A Multi-Functional Physiological Hybrid-Sensing E-Skin Integrated Interface for Wearable IoT Applications.

This paper presents a flexible multi-functional physiological sensing system that provides multiple noise-immune readout architectures and hybrid-sensing capability with an analog pre-processing scheme. The proposed multi-functional system is designed to support five physiological detection methodologies of piezo-resistive, pyro-resistive, electro-metric, opto-metric and their hybrid, utilizing an in-house multi-functional e-skin device, in-house flexible electrodes and a LED-photodiode pair. For their functional verification, eight representative physiological detection capabilities were demonstrated using wearable device prototypes. Especially, the hybrid detection method includes an innovative continuous measurement of blood pressure (BP) while most previous wearable devices are not ready for it. Moreover, for effective implementation in the form of the wearable device, post-processing burden of the hybrid method was much reduced by integrating a proposed analog pre-processing scheme, where only simple counting process and calibration remain to estimate the BP. This multi-functional sensor readout circuits and their hybrid-sensing interface are fully integrated into a single readout integrated circuit (ROIC), which is designed to implement three readout paths: two electrometric readout paths and one impedometric readout path. For noise-immune detection of the e-skin sensor, a pseudo-differential front-end with a ripple reduction loop is proposed in the impedometric readout path, and also state-of-the-art body-oriented noise reduction techniques are adopted for the electrometric readout path. The ROIC is fabricated in a CMOS process and in-house e-skin devices and flexible electrodes are also fabricated.

A Portable Phase-Domain Magnetic Induction Tomography Transceiver with Phase-Band Auto-Tracking and Frequency-Sweep Capabilities.

This paper presents a portable magnetic induction tomography (MIT) transceiver integrated circuit to miniaturize conventional equipment-based MIT systems. The miniaturized MIT function is enabled through single-chip transceiver implementation. The proposed MIT transceiver utilizes a phase-locked loop (PLL) for frequency sweeping and a phase-domain sigma⁻delta modulator with phase-band auto-tracking for a full-range fine-phase resolution. The designed transceiver is fabricated and verified to achieve the measured signal to noise and distortion ratio (SNDR) of 101.7 dB. Its system-level prototype including in-house magnetic sensor coils is manufactured and functionally verified for four different material types.

A Three-Step Resolution-Reconfigurable Hazardous Multi-Gas Sensor Interface for Wireless Air-Quality Monitoring Applications.

This paper presents a resolution-reconfigurable wide-range resistive sensor readout interface for wireless multi-gas monitoring applications that displays results on a smartphone. Three types of sensing resolutions were selected to minimize processing power consumption, and a dual-mode front-end structure was proposed to support the detection of a variety of hazardous gases with wide range of characteristic resistance. The readout integrated circuit (ROIC) was fabricated in a 0.18 µm CMOS process to provide three reconfigurable data conversions that correspond to a low-power resistance-to-digital converter (RDC), a 12-bit successive approximation register (SAR) analog-to-digital converter (ADC), and a 16-bit delta-sigma modulator. For functional feasibility, a wireless sensor system prototype that included in-house microelectromechanical (MEMS) sensing devices and commercial device products was manufactured and experimentally verified to detect a variety of hazardous gases.

A Wireless ExG Interface for Patch-Type ECG Holter and EMG-Controlled Robot Hand.

This paper presents a wearable electrophysiological interface with enhanced immunity to motion artifacts. Anti-artifact schemes, including a patch-type modular structure and real-time automatic level adjustment, are proposed and verified in two wireless system prototypes of a patch-type electrocardiogram (ECG) module and an electromyogram (EMG)-based robot-hand controller. Their common ExG readout integrated circuit (ROIC), which is reconfigurable for multiple physiological interfaces, is designed and fabricated in a 0.18 µm CMOS process. Moreover, analog pre-processing structures based on envelope detection are integrated with one another to mitigate signal processing burdens in the digital domain effectively.

Calcium signaling in pancreatic ß-cells in health and in Type 2 diabetes.

