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Recently, CMOS-based artificial neurons have successfully implemented neuron functions such as integrate and fire (IF) or leaky integrate and fire (LIF). In general, CMOS-based artificial neurons use capacitors to implement integration function of neuron. In this case, required RC time constant is about few milliseconds. And it requires large area of capacitor more than 1000F2. Therefore, it is necessary to develop capacitor-less artificial neuron to achieve high neuronal density. In this works, we implemented the integration function of neurons using CBRAM instead of capacitors. For the neuron device, CuTe/TiO2/TiN CBRAM cell was fabricated as shown in figure 1a. The neuron device has W bottom electrode with ~113 nm2 pattern size and 10 nm-thick TiO2 layer, and 200 nm-thick CuTe top electrode with 60 μm2 size. The TiO2-based CBRAM showed a typical bi-stable I-V curve as shown in figure 1b. The CBRAM cells showed negative differential resistance (NDR) during reset process. And it showed integrate characteristic when consecutive negative voltage pulse was induced to top electrode of the CBRAM cell. Figure 1c shows integrate characteristic of TiO2-based CBRAM cell. As shown in figure 1c, as the voltage pulse is applied, current gradually decreases. Also as amplitude of voltage pulse increased, the change of current became greater. Because the area of the CBRAM cell is only 4F2, it is expected that area of artificial neuron can be significantly reduced by replacing conventional capacitor based neuron. We will present how the CBRAM cell can be used to implement artificial neuron. Figure 1

Resistive random access memory (ReRAM) is one of the most promising candidates for the next-generation memory due to its simple structure, high switching speed and low power consumption [1]. Recently, there has been large interests in using carbon-baed material as solid electrolyte to overcome the limit of conventional metal-oxide memory. It has remarkable advantages over past metal-oxide memory such as high memory margin (Ion/Ioff > 100) and fast switching speed (20~50ns) [2]. However, the requirement of forming process to activate resisitive switching operation is one of the critical issues. Forming process may degrade the device switching characteristic and is not desirable for circuit design. In this study, forming-free characteristic of a-COx (amorphous carbon oxide) based ReRAM was observed by controlling the Cu-filament shape. To accurately control the Cu-atom concentration profile, insertion of Cu thin film was carried out in several ways. The first device, named A, was fabricated with the common ReRAM structure of Pt / Cu-doped a-COx / W. The second device, named B, was vertically stacked with the strcutrue of Pt / a-COx / Cu-doped a-COx / W. The third device, named C, was vertically stacked with the strcutrue of Pt / Cu-doped a-COx / a-COx / Cu-doped a-COx / W. The device was fabricated on W bottom electrode wafer patterned from 34 nm to 1921 nm by photo lithography process. The a-COx and other metals were deposited using dc magnetron sputter (PVD method). After the fabrication, the Cu-atom concentration profile was carefully examined using SIMS analysis to understand the correlation between forming-free chracteristic and Cu-filament shape. Forming-free characteristic device presented identical forming and set voltage of -0.85 V. Moreover, the result indicated that the high resistance state current of 2.41-7 A at 0.1 V, low resistance state current of 5.98-5 A at 0.1 V and the memory window margin (Ion/Ioff) of 2.48×102. In our study, we present that the precise design of the Cu-atom concentration profile of a-COx based ReRAM is the significant key to achieve the forming-free and stable non-volatile memory characteristic. [1] Daniele Ielmini, Semicond. Sci. Technol. 31 (2016) 063002 [2] Claudia A. Santini et al, NAT COMMUN, 6:8600 (2015) * This material is based upon work supported by the Ministry of Trade, Industry & Energy(MOTIE, Korea) under Industrial Technology Innovation Program (10068055). Figure 1

The main objective of this study was to determine the central mechanisms involved in suppression of thermal sweating after seasonal acclimatization (SA) during passive heating (immersing the legs in 43 °C hot water for 30 min). Testing was performed in July (before-SA) and August (after-SA) [25.2±2.2 °C, 73.9±10.3% relative humidity (RH), Cheonan (Chungnam,126° 52′N, 33.38′E), in the Republic of Korea. All experiments were carried out in an automated climatic chamber (25.0±0.5 °C and RH 60.0±3.00%). Twelve healthy men (height, 174.6±5.40 cm; weight, 65.4±5.71 kg; age, 22.7±2.90 yr) participated. The local sweat onset time was delayed in the after-SA compared to that in the before-SA (p

We developed a continuously porous scaffold with laminated matrix and bone-like microstructure by a multi-pass extrusion process. In this scaffold, tetragonal ZrO2, biphasic calcium phosphate and poly-caprolactone layers were arranged in a co-axially laminated unit cell with a channel in the center. The entire matrix phase had a laminated microstructure of alternate lamina of tetragonal ZrO2, biphasic calcium phosphate and poly-caprolactone—biphasic calcium phosphate with optimized designed thickness and channeled porosity. Each of the continuous pores was coaxially encircled by the poly-caprolactone—biphasic calcium phosphate layer, biphasic calcium phosphate layer and finally tetragonal ZrO2 layer, one after the other. Before extrusion, 5 vol% graphite powder was mixed with tetragonal ZrO2 to ensure pores in the outer layer and connectivity among the lamellas. The design strategy is aimed to incorporate a lamellar microstructure like the natural bone in the macro-scaled ceramic body to investigate the strengthening phenomenon and pave the way for fabricating complex microstructure of natural bone could be applied for whole bone replacement. The final fabricated scaffold had a compressive strength of 12.7 MPa and porosity of 78 vol% with excellent cell viability, cell attachment and osteocalcin and collagen expression from cultured MG63 cells on scaffold.

