and culture conditions. We collect a comprehensive RNAseq set to characterize the host's transcriptional response. Independent Component Analysis of the RNAseq data set reveals independently modulated gene sets (iModulons) that characterize the host response to heterologous gene expression. We relate 55% of variation of the host response to: Fear vs Greed (16.5%), Metal Homeostasis (19.0%), Respiration (6.0%), Protein folding (4.5%), and Amino acid and nucleotide biosynthesis (9.0%). If these responses can be controlled, then the success rate with predicting heterologous gene expression should increase.

Dieckol, a Major Marine Polyphenol, Enhances Non-Rapid Eye Movement Sleep in Mice via the GABAA-Benzodiazepine Receptor.

We had previously demonstrated that phlorotannins, which are marine polyphenols, enhance sleep in mice via the GABAA-benzodiazepine (BZD) receptor. Among the constituents of phlorotannin, dieckol is a major marine polyphenol from the brown alga Ecklonia cava. Although phlorotannins are known to exert hypnotic effects, the sleep-enhancing effect of dieckol has not yet been determined. We evaluated the effect of dieckol on sleep-wake state of mice by analyzing electroencephalograms (EEGs) and electromyograms. Flumazenil, a GABAA-BZD antagonist, was used to investigate the molecular mechanism underlying the effects of dieckol on sleep. The polygraphic recordings and corresponding hypnograms revealed that dieckol accelerated the initiation of non-rapid eye movement sleep (NREMS); it shortened sleep latency and increased NREMS duration. According to the change in time-course, dieckol showed sleep-enhancing effects by increasing the amount of NREMS and decreasing wakefulness during the same hours. Additionally, sleep quality was evaluated by analyzing the EEG power density, and dieckol was found to not affect sleep intensity while zolpidem was found to reduce it. Finally, we treated mice with zolpidem or dieckol in combination with flumazenil and found the latter to inhibit the sleep-enhancing effect of dieckol and zolpidem, thereby indicating that dieckol exerts sleep-enhancing effects by activating the GABAA-BZD receptor, similar to zolpidem. These results implied that dieckol can be used as a promising herbal sleep aid with minimal side effects, unlike the existing hypnotics.

Fast thermoresponsive optical membrane using hydrogels embedded in macroporous silicon.

We have fabricated a temperature-sensitive hydrogel through copolymerization of N-isopropylacrylamide (NIPAAm) and Acrylamide (AAm) inside a macroporous silicon structure and demonstrated fast thermal response compared to its bulk structure. The presented method allows physical arrangement of micro-sized hydrogels within a predefined arrayed structure. Static and dynamic temperature responses of the fabricated structure are successfully demonstrated through optical transmission measurement. The measured temporal response reveals that presented structure can allow fast response time of the implemented hydrogels. Furthermore, spatial thermo-distribution pattern can be observed through pixel-like, arrayed macropores, which indicates a potential for addressing individual or single-channel hydrogel sensors or actuators through temperature stimulation.

Optical and Acoustic Sensor-Based 3D Ball Motion Estimation for Ball Sport Simulators †.

Estimation of the motion of ball-shaped objects is essential for the operation of ball sport simulators. In this paper, we propose an estimation system for 3D ball motion, including speed and angle of projection, by using acoustic vector and infrared (IR) scanning sensors. Our system is comprised of three steps to estimate a ball motion: sound-based ball firing detection, sound source localization, and IR scanning for motion analysis. First, an impulsive sound classification based on the mel-frequency cepstrum and feed-forward neural network is introduced to detect the ball launch sound. An impulsive sound source localization using a 2D microelectromechanical system (MEMS) microphones and delay-and-sum beamforming is presented to estimate the firing position. The time and position of a ball in 3D space is determined from a high-speed infrared scanning method. Our experimental results demonstrate that the estimation of ball motion based on sound allows a wider activity area than similar camera-based methods. Thus, it can be practically applied to various simulations in sports such as soccer and baseball.

Comparative study of macroporous silicon-based photovoltaic characteristics using indium tin oxide-silicon and pn-silicon junction based devices.

We report highly ordered macroporous silicon (Si)-based photovoltaic characteristics using indium tin oxide (ITO)/n-Si and pn-Si junction-based devices. The detailed fabrication processes including new controlled ITO etching are presented. Theoretical device simulations are performed to understand the presented device structures and propose an optimum device design based on processing limitations. The performance of ITO/n-Si junction devices directly depends on the conformal ITO coating along the pore surface. While pn-Si junction device requires additional doping step, the device can overcome the limitation of ITO conformal coating, especially for a device with high-aspect-ratio macropore structures. Experimental results also support the simulation analysis. The three-dimensional structural properties of well-defined macroporous Si coupled with the formation of photovoltaic devices are attractive for multi-functional applications.