Changes in cytosolic free Ca(2+) concentration ([Ca(2+)]c) play a crucial role in the control of insulin secretion from the electrically excitable pancreatic ß-cell. Secretion is controlled by the finely tuned balance between Ca(2+) influx (mainly through voltage-dependent Ca(2+) channels, but also through voltage-independent Ca(2+) channels like store-operated channels) and efflux pathways. Changes in [Ca(2+)]c directly affect [Ca(2+)] in various organelles including the endoplasmic reticulum (ER), mitochondria, the Golgi apparatus, secretory granules and lysosomes, as imaged using recombinant targeted probes. Because most of these organelles have specific Ca(2+) influx and efflux pathways, they mutually influence free [Ca(2+)] in the others. In this article, we review the mechanisms of control of [Ca(2+)] in various compartments and particularly the cytosol, the endoplasmic reticulum ([Ca(2+)]ER), acidic stores and mitochondrial matrix ([Ca(2+)]mito), focusing chiefly on the most important physiological stimulus of ß-cells, glucose. We also briefly review some alterations of ß-cell Ca(2+) homeostasis in Type 2 diabetes.

Tolbutamide controls glucagon release from mouse islets differently than glucose: involvement of K(ATP) channels from both α-cells and δ-cells.

We evaluated the role of ATP-sensitive K⁺ (K(ATP)) channels, somatostatin, and Zn²âº in the control of glucagon secretion from mouse islets. Switching from 1 to 7 mmol/L glucose inhibited glucagon release. Diazoxide did not reverse the glucagonostatic effect of glucose. Tolbutamide decreased glucagon secretion at 1 mmol/L glucose (G1) but stimulated it at 7 mmol/L glucose (G7). The reduced glucagon secretion produced by high concentrations of tolbutamide or diazoxide, or disruption of K(ATP) channels (Sur1(-/-) mice) at G1 could be inhibited further by G7. Removal of the somatostatin paracrine influence (Sst(-/-) mice or pretreatement with pertussis toxin) strongly increased glucagon release, did not prevent the glucagonostatic effect of G7, and unmasked a marked glucagonotropic effect of tolbutamide. Glucose inhibited glucagon release in the absence of functional K(ATP) channels and somatostatin signaling. Knockout of the Zn²âº transporter ZnT8 (ZnT8(-/-) mice) did not prevent the glucagonostatic effect of glucose. In conclusion, glucose can inhibit glucagon release independently of Zn²âº, K(ATP) channels, and somatostatin. Closure of K(ATP) channels controls glucagon secretion by two mechanisms, a direct stimulation of α-cells and an indirect inhibition via somatostatin released from δ-cells. The net effect on glucagon release results from a balance between both effects.

Molecular detection of Anaplasma, Bartonella, and Borrelia species in ticks collected from migratory birds from Hong-do Island, Republic of Korea.

Bird migration is a recurring annual and seasonal event undertaken by more than 100 species of birds in the southeast Asian and northeast Palearctic regions that pass through or remain for short periods from April to May and September to November at Hong-do Island, Republic of Korea (ROK). A total of 212 ticks (40 Haemaphysalis flava, 12 H. longicornis, 146 Ixodes turdus, 13 I. nipponensis, and 1 I. ornithophila) were collected from 65/2,161 (3.0%) migratory birds consisting of 21 species that were captured from January, 2008, through December, 2009, as part of the Migratory Birds Center, Hong-do bird banding program for studying bird migration patterns. Adult ticks were assayed individually while larvae and nymphs were pooled (1-22 and 1-6 ticks per pool, respectively) into 31 and 65 pools, respectively. Ticks were assayed for zoonotic pathogens by PCR using 16S rRNA, heat shock protein (groEL), and internal transcribed spacer (ITS) gene primers to amplify genera specific for Anapalsma, Bartonella, and Borrelia PCR amplicons. Using the 16S rRNA-based nested PCR, A. phagocytophilum (n=1) was detected in I. nipponensis collected from Zoothera sibirica and A. bovis (n=1) was detected in I. turdus collected from Emberiza chrysophrys. Borrelia turdi 16S rRNA genes (n=3) were detected in I. turdus and I. nipponensis collected from Turdus pallidus and Zoothera aurea. Borrelia spp. 16S rRNA genes (n=4) were detected in Ixodes ticks collected from Emberiza tristrami, T. pallidus, and Z. aurea. The Bartonella grahamii ITS gene (n=1) was detected by nested PCR assay in I. turdus collected from Z. aurea. These results provide insight into the potential role of migratory birds in the dispersal of ticks and associated tick-borne pathogens throughout their ranges in Asia.

Improved transplantation outcome through delivery of DNA encoding secretion signal peptide-linked glucagon-like peptide-1 into mouse islets.