We assessed the effect of caffeine on sudomotor activity and sweating sensitivity during physical loading. Both physiological responses could occur due to energy expenditure. Subjects were 13 athletically trained males (22.1 ± 3.7 years old, 174.2 ± 5.4 cm tall, and weighing 70.9 ± 4.6 kg, with maximal oxygen consumption [VO(2)max] of 53.6 ± 4.4 mL/kg/minute). The study involved a within-subject, random, crossover design. Tests were performed following the ingestion of 3 mg/kg caffeine. The physical loading involved running for 30 minutes at 60% VO(2)max (24.0 ± 0.5°C, 40 ± 3.0% relative humidity). Tympanic temperature (TYMP) was significantly higher in the caffeine-consuming group (Caffe-I) at pre-exercise (40 minutes after caffeine intake and immediately before running) (P

This study investigated the effects of oligonol intake on cortisol, interleukin (IL)-1β, and IL-6 concentrations in the serum as well as body temperature after leg immersion into hot water. Thirteen healthy male volunteers participated in this study. Each subject received oligonol (100 mg) before leg immersion into hot water. Skin and tympanic temperatures were measured and mean body temperatures were calculated. Serum concentrations of cortisol, IL-1β, and IL-6 were measured during and after leg immersion. Individuals who received oligonol had significantly decreased cortisol concentrations and serum levels of IL-1β and IL-6 compared to ones who did not receive oligonol. In addition, skin, tympanic, and mean body temperatures of oligonol group were maintained at lower degree overall recovery period compared with placebo group. These results suggest that oral oligonol intake before hot water immersion had a significant effect on inhibition of pyrogenic cytokine response and thermal suppression in healthy young men.

In this work, Simvastatin (SIM) loaded porous poly(lactic-co-glycolic acid) (PLGA) microspheres were fabricated using the W/O/W1/W2 double emulsion and solvent evaporation method. The optimal conditions for fabricating porous PLGA microspheres were determined to be 20% distilled water (v/v), 10% PLGA (m/v), and a 4:1 ratio of internal polyvinyl alcohol (PVA) to dichloromethane (DCM). The pores size distribution of porous PLGA microspheres was varied from 0.01 to 40 μm, while their particle displayed a bimodal size distribution that had two diameter peaks at around 100 μm and 500 μm. The SIM encapsulation efficacy was found to be very high with a yield near 80% and the porous PLGA microspheres showed the excellent biocompatibility. In addition, the drug release profile was found to be significantly different from a temporal basis. Base on the combined results of this study, SIM loaded PLGA microspheres holds great promise for use in biomedical applications, especially in drug delivery system or tissue regeneration.

This study measured caffeine-induced changes in activated sweat gland density (ASGD) and fat oxidation using a randomized crossover design with 10 healthy volunteers given caffeine (Caffe-I, 3 mg/kg ingested 30 min before experiment) and non-caffeine (No-Caff). Subjects were 173.0±3.2 cm in height, 72.5±4.3 kg in weight, and 21.5±2.5 years in age. All experiments were performed in an automated climate chamber (24.0±0.5°C, relative humidity 50±3%, air velocity less than 1 m/sec) between 2–5 p.m. The ASGD on the chest, upper arm, upper back, and lower back were measured (after 30 min running at 60% VO2max), and blood samples were taken (at 40 min before, immediately before and after 30 min running). Activated sweat gland density levels were higher in Caffe-I (Chest p

Resistive random access memory (ReRAM) is one of the most promising candidates for the next-generation memory due to its simple structure, high switching speed and low power consumption [1]. Despite of such advantages, its non-volatile characteristic strongly depends on memory cell size. To overcome the weakness, conductive bridging random access memory (CBRAM) cells have been researched as an alternative to oxygen-vacancy type ReRAM cells since CBRAM cells showed independence of non-volatile memory characteristics on the memory cell size [2]. However, CBRAM cells usually require a forming process to produce metal filaments in the solid-electrolyte before memory operation. It had a negative effect on the device since it reflects a high-power consumption. Thus, in this work, Cu2O-based CBRAM cells with forming-free characteristic were presented. In addition, we mainly focused on understanding the dependency of forming-free process on annealing temperature. To confirm the presence of forming process, the resistive switching device was fabricated on a Pt-bottom electrode (BE) with a 250nm via-hole pattern, and annealed at the temperature of as-sputtered, 150, 250 and 300 ˚C. As shown in Fig. 1(a) and 1(b), as-sputtered and 150 ˚C post annealing CBRAM cells demonstrated forming-free characteristic. However, reset process was not effectively work. For the case of 300 ˚C post annealing CBRAM cell, it required forming process as shown in Figure. 1(d). CBRAM cell with 250 ˚C post annealing demonstrated both bi-stable I-V characteristic and forming free characteristic. To understand the mechanism of the forming-free process at 250 ˚C post annealing, EDS line scanning/mapping were carried out on the CBRAM cells annealed at 150, 250, 300 and 400 ˚C repectively (Fig.2 (a)-(d)). According to the EDS analysis, the diffusion amount of Ag in the Cu2O layer decreases as the annealing temperature increases. This tendency can be attributed to the decrease in the number of metal vacancies sites. In the saturated case, as shown in Fig. 2(a) and 2(b), the reset process did not effectively work due to the excessive density of VCu 2- leaving not enough room for breaking the filament. In the optimal case, as shown in Fig. 2(c), forming-free characteristic and both set/reset process worked successfully due to the optimal gap between the concentrated area of Ag and the bottom electrode. In the deficient case, as shown in Fig. 2(d), the forming process was required due to the low density of VCu 2- in solid-electrolyte layer and the high gap between the concentrated area of Ag and bottom electrode. In our study, we report the annealing temperature (250 ˚C is the optimal condition in this study) is the significant key to achieve the forming-free and stable non-volatile characteristics via controlling the concentration of negatively charged Cu vacancies, where Ag ions can diffuse through. [1] Daniele Ielmini, Semicond. Sci. Technol. 31 (2016) 063002 [2] Ilia Valov, J. Phys. D: Appl. Phys. 46 (2013) 074005 This material is based upon work supported by the Ministry of Trade, Industry & Energy(MOTIE, Korea) under Industrial Technology Innovation Program (10068055). Figure 1