Elastomeric Polymer Resonant Waveguide Grating based Pressure Sensor.

In this paper, we demonstrate an elastomeric polymer resonant waveguide grating structure to be used as a pressure sensor. The applied pressure is measured by optical resonance spectrum peak shift. The sensitivity - as high as 86.74pm/psi or 12.58pm/kPa - has been experimentally obtained from a fabricated sensor. Potentially, the sensitivity of the demonstrated sensor can be tuned to different pressure ranges by the choices of elastic properties and layer thicknesses of the waveguide and cladding layers. The simulation results agree well with experimental results and indicate that the dominant effect on the sensor is the change of grating period when external pressure is applied. Based on the two-dimensional planar structure, the demonstrated sensor can be used to measure applied surface pressure optically, which has potential applications for optical ultrasound imaging and pressure wave detection/mapping.

An acousto-optic sensor based on resonance grating waveguide structure.

This paper presents an acousto-optic (AO) sensor based on resonance grating waveguide structure. The sensor is fabricated using elastic polymer materials to achieve a good sensitivity to ultrasound pressure waves. Ultrasound pressure waves modify the structural parameters of the sensor and result in the optical resonance shift of the sensor. This converts into a light intensity modulation. A commercial ultrasound transducer at 20 MHz is used to characterize a fabricated sensor and detection sensitivity at different optical source wavelength within a resonance spectrum is investigated. Practical use of the sensor at a fixed optical source wavelength is presented. Ultimately, the geometry of the planar sensor structure is suitable for two-dimensional, optical pressure imaging applications such as pressure wave detection and mapping, and ultrasound imaging.

Polymer waveguide grating sensor integrated with a thin-film photodetector.

This paper presents a planar waveguide grating sensor integrated with a photodetector (PD) for on-chip optical sensing systems which are suitable for diagnostics in the field and in-situ measurements. III-V semiconductor-based thin-film PD is integrated with a polymer based waveguide grating device on a silicon platform. The fabricated optical sensor successfully discriminates optical spectral characteristics of the polymer waveguide grating from the on-chip PD. In addition, its potential use as a refractive index sensor is demonstrated. Based on a planar waveguide structure, the demonstrated sensor chip may incorporate multiple grating waveguide sensing regions with their own optical detection PDs. In addition, the demonstrated processing is based on a post-integration process which is compatible with silicon complementary metal-oxide semiconductor (CMOS) electronics. Potentially, this leads a compact, chip-scale optical sensing system which can monitor multiple physical parameters simultaneously without need for external signal processing.

Butyrate production in engineered Escherichia coli with synthetic scaffolds.

Butyrate pathway was constructed in recombinant Escherichia coli using the genes from Clostridium acetobutylicum and Treponema denticola. However, the pathway constructed from exogenous enzymes did not efficiently convert carbon flux to butyrate. Three steps of the productivity enhancement were attempted in this study. First, pathway engineering to delete metabolic pathways to by-products successfully improved the butyrate production. Second, synthetic scaffold protein that spatially co-localizes enzymes was introduced to improve the efficiency of the heterologous pathway enzymes, resulting in threefold improvement in butyrate production. Finally, further optimizations of inducer concentrations and pH adjustment were tried. The final titer of butyrate was 4.3 and 7.2 g/L under batch and fed-batch cultivation, respectively. This study demonstrated the importance of synthetic scaffold protein as a useful tool for optimization of heterologous butyrate pathway in E. coli.

Porous poly(lactic-co-glycolic acid) microsphere as cell culture substrate and cell transplantation vehicle for adipose tissue engineering.