Glucagon-like peptide-1 (GLP-1) stimulates cell proliferation and has anti-apoptotic effects on pancreatic islet ß cells. In our previous study, the transduction of mouse islets with a recombinant adenovirus containing GLP-1 cDNA enhanced islet graft survival. In this study, we sought to deliver the GLP-1 gene using a nonviral vector, which raises fewer safety issues in clinical application. We constructed a plasmid, pß-SP-GLP-1, in which a secretion signal peptide (SP) was inserted to increase GLP-1 secretion, and transfected mouse islets using the nonviral carrier Effectene. Transfection of pß-SP-GLP-1 induced a significant increase in bioactive GLP-1 levels in islet cultures. Islets transfected with pß-SP-GLP-1 were protected from H2 O2 -induced cell damage in vitro. In addition, glucose-stimulated insulin secretion was significantly increased in pß-SP-GLP-1-transfected islets. Diabetic syngeneic mice transplanted under the kidney capsule with a marginal mass of pß-SP-GLP-1-transfected islets rapidly became normoglycemic, with 88% of recipients being normoglycemic at 30 days post-transplantation compared with 52% of mice that received pß-transfected islet grafts (P < 0.05). Islet grafts retrieved 7 days after transplantation revealed that the pß-SP-GLP-1-transfected group had significantly more Ki67-positive cells as compared with the pß-transfected group. In conclusion, delivery of a plasmid containing a secretion SP and GLP-1 cDNA using a nonviral carrier leads to efficient secretion of GLP-1 in mouse islet cells, enhances islet cell survival during the early post-transplant period, and improves islet transplantation outcome.

Louse flies (Diptera: Hippoboscidae: Ornithomyinae) of the Republic of Korea: an updated checklist, including two new records of bird louse flies.

One genus, Ornithoica Rondani, and two species, Ornithoica momiyamai Kishida, and O. unicolor Speiser, are reported for the first time from the Republic of Korea. A total of six species, including two new records, of louse flies were collected from 78 birds belonging to 35 species from Seoul and Incheon Metropolitan Areas and Gyeonggi, Gangwon, Gyeongsangbuk, Jeollabuk, and Jeollanam Provinces, 2005-2010. An updated checklist of Korean hippoboscids consisting of seven genera (Hippobosca L., Icosta Speiser, Lipoptena Nitzsch, Ornithoica Rondani, Ornithoctona Speiser, Ornithomya Lattreille, and Ornithophila Rondani) and 11 species is presented, including hosts, collection records, and repositories.

Effect of glucagon-like peptide-1 gene expression on graft function in mouse islet transplantation.

This study investigated the effect of local glucagon-like peptide-1 (GLP-1) production within mouse islets on cytoprotection in vitro and in vivo by gene transfer of GLP-1. Transduction of recombinant adenovirus vector expressing GLP-1 (rAd-GLP-1) induced a significant increase in bioactive GLP-1 in the mouse islet culture, whereas transduction with adenovirus vector expressing ß-galactosidase (rAd-LacZ), as a control, had no effect on GLP-1 secretion. Islets transduced with rAd-GLP-1 were protected from H(2) O(2) -induced cell damage in vitro. In addition, glucose-stimulated insulin secretion was significantly increased in rAd-GLP-1-transduced islets. When transplanted under the kidney capsule of diabetic syngeneic mice, islet grafts retrieved 4 or 7 days after transplantation revealed that the rAd-GLP-1-transduced group had significantly more Ki67-positive cells as compared with the rAd-LacZ-transduced group. Regarding blood glucose control, diabetic mice transplanted with a marginal mass of rAd-GLP-1-transduced islets became normoglycemic more rapidly and 78% of the recipients were normoglycemic at 35 days post-transplant, whereas only 48% of the mice transplanted with rAd-LacZ-transduced islets were normoglycemic (P < 0.05). In conclusion, delivery of the GLP-1 gene to islets enhanced islet cell survival during the early post-transplant period, and preserved islet mass and functions over time in the transplants.

Ticks collected from selected mammalian hosts surveyed in the Republic of Korea during 2008-2009.