This study investigated the effects of Oligonol intake on cortisol, interleukin (IL)-1beta, and IL-6 concentrations in the serum at rest and after physical exercise loading. Nineteen healthy sedentary male volunteers participated in this study. The physical characteristics of the subjects were: a mean height of 174.2 +/- 2.7 cm, a mean weight of 74.8 +/- 3.6 kg and a mean age of 22.8 +/- 1.3 years. Each subject received 0.5 L water with Oligonol (100 mg/day) (n = 10) or a placebo (n = 9) daily for four weeks. The body composition, the white blood cell (WBC) and differential counts as well as the serum cortisol, IL-1beta, and IL-6 concentrations were measured before and after Oligonol intake. The cortisol concentration and serum levels of IL-1beta and IL-6 after Oligonol intake were significantly decreased compared to before treatment (P0.01, respectively). In addition, the rate of increase of these factors after exercise was decreased compared to the placebo group. There was no change in the WBC and differential cell counts. These results suggest that oral Oligonol intake for four weeks had a significant effect on inhibition of inflammatory markers in healthy young men.

This study investigated the anti-inflammatory effects of Pellinus linteus (PL) extract supplementation in healthy young men. The subjects were 18 healthy young males 20 years of age that were given 1.5 L of 0.12% PL extract orally (n=8) or a placebo (control group, n=10) daily for 4 weeks. The body composition, the white blood cell (WBC) count and differential as well as the serum cortisol, interleukin (IL)-1β, and IL-6 concentrations were measured before and after the supplementation. Serum concentrations of cortisol and IL-1β at rest after oral supplementation were significantly decreased compared to before treatment (p

Calcium phosphate bone substitutes are widely used for providing support for the in-growth of hard tissue in various medical applications (e.g., dental, orthopedic). Recently, research involving bone substitutes with interconnected open pore structures has focused on improving the mechanical properties of the substitutes and modifying their surfaces with proteins (e.g., collagen, bone morphogenetic protein) to induce early bone formation. In particular, it is highly desirable to develop a functional gradient-structured bone substitute that has the potential to control the bioresoption rate. A porous BCP scaffold was fabricated by the sponge replica method using a PU sponge. The sponge was dip coated three times followed by oven drying, burning out, and microwave sintering. Several approaches were used to fabricate a functional gradient scaffold. TCP was synthesized using the sol-gel process, and it infiltrated into the pore channel that formed after the burning out of the PU sponge. X-ray diffraction analysis characterized the phase identification of the BCP scaffold. Microstructures of the composites were observed using scanning electron microscopy.

Natives of the tropics are able to tolerate high ambient temperatures. This results from their long-term residence in hot and often humid tropical climates. This study was designed to compare the peripheral mechanisms of thermal sweating in tropical natives with that of their temperate counterparts. Fifty-five healthy male subjects including 20 native Koreans who live in the temperate Korean climate (Temperate-N) and 35 native tropical Malaysian men that have lived all of their lives in Malaysia (Tropical-N) were enrolled in this study after providing written informed consent to participate. Quantitative sudomotor axon reflex testing after iontophoresis (2 mA for 5 min) with 10% acetylcholine (ACh) was used to determine directly activated (DIR) and axon reflex-mediated (AXR) sweating during ACh iontophoresis. The sweat rate, activated sweat gland density, sweat gland output per single gland activated, and oral and skin temperature changes were measured. The sweat onset time of AXR (nicotinic-receptor-mediated) was 56 s shorter in the Temperate-N than in the Tropical-N subjects (P0.0001). The nicotinic-receptor-mediated sweating activity AXR (1), and the muscarinic-receptor-mediated sweating activity DIR, in terms of sweat volume, were 103% and 59% higher in the Temperate-N compared to the Tropical-N subjects (P0.0001). The Temperate-N group also had a 17.8% (P0.0001) higher active sweat gland density, 35.4% higher sweat output per gland, 0.24 degrees C higher resting oral temperature, and 0.62 degrees C higher resting forearm skin temperature compared to the Tropical-N subjects (P0.01). ACh iontophoresis did not influence oral temperature, but increased skin temperature near where the ACh was administered, in both groups. These results suggest that suppressed thermal sweating in the Tropical-N subjects was, at least in part, due to suppressed sweat gland sensitivity to ACh through both recruitment of active sweat glands and the sweat gland output per each gland. This physiological trait guarantees a more economical use of body fluids, thus ensuring more efficient protection against heat stress.

Various calcium phosphate bioceramics are distinguished by their excellent biocompatibility and osteoconductivity. Especially, the exceptional biodegradability of β-TCP makes it a bone graft substitute of choice in many clinical applications. The activation of osteoclasts, differentiated from macrophage precursor cells, trigger a cell-mediated resorption mechanism that renders β-TCP biodegradable. Based on this evidence, we studied the biodegradation process of granular-type β-TCP bone graft substitute through in vitro and in vivo studies. Raw 264.7 cells treated with RANKL and M-CSF differentiated into osteoclasts with macrophage-like properties, as observed with TRAP stain. These osteoclasts were cultured with β-TCP nano powders synthesized by microwaveassisted process. We confirmed the phagocytosis of osteoclasts by observing β-TCP particles in their phagosomes via electron microscopy. No damage to the osteoclasts during phagocytosis was observed, nor did the β-TCP powders show any sign of cytotoxicity. We also observed the histological changes in subcutaneous tissues of rats implanted with granule-type β-TCP synthesized by fibrous monolithic process. The β-TCP bone graft substitute was well surrounded with fibrous tissue, and 4 months after implantation, 60% of its mass had been biodegraded. Also, histological findings via H&E stain showed a higher level of infiltration of lymphocytes as well as macrophages around the granule-type β-TCP. From the results, we have concluded that macrophages play an important role in the biodegradation process of β-TCP bone graft substitutes.