Tissue engineering often requires ex vivo cell expansion to obtain a large number of transplantable cells. However, the trypsinization process used to harvest ex vivo expanded cells for transplantation interrupts interactions between cultured cells and their extracellular matrices, facilitating apoptosis and consequently limiting the therapeutic efficacy of the transplanted cells. In the present study, open macroporous poly(lactic-co-glycolic acid) (PLGA) microspheres were used as a cell culture substrate to expand human adipose-derived stromal cells (ASCs) ex vivo and as a cell transplantation vehicle for adipose tissue engineering, thus avoiding the trypsinization necessary for transplantation of ex vivo expanded cells. Human ASCs cultured on macroporous PLGA microspheres in stirred suspension bioreactors expanded 3.8-fold over 7 days and differentiated into an adipogenic lineage. The apoptotic activity of ASCs cultured on microspheres was significantly lower than that of trypsinized ASCs. ASCs cultured on microspheres survived much better than trypsinized ASCs upon transplantation. The implantation of ASCs cultured on microspheres resulted in much more extensive adipose tissue formation than the implantation of ASCs cultured on plates, trypsinized, and subsequently mixed with microspheres. Ex vivo cell expansion and transplantation using this system would improve the therapeutic efficacy of cells over the current methods used for tissue engineering.

Apatite-coated poly(lactic-co-glycolic acid) microspheres as an injectable scaffold for bone tissue engineering.

Biodegradable polymer/ceramic composite scaffold could overcome limitations of biodegradable polymers or ceramics for bone regeneration. Injectable scaffold has raised great interest for bone regeneration in vivo, since it allows one for easy filling of irregularly shaped bone defects and implantation of osteogenic cells through minimally invasive surgical procedures The purpose of this study was to determine whether apatite-coated poly(lactic-co-glycolic acid) (PLGA) microspheres could be used as an injectable scaffold to regenerate bone in vivo. Apatite-coated PLGA microspheres were fabricated by incubating PLGA microspheres in simulated body fluid. The apatite that coated the PLGA microsphere surfaces was similar to apatite in natural bone, as demonstrated by scanning electron microscopy, X-ray diffraction spectra, energy-dispersive spectroscopy, and Fourier transformed-infrared spectroscopy analyses. Rat osteoblasts were mixed with apatite-coated PLGA microspheres and injected immediately into subcutaneous sites of athymic mice. Osteoblast transplantation with plain PLGA microspheres served as a control. Histological analysis of the implants at 6 weeks with hematoxylin and eosin staining, Masson's trichrome staining, and von Kossa staining revealed much better regeneration of bone in the apatite-coated PLGA microsphere group than the plain PLGA microsphere group. The new bone formation area and the calcium content of the implants were significantly higher in the apatite-coated PLGA microsphere group than in the plain PLGA microsphere group. This study demonstrates the feasibility of using apatite-coated PLGA microspheres as an injectable scaffold for in vivo bone tissue engineering. This scaffold may be useful for bone regeneration through minimally invasive surgical procedures in orthopedic applications.

Nanosphere-mediated delivery of vascular endothelial growth factor gene for therapeutic angiogenesis in mouse ischemic limbs.

Polymeric nanosphere-mediated gene delivery may sustain the duration of plasmid DNA (pDNA) administration. In this study, poly(lactic-co-glycolic acid) (PLGA) nanospheres were evaluated as a gene carrier. The pDNA-loaded PLGA nanospheres were formulated with high encapsulation efficiency (87%). The nanospheres sustained release of pDNA for 11 days. The released pDNA maintained its structural and functional integrity. Furthermore, the PLGA nanospheres showed lower cytotoxicity than polyethylenimine (PEI) in vitro and in vivo. The nanospheres with vascular endothelial growth factor (VEGF) gene were injected into skeletal muscle of ischemic limb model, and gene expression mediated by the PLGA nanospheres with VEGF gene was compared to that of PEI/pDNA or naked pDNA in vivo. PLGA nanosphere/pDNA had significantly higher VEGF expression levels in comparison to PEI/pDNA and naked pDNA at 12 days after administration. In addition, gene therapy using PLGA nanospheres resulted in more extensive neovascularization at ischemic sites than both naked pDNA and PEI/pDNA. These results indicated that PLGA nanosphere might be useful as a potential carrier for skeletal muscle gene delivery applications.

Integrated thin film InGaAsP laser and 1 x 4 polymer multimode interference splitter on silicon.

We report on a thin film InGaAsP laser integrated with a 1 x 4 polymer multimode interference (MMI) splitter on a silicon substrate for planar optical signal distribution. The thin film laser had a threshold current of 40 mA and was endfire coupled to the integrated passive polymer MMI splitter, and the optical signal from the laser was distributed to the four output waveguides of the MMI coupler. The measured loss of the MMI splitter was 0.79 dB. The normalized powers of the four MMI output ports in the integrated system were measured to be 0.823, 0.978, 0.852, and 1.