A tick survey was conducted to determine the relative abundance and distribution of ticks associated with selected mammals in the Republic of Korea (ROK) during 2008-2009. A total of 918 ticks were collected from 76 mammals (6 families, 9 species) captured at 6 provinces and 3 Metropolitan Cities in ROK. Haemaphysalis longicornis (54.4%) was the most frequently collected tick, followed by Haemaphysalis flava (28.5%), Ixodes nipponensis (7.6%), Ixodes pomerantzevi (4.8%), Ixodes persulcatus (4.6%), and Haemaphysalis japonica (0.1%). Adults (57.0%) and nymphs (28.7%) of Ixodes and Haemaphysalis spp. were collected most frequently from medium or large mammals in this survey, while few larvae (14.3%) were collected. Hydropotes inermis was the most frequently captured mammal (52.6%), with a 16.4 tick index and 5 of 6 species of ticks collected during this survey. H. longicornis (69.7%) was the predominant tick collected from H. inermis, followed by H. flava (22.2%), I. persulcatus (6.1%), I. nipponensis (1.8%), and H. japonica (0.2%).

Effect of hypoxia-inducible VEGF gene expression on revascularization and graft function in mouse islet transplantation.

For gene transfer strategies to improve islet engraftment, vascular endothelial growth factor (VEGF) expression should be regulated in a way that matches the transient nature of revascularization with simultaneously avoiding undesirable effects of overexpression. The aim of this study was to investigate the effects of hypoxia-inducible VEGF gene transfer using the RTP801 promoter on islet grafts. We implanted pSV-hVEGF transfected, pRTP801-hVEGF transfected or nontransfected mouse islets under the kidney capsule of streptozotocin-induced diabetic syngeneic mice. Human VEGF immunostaining of day 3 grafts revealed that the pRTP801-hVEGF transfected group had higher hVEGF expression compared with the pSV-hVEGF transfected group. BS-1 staining of day 3 grafts from the pRTP801-hVEGF transfected group showed the highest vascular density, which was comparable with day 6 grafts from the nontransfected group. In 360 islet equivalent (IEQ)-transplantation which reverted hyperglycemia in all mice, the area under the curve of glucose levels during intraperitoneal glucose tolerance test 7 weeks post-transplant was lower in mice transplanted with pRTP801-hVEGF transfected grafts compared with mice transplanted with nontransfected grafts. In 220 IEQ-transplantations, diabetic mice transplanted with pRTP801-hVEGF islets became normoglycemic more rapidly compared with mice transplanted with pSV-hVEGF or nontransfected islets, and diabetes reversal rate after 50 days was 90%, 68%, and 50%, respectively. In conclusion, our results indicate that regulated overexpression of hVEGF in a hypoxia-inducible manner enhances islet vascular engraftment and preserves islet function overtime in transplants.

RAGE ligands induce apoptotic cell death of pancreatic ß-cells via oxidative stress.

Activation of the receptor for advanced glycation endproducts (RAGE) by its ligands leads to cellular damage contributing to diabetic complications. It is not clearly known whether RAGE ligands influence pancreatic ß-cells. In this study, we investigated the expression of RAGE in islet cells and the effect of RAGE ligands, S100b and HMG-1, on islet cells. RAGE was expressed in INS-1 cells and isolated rat and human islets at mRNA and protein levels. RAGE and its ligand, S100b, were detected on islet cells in 28-week-old diabetic OLETF rats. Both S100b and HMG-1 induced apoptotic cell death of INS-1 and islet cells. This INS-1 cell apoptosis was accompanied by increased intracellular oxidative stress and inhibited by antioxidants or a NADPH oxidase inhibitor. Our results showing S100b/RAGE expression on islets of diabetic rat model and RAGE ligands-induced islet cell apoptosis via NADPH oxidase-mediated ROS generation suggest that RAGE ligands-RAGE interaction may contribute not only to the development of diabetic complications but also to the progressive ß-cell loss in type 2 diabetes by inducing oxidative stress.

A comparison of non-viral vectors for gene delivery to pancreatic beta-cells: delivering a hypoxia-inducible vascular endothelial growth factor gene to rat islets.