Recent studies showed that tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), as well as high-sensitive C-reactive protein (hsCRP) levels are predictive factors of cardiovascular risk. However, the effect of cardiac rehabilitation (CR) intervention in coronary artery disease (CAD) patients on these factors is not known. The aim of this study was to evaluate the effects of CR and exercise on hsCRP and inflammatory cytokine levels in patients with CAD after percutaneous coronary intervention (PCI). CAD patients who underwent PCI were divided into a CR and exercise group (CRE, n = 29) or a control group (CON, n = 10). CR and exercise consisted of 6 weeks supervised exercise training and 8 weeks home-based, self-managed exercise. Compared to pre-experimental levels, TNF-alpha (by 20.4%; p = 0.006) and IL-6 (by 49.0%; p < 0.0001), as well as hsCRP (by 59.4%; p < 0.0001), were markedly decreased after CR and exercise in CAD patients but not in control group, except for IL-6 (by 41.6%; p = 0.001). However, there was no significant alteration of adiposity-related variables such as BMI, percent body fat, and waist circumferences, in both groups. We suggest that CR and exercise in CAD patients after PCI induce significant reduction in hsCRP and inflammatory cytokines (TNF-alpha and IL-6), and marked increase in exercise tolerance and capacity.

Tropical natives possess heat tolerance due to the ability to off-load endogenous and exogenous heat efficiently using a minimum amount of sweat. On the other hand, exposure of temperate natives to heat results in exaggerated production of sweat, of which part is lost by dripping and, thus, not available for evaporation. How sweating is modified in natives of temperate climate zones by prolonged residence in the tropics is not well-understood. The aim of this study was to investigate possible changes in the peripheral sweating mechanisms. Sweating responses to iontophoretically applied acetylcholine (ACh) were compared between Japanese subjects having either permanently resided in Japan (Japan resident Japanese, JRJ) or having stayed in the tropics for 2 years or longer (Tropics resident Japanese, TRJ). Quantitative sudomotor axon reflex tests by iontophoresis of ACh (10%, 2 mA for 5 min) were applied to determine directly activated (DIR) and axon reflex-mediated sweating during [AXR(1)] and after [AXR(2)] ACh iontophoresis. The sweat onset time of AXR(1) was 0.6 min shorter in JRJ than in TRJ (P

Accumulating evidence suggests that higher antibody titers to heat shock proteins (HSPs) are associated with the development and severity of atherosclerosis. The aim of this study was to evaluate the impact of cardiac rehabilitation therapy (CRT) or stain treatment (STT) or a combination of both (COM) on anti-HSP antibodies in patients with coronary artery disease (CAD) after percutaneous coronary intervention (PCI). Clinical evaluation of subjects was performed both at the commencement and completion of the 14 weeks of treatment. CRT consisted of a supervised 6 weeks of exercise following hospital discharge and 8 weeks of home stay exercise. Patients assigned to statin therapy were treated with 80 mg per day of fluvastatin. Blood samples from 39 patients were analyzed for antibodies to HSP60 and HSP70 by ELISA. Biochemical parameters, including lipids, high-sensitivity C reactive protein (hsCRP), and interleukin-6 (IL-6), were also analyzed. We found that CRT and COM reduced antibody titers to HSP60 and HSP70 in CAD patients (by 3.79 and 10.00% of anti-HSP60, and by 5.74 and 3.45% of anti-HSP70, respectively) but statin treatment reduced only antibody titers to HSP70 (by 3.83%). There was a significant correlation between antibody titers to HSP60 versus HSP70. Considering the fact that antibody titers to HSPs are associated with the autoimmune process in CAD, CRT and COM have greater effects on reduction in autoimmune reaction after PCI than statin treatment. This reduction was accompanied by greater improvements in blood biochemical variables, such as lipids, hsCRP, and IL-6 after CRT and COM.

A study was made to observe the association between the resistance to reinfection induced by irradiated metacercariae (MC) of Clonorchis sinensis and antigen specific Th1- and Th2-type cytokine productions in rats. Rats were infected with 20 MC of C. sinensis, previously exposed to a single dose of gamma irradiation, which varied from 0 to 100 Gy. All of them, single dose of 12 Gy showed higher IgG antibody titer with lowest worm recovery. Thus, 50 MC were used to challenge infection in rats previously infected with 20 MC irradiated at 12 Gy and the highest resistance to challenge infection was observed. The results of lymphocyte proliferation with specific antigen, ES Ag were shown no difference of proliferative responses as compared with primary and challenge infection at 12 Gy irradiation dose. In the case of cytokines production were observed that interferon (IFN-gamma) and interlukin (IL-2) were significantly enhanced, while IL-4 and IL-10 was almost unchanged to make comparison between primary and secondary infection at 12 Gy irradiation dose. In conclusion, the single dose of 12 Gy could be adopted for induction of the highest resistance to challenge infection. Up-regulation of Th1 type cytokines, IFN-gamma and IL-2 may be affected to develop vaccine by irradiated MC.

Tropical subjects regulate core temperature with less amount of sweat against heat compared to temperate subjects through long-term heat-acclimatization. The purpose of the study is to determine whether acclimatization in tropical subjects decay during a stay in temperate area. The aim of this study, therefore, was to investigate the possible changes in the peripheral sweating mechanisms. Local sweating response activated by acetylcholine (ACh) applied iontophoretically among Malaysians with varying duration of stay in Japan and Japanese resident subjects. Directly activated (DIR) and axon reflex (AXR)-mediated sweating during ACh iontophoresis were measured by capacitance hygrometer (quantitative sudomotor axon reflex test, QSART) QSART was performed in a thermoneutral condition (24±0.5 °C, 40±3% rh). The sweat onset-time after the current loading was 1.05 min shorter in Malaysian with long-term stay in Japan (MLJ) than in Malaysian, and the AXR(1), AXR(2) and DIR sweating in MLJ were larger than Malaysian. From these results, suppressed neuroglandular response to ACh was confirmed in Malaysians. It is suggested that long-term heat-acclimatization acquired in tropical subjects may decay after immigration to temperate area.

This study was designed to investigate the expression of heat shock protein 70 (HSP70), after acute moderate intensity exercise, in human peripheral blood leukocytes of trained runners and untrained controls. Ten male long-distance trained runners (TR) and untrained sedentary control subjects (SED) ran for 1 h at 70% of heart rate reserve (HRR). Basal HSP70 expression in TR was usually lower than that in SED, but basal HSP70 gene expression in TR was usually higher than that in SED. Although expression rates of exercise-induced HSP70 in both groups were similar, levels of HSP70 in SED were significantly higher than in TR. Significant increases in leukocytes, neutrophils, and lymphocytes after exercise were observed in both groups, but there were some differences between groups. We conclude that 1 h treadmill running at 70% HRR intensity is a sufficient stimulus to leukocytosis, neutrocytosis, lymphocytosis, and HSP70 proteins and gene expression in leukocytes. Adaptation to training was observed in TR.

This study investigated the exercise-induced synthesis and accumulation of heat shock protein 70 (HSP70) after progressive strenuous exercise in rat soleus, plantaris, and myocardium. Sprague-Dawley rats were randomly assigned to one of six groups, one control group and five exercise groups, divided by intensity and duration of exercise. Skeletal muscles and heart were dissected immediately after last performance. The levels of HSP70 were analyzed by western blotting using a specific polyclonal antibody. Basal levels of HSP70 in soleus were the highest, and then followed by the myocardium and plantaris, in turn. Progressive strenuous exercise increased accumulation of HSP70 gradually in all three tissues. There were differences in patterns of increase among three tissues.

Hyperthermia (HT) in combination with anticancer drugs (ACDs) had proven to more efficacious in various cancers, although efficacies vary according to chemotherapeutic compounds and cancer types. Presently there are few data that compares anticancer efficacies among ACDs under hyperthermic conditions. Therefore, we selected three commonly used ACDs (quercetin, verapamil and doxorubicin) and compared their antitumor effects when each was treated with 43°C HT exposure. Firstly, FM3A, a murine breast cancer cell line, was treated with each ACD for 1 h followed by 43°C exposure for additional 1 h, and examined the effects of: 1) each drug, 2) 43°C HT exposure, and 3) the combination of each drug and 43°C HT exposure for 1, 6 and 24 h. The determined overall effects on FM3A cells were arrested cell proliferation, clonogenic efficiency and apoptosis. Pre-treatment of FM3A cells to each ACD followed by 43°C HT exposure produced greater antitumor effects including suppressed cell proliferation, reduced clonogenic efficiency and increased apoptotic cell death, compared to ACD treatment or HT exposure alone. Apoptotic cell death occurred in a time-dependent manner. Among the ACDs, antitumor efficacies varied in the order of doxorubicin > verapamil > quercetin. It was concluded that heat exposure during ACD treatment of caner cells may be an important factor to get a better antitumor benefit, even though this benefit may differ from one drug to another.

Food allergy is an important and common health issue, and there is a need to identify and characterize the sensitizing mechanisms. One of the common causes of food allergy is ovalbumin (OVA), a dietary antigen from eggs. We hypothesized that OVA-induced food allergy in the gut involves the activation of the chemokine regulated on activation, normal T cell expressed and secreted (RANTES), which then recruits eosinophils to lesioned tissue. The purpose of this study was to clarify whether RANTES expression correlates with eosinophil infiltration in the gut of OVA-sensitized BALB/c mice in response to oral OVA challenge. BALB/c mice were immunized with OVA 1 microg and sensitized after 2 weeks by intragastric administration of OVA. Sensitization to the oral OVA challenge was analyzed by examining eosinophil infiltration into the gut tissue (immunohistochemistry), mucosal eosinophil cationic protein (ECP) concentration, and RANTES mRNA expression (reverse-transcriptase polymerase chain reaction and Southern blotting) at 3, 6, 12, and 24 h after the challenge. There was marked edema of the intestinal villi, and eosinophil infiltration to the lamina propria peaked at 6 h in OVA-sensitized mice. RANTES mRNA expression peaked at 3 h and 6 h and declined thereafter. The expression of RANTES mRNA in the allergic mice was much higher than in the nonallergic, normal, or unsensitized control mice. Tissue eosinophilia and intestinal ECP levels were significantly correlated with the RANTES mRNA level. We conclude that RANTES may play a central role in the pathogenesis of food-mediated gastrointestinal allergy.

An enzyme linked immunosorbent assay (ELISA) was used to study the correlation between the levels of IgG, IgM and IgE immunoglobulin isotypes and resistance to reinfection in rats during the first month of infection with Clonorchis sinensis. Rats were infected with Clonorchis sinensis (primary infection), and then treated with praziquantel on the 1st, 3rd, 7th, 14th and 28th day post infection (p.i.). To measure resistance, rats were re-infected with C. sinensis (secondary infection), 2 weeks after the treatment and worms were recovered 4 weeks later. During the primary infection, significantly increased levels of IgG isotype were observed on days 14 and 28 p.i. (P < 0.001) and IgM levels were significantly increased on 3rd and 28th day (P < 0.001). During the secondary infection, significantly increased levels of IgG isotype were found from 3rd to 28th day and IgE isotype on 7th and 14th day (P < 0.01) while significant levels of IgM were found on the 3rd and 28th day (P < 0.05). Furthermore, significant differences of worm numbers between infected and control group was found on the 14th and 28th day (P < 0.001). An inverse correlation betwee the IgG levels and the resistance to re-infection was also observed (r = -0.948, P = 0.004), indicating that the resistance to reinfection is highly associated with the levels of IgG during the early phase of infection, and then with the IgM and IgE.

Tropical subjects regulate core temperature with less amount of sweat against heat compared to temperate subjects through long-term heat-acclimatization. The purpose of the study is to determine whether acclimatization in tropical subjects decay during a stay in temperate area. Local sweating response activated by acetylcholine (ACh) applied iontophoretically among Malaysians (n=26) with varying duration of stay in Japan and Japanese residents subjects (J-R n=30). Based on their length of stay, Malaysian subjects were divided into three groups, group M-S (n=9) with a duration of stay oflto 12 months, M-M (n=7) with 13 to 36 months and M-L (n=10) with 37 to 72 months. ACh, the primary transmitter for sudomotor innervation, was iontophoretically administered on the forearm. Sweating response elicited directly (DIR) and indirectly via axon reflex (AXR) were evaluated by quantitative sudomotor axon reflex test. The onset-time of AXR was shortened with the longer duration of stay among Malaysian subjects (P

Resistive random access memories (ReRAMs) have been researched to replace current NAND flash memory due to non-volatile memory characteristics, low power consumption, high operation speed, and minimum 4F2 memory cell size[1]. However, to achieve high density of tera-bit level cells, it is needed to operate ReRAM cells with cross-point array structure which required selection device to limit the sneak current path in high-density ReRAM cells. Therefore, recently bi-directional selection devices with two-terminal structure such as ovonic threshold switching (OTS)[2], p-n-p type (PNP)[3], and mixed ionic electronic conduction (MIEC)[4] have been researched to suppress the sneak current path. In this work, we investigated the electrical features of the selection device with Cu-doped chalcogenide material to attain high non-linearity(>105), high on-state current(Ion )(>10 MA/cm2) and low off-state current(Ioff )(2) because Cu ions moved well by E-field and generated interstitials/vacancies acting as dopants. We fabricated the selection device of the structure of W / Cu-doped chalcogenide material / Pt by varying the pattern size of ranging 34 to 1,921 nm as shown in Fig.1. The device performance of Ion , Ioff , threshold voltage(VT ), and non-linearity(Ion @Von/Ioff @1/2Von ) was characterized. The Cu-doped chalcogenide material layer was deposited by RF magnetron co-sputtering on W bottom electrode patterned by photo lithography process. Then, Pt top electrode was deposited by DC magnetron sputtering. The selection device with Cu-doped chalcogenide material demonstrated threshold voltage of ~1.0 V, low Ioff of < 3.66 mA/cm2, Ion of > 1.82 A/cm2, and non-linearity of > 500 as shown in Fig.2. Finally, we present how the device performance is affected by varying the film thickness, annealing temperature, device size and stack-layer structure. In addition, the uniformity and the reliability of the selection device such as endurance cycling and retention time were investigated. In particular, the mechanism on operating behavior of the selection device will be presented by analyzing the composition and crystallinity of Cu-doped chalcogenide film by using Auger, energy-dispersive X-ray spectroscopy (EDS), cross sectional transmission electron microscopy (TEM) and X-ray diffraction (XRD). *This work was financially supported by the Ministry of Trade, Industry & Energy(MOTIE, Korea) under Industrial Technology Innovation Program (10068055), the Brain Korea 21 Plus 2016, Republic of Korea and Hanyang University-Samsung Electronics selector research project. Reference [1] Choi, B. J et al., Advanced Materials 23, 3847-3852 (2011). [2] S. Kim et al., VLSI, T240 (2013) [3] S. Jo et al., IEDM, 6.7.1 (2014) [4] G. Burr et al., VLSI, p41 (2012) Figure 1

Resistive random access memory (ReRAM) is one of the candidates to alternate NAND flash memory due to its potential scalability, fast switching speed and low operating power [1]. However, for ReRAM in general, high-voltage forming process is needed to initiate the switching, which normally lead to high power consumption and operational complexity [2]. Therefore, the forming-free operation of ReRAM has been researched globally. In this work, to overcome this high voltage forming operation, the effect of Cu-doping on switching layer of amorphous carbon-oxide ReRAM was studied. ReRAM was fabricated with the structure of tungsten (W) / Cu-doped amorphous carbon oxide / hafnium oxide (HfO2) / platinum (Pt). The buffer layer, hafnium oxide, was inserted to decrease the current level increased excessively due to Cu-doping. It was confirmed that Cu-doping decreased forming voltage and increased memory margin. As comparing the characteristics of the ReRAM with and without Cu-doping at 34-nm pattern size, the forming voltage of Cu-doped ReRAM decreased from 2.7 to 1.95 V and also set voltage of that decreased a little from 1.8 to 1.65 V. From I-V characteristic graph, Cu-doped ReRAM demonstrated that the forming voltage was similar to the set voltage, indicating for the possibility of forming free operation. In addition, the memory margin of that was enlarged from 1.62×102 to 2.64×103. Besides, both of the devices had 106AC endurance cycles, which were excellent performance compared with other ReRAM devices. In our presentation, we report the effect of Cu-doping on electrical characteristics and the switching mechanism by using various analysis tools such as transmission electron microscopy (TEM). * This material is based upon work supported by the Ministry of Trade, Industry & Energy (MOTIE, Korea) under Industrial Technology Innovation Program (10068055). [1] Li Ji; Integrated one diode-one resister architecture in nanopillar SiOxresistive switching memory by nanosphere lithography. Nano Lett. 2014, 14, 813-818 [2] Ruomeng Huang; Forming-free resistive switching of tunable ZnO films grown by atomic layer deposition. Microelectron. Eng. 2016, 161, 7-12 Figure 1

We investigated the sweating response during passive heating (partial submersion up to the umbilical line in 42±0.5℃ water, 30 min) after summer and winter seasonal acclimatization (SA). Testing was performed in July during the summer, 2011 [summer-SA; temp, 25.6±1.8℃; relative humidity (RH), 82.1±8.2%] and in January during the winter, 2012 (winter-SA; temp, -2.7±2.9℃; RH, 65.0±13.1%) in Cheonan (126°52'N, 33.38'E), Republic of Korea. All experiments were carried out in an automated climatic chamber (temp, 25.0±0.5℃: RH, 60.0±3.0%). Fifteen healthy men (age, 23.4±2.5 years; height, 175.0±5.9 cm; weight, 65.3±6.1 kg) participated in the study. Local sweat onset time was delayed during winter-SA compared to that after summer-SA (p< 0.001). Local sweat volume, whole body sweat volume, and evaporative loss volume decreased significantly after winter-SA compared to those after summer-SA (p

The aim of this study was to investigate the expression of cardiac strain and damage in 18 male marathoners with average age of 52.8 ± 5.0 years running at a 308 km ultra-marathon. Blood samples were collected at pre-race, 100 km, 200 km and 308 km check points for the analysis of cardiac muscle injury markers, creatine kinase (CK), creatine kinase-myocardial band (CK-MB), cardiac troponin I (cTnI) and cardiac muscle strain marker, N-terminal pro-brain natriuretic peptide (NT-proBNP). The CK levels increased 1127.2 ± 507.9 IU/L, 5133.8 ± 2492.7 IU/L and 4958.4 ± 2087.9 IU/L at 100 km, 200 km and 308 km, respectively, compared to the pre-race levels. The CK-MB levels increased 20.2 ± 11.2 ng/mL, 73.3 ± 35.6 ng/mL and 68.6 ± 42.6 ng/mL at 100, 200 and 308 km, respectively, compared to the pre-race levels. The CK-MB/CK ratio showed that the CK-MB mass index was within the normal range (2.5%) at 100 km, 200 km and 308 km. The cTnI levels showed no significant difference in all check points. The NT-proBNP levels increased 146.55 ± 92.7 pg/mL, 167.95 ± 111.9 pg/mL and 241.23 ± 121.2 pg/mL at 100, 200 and 308 km, respectively, compared to the pre-race levels. The normal CK-MB mass index (5.0 ng/mL) and the absence of an increase in the cTnI levels during the 308 km ultra-marathon suggested that no myocardial injury despite an elevation in CK-MB. The increase in NT-proBNP levels probably resulted from continuous hemodynamic cardiac stress and represents a transient physiological myocardial protective response.

This paper presents the low power architecture of CalmRISC, a low power 8-bit microcontroller consuming only 0.1 mW per MIPS at 3.0 V, and its efficient coprocessor interface. The architectural consideration of CalmRISC for low power consumption is presented. Some low power circuit design schemes as well as an efficient coprocessor interface scheme in CalmRISC are proposed and discussed. Finally, the implementation results of CalmRISC and MAC816, one of its DSP coprocessors, as well as C-compiler issues are presented.

Oligonol, a phenolic production from lychee, has been reported to exhibit anti-oxidative and anti-inflammatory effects. This study investigated the effect of Oligonol supplementation on circulating levels of prostaglandin E2 (PGE2) and cyclooxygenase (COX)-2, as well as body temperature, after heat stress in 17 healthy human male volunteers (age, 21.6±2.1 years). All experiments were performed in an automated climate chamber (26.0°C±0.5°C, relative humidity 60%±3.0%, air velocity less than 1 m/sec) between 2 and 5 p.m. Subjects ingested an Oligonol (100 mg)-containing beverage or placebo beverage before half-body immersion into hot water (42°C±0.5°C for 30 min). Tympanic and skin temperatures were measured and mean body temperatures were calculated. Serum concentrations of PGE2 and COX-2 were analyzed before, immediately after, and 60 min after immersion. Oligonol intake significantly prevented elevation of tympanic (temperature difference: 0.17°C at Post, P

Scaffolds were fabricated by electrospinning using polycaprolactone (PCL) blended with poly(methyl methacrylate) (PMMA) in ratios of 10/0, 7/3, 5/5 and 3/7. The PCL/PMMA ratio affected the fiber diameter, contact angle, tensile strength and biological in vitro and in vivo properties of the scaffolds, and the 7/3 ratio resulted in a higher mechanical strength than 5/5 and 3/7. In vitro cytotoxicity and proliferation of MG-63 osteoblast cells on these blended scaffolds were examined by MTT assay, and it was found that PCL/PMMA blends are suitable for osteoblast cell proliferation. Confocal images and expression of proliferating cell nuclear antigen confirmed the good proliferation and expression of cells on the 7/3 PCL/PMMA fibrous scaffolds. In vivo bone formation was examined using rat models, and bone formation was observed on the 7/3 PCL/PMMA scaffold within 2 months. In vitro and in vivo results suggest that 7/3 PCL/PMMA scaffolds can be used for bone tissue regeneration.

Fibroblast growth factor 21 (FGF21) plays an important role in the regulation of energy homeostasis during starvation and has an excellent therapeutic potential for the treatment of type 2 diabetes in rodents and monkeys. Acute exercise affects glucose and lipid metabolism by increasing glucose uptake and lipolysis. However, it is not known whether acute exercise affects FGF21 expression. Here, we showed that serum FGF21 level is increased in mice after a single bout of acute exercise, and that this is accompanied by increased serum levels of free fatty acid, glycerol and ketone body. FGF21 gene expression was induced in the liver but not in skeletal muscle and white adipose tissue of mice after acute exercise, and further, the gene expression levels of hepatic peroxisome proliferator-activated receptor alpha (PPAR alpha) and activating transcription factor 4 (ATF4) were also increased. In addition, we observed increased FGF21 level in serum of healthy male volunteers performing a treadmill run at 50 or 80% VO(2)max. These results suggest that FGF21 may also be associated with exercise-induced lipolysis in addition to increased catecholamines and reduced insulin.

We developed a continuously porous scaffold with laminated matrix and bone-like microstructure by a multi-pass extrusion process. In this scaffold, tetragonal ZrO₂, biphasic calcium phosphate and poly-caprolactone layers were arranged in a co-axially laminated unit cell with a channel in the center. The entire matrix phase had a laminated microstructure of alternate lamina of tetragonal ZrO₂, biphasic calcium phosphate and poly-caprolactone--biphasic calcium phosphate with optimized designed thickness and channeled porosity. Each of the continuous pores was coaxially encircled by the poly-caprolactone--biphasic calcium phosphate layer, biphasic calcium phosphate layer and finally tetragonal ZrO₂ layer, one after the other. Before extrusion, 5 vol% graphite powder was mixed with tetragonal ZrO₂ to ensure pores in the outer layer and connectivity among the lamellas. The design strategy is aimed to incorporate a lamellar microstructure like the natural bone in the macro-scaled ceramic body to investigate the strengthening phenomenon and pave the way for fabricating complex microstructure of natural bone could be applied for whole bone replacement. The final fabricated scaffold had a compressive strength of 12.7 MPa and porosity of 78 vol% with excellent cell viability, cell attachment and osteocalcin and collagen expression from cultured MG63 cells on scaffold.

The aim of the present study was to quantitatively investigate the age and sex-related differences in sudomotor function in healthy humans. The quantitative sudomotor axon reflex test (QSART) with iontophoresis (2 mA for 5 min) and 10% acetylcholine (ACh) was performed to determine axon reflex-mediated (AXR), with and without iotophoresis (AXR(1) and AXR(2), respectively), and directly activated (DIR) sweating. All experiments were conducted under thermoneutral conditions (temperature 24.0 ± 0.5°C; relative humidity 40 ± 3%). In general, men had enhanced values of onset time of AXR, sweat rates, activated sweat gland density (SGD) and activated sweat gland output (SGO) than women, but not in all cases. The onset time of AXR (r(2) = 0.567; P

We examined serum levels of prostaglandin E2 (PGE2), cyclooxygenase (COX)-2 and orexin before and after heat acclimation (HA) to test the hypothesis that decreased basal body temperature due to HA correlate with circulating levels of these key thermoregulatory molecules. Nine healthy human male volunteers were recruited (age, 21.9±2.7 years). The subjects were exposed to half-body immersion in hot water (42±0.5°C) at the same time of day (2-5p.m.) on alternate days for 3 weeks. The HA protocol included 10 bouts of 30min immersion. All experiments were performed in an automated climate chamber (temperature, 26.0±0.5°C; relative humidity, 60±3.0%; air velocity

A novel nanofiber membrane was fabricated by electrospinning composed of polyvinyl phosphonic acid (PVPA) and polyvinyl alcohol (PVA). Stabilization was done due to the high dissolvability of the membrane when in contact with water. Physical treatment was done by exposure to heat at 150°C in a vacuum environment at different periods of time. Chemical crosslinking was done by immersion in methanol and methanol/ glutaraldehyde. A heat-exposed membrane was also further crosslinked chemically. All conditions were compared with regards to its effect on the material properties of the membranes and its biological responsein vitrowith MG-63 osteoblast-like cell line. Visual examination and dimensional analyses showed that heat treatment produced discoloration on the membrane surface and chemical crosslinking reduced membrane dimensions. Tensile strength and strain improved in crosslinked membranes compared to noncrosslinked counterpart. Swelling and degradation was also investigated and was seen to vary depending on the crosslinking condition. Biocompatibility was observed to be more favorable in heat-treated membranes.

In this study, a novel bilayer scaffold composed of electrospun polycaprolactone and poly(lacto-co-glycolic acid) (PCL/PLGA) membrane and glutaraldehyde (3.5% v/v) cross-linked chitosan/gelatin hydrogel was fabricated using two methods: electrospinning of the membrane onto the lyophilized hydrogel (BS-1) and membrane underlaying and casting method (BS-2). The morphology of the fabricated scaffolds was examined by scanning electron microscope (SEM). Mechanical strength, porosity, swelling capacity, and biodegradation rates of the scaffolds were also characterized. The in vitro biocompatibility of the materials was investigated by assessing cytotoxicity and cell proliferation on the material was measured using MTT assay. In addition, cell adhesion on the material was investigated by SEM. The BS-2 was grafted in Sprague-Dawley rats to determine its in vivo behavior and biocompatibility. The experimental results showed that the addition of the membrane layer to the hydrogel decreased swelling and degradation rates and provided ease of handling during implantation. Grafted BS-2 showed normal wound healing and no major inflammatory reaction was observed.

An optimization problem, formulated using a nonlinear least-squares approach, was used to estimate parameters for kinetic models of the three isoforms of the kidney-specific Na-K-2Cl (NKCC2) cotransporter. Specifically, the optimization problem estimates the magnitude of model parameters (i.e., off-binding and translocation rate constants) by minimizing the distance between model unidirectional fluxes and published unidirectional 86Rb+ uptake curves for the A, B, and F isoforms of the NKCC2 cotransporter obtained in transfected Xenopus oocytes. By using different symmetry assumptions, NKCC2 models with five, six, seven, or eight parameters were evaluated. The optimization method identified parameter sets that yielded computed unidirectional fluxes consistent with the uptake data. However, the parameter values were not unique, in that systematic exploration of the parameter space revealed alternative parameter sets that fit the data with similar accuracy. Finally, we demonstrate that the optimization method can identify parameter sets for the three transporter isoforms that differ only in ion binding affinities, a result that is consistent with a published mutagenesis analysis of the molecular and structural bases for the differences in 86Rb+ uptake among the A, B, and F isoforms. These NKCC2 cotransporter models will facilitate the development of larger scale models of ion transport by thick ascending limb cells.