Although non-viral vectors are relatively safe, they have very low gene transfection efficiency, especially in pancreatic islet cells. To provide information on the use of non-viral vectors for transfecting genes into pancreatic islet cells, a comparative evaluation of non-viral options was performed. In vitro experiments were used to compare the transfection efficiency of three classes of non-viral vectors: Effectene, polyethylenimine (PEI, 25 kDa) and hemagglutinating virus of Japan-envelope (HVJ-E), into insulinoma cells (INS-1) and rat islets. Vascular endothelial growth factor (VEGF) gene with hypoxia-inducible RTP801 promoter was delivered into rat islets with Effectene and VEGF secretion under hypoxia was measured in the culture media. Luciferase activity and GFP assays indicated that Effectene exhibited the highest transfection efficiency, and HVJ-E was not suitable for transfection into pancreatic beta-cells. The cytotoxicity of Effectene was found to be similar to that of 25-kDa PEI by 7-amino actinomycin D (7-AAD) flow cytometry and acridine orange/propidium iodide (AO/PI) assays. When RTP801 promoter-VEGF plasmid was delivered to rat islets with Effectene, VEGF secretion increased specifically in islets under hypoxia. In conclusion, Effectene showed higher gene-delivery efficiency for pancreatic islets compared with other classes of non-viral delivery systems and is promising as a gene delivery agent for pretransplant ex vivo gene therapy of islets.

Dose-related cytoprotective effect of alpha-lipoic acid on hydrogen peroxide-induced oxidative stress to pancreatic beta cells.

alpha-Lipoic acid (alpha-LA), an antioxidant used for diabetic polyneuropathy, was reported to induce AMP-activated protein kinase activation and reductions in insulin secretion in pancreatic beta-cells at high concentrations (> or = 500 micromol/l). This study investigated whether alpha-LA has a protective role under oxidative stress in beta-cells and its effect is dose-related. In INS-1 cells treated with alpha-LA (150-1200 micromol/l) for 24 h, alpha-LA itself (> or = 300 micromol/l) induced apoptotic death dose-dependently. However, pre-treatment with 150 and 300 micromol/l alpha-LA reduced the hydrogen peroxide-induced apoptosis in INS-1 cells and isolated islets. alpha-LA alleviated hydrogen peroxide-induced reactive oxygen species production, mitochondrial membrane depolarization and c-JNK activation in beta-cells. alpha-LA induced phosphoinositide 3-kinase-dependent Akt phosphorylation in INS-1 cells. While alpha-LA is harmful to beta-cells at high concentrations in vitro, it has potential cytoprotective effects on beta-cells under oxidative stress as in diabetes by its antioxidant properties and possibly by Akt phosphorylation at clinically relevant concentrations.

The favorable outcome of human islet transplantation in Korea: experiences of 10 autologous transplantations.

BACKGROUND: Cystic neoplasms of the pancreas are an increasingly diagnosed entity, and surgical resection of the pancreas is advocated. Islet autotransplantation is a therapeutic approach used to prevent diabetes in cases of pathologically benign neoplasm after major pancreatectomy. METHODS: A total of 10 patients underwent pancreatectomy with islet autotransplantation. To evaluate islet transplantation efficiency, the authors compared 23 subjects who did not undergo islet transplantation after partial pancreatectomy with 87 subjects with normal glucose tolerance and with 77 diabetic subjects that did not undergo pancreatectomy. RESULTS: Ten female patients with nine cystic neoplasms and one patient with pancreatic injury underwent transplantation. Their mean islet equivalents (IEQ) was 3,159 IEQ/kg. During follow-up, two recipients required insulin or oral agents. At the 12-month follow-up, homeostasis model assessment (HOMA)-beta was 77.36+/-17.68, the insulinogenic index (INSindex) was 0.49+/-0.11, and fasting C-peptide and hemoglobin A1c were 1.28+/-0.18 ng/mL and 5.73+/-0.26%, respectively. Islet replacement was found to increase HOMA-beta by approximately 17% compared with distal pancreatectomy in normal glucose tolerance subjects without islet autotransplantation and by 46% compared with distal pancreatectomy diabetes subjects without islet autotransplantation. Factors different in the two insulin and oral hypoglycemic agent (OHA)-requiring recipients and the eight insulin- and OHA-free recipients were pancreatectomy extent, preoperative glucose metabolism insufficiency, age, and underlying cystic neoplasm disease. CONCLUSIONS: Even partial islet graft function can have a beneficial metabolic effect on the recipient in terms of metabolic parameters such as HOMA-beta and INSindex. This study suggests that islet replacement should be considered for experimental procedures in benign pancreatic conditions.

Effective glycemic control achieved by transplanting non-viral cationic liposome-mediated VEGF-transfected islets in streptozotocin-induced diabetic mice.

Hypoxic damage is one of the major causes of islet graft failure and VEGF is known to play a crucial role in revascularization. To address the effectiveness of a cationic lipid reagent as a VEGF gene carrier, and the beneficial effect of VEGF-transfected islets on glycemic control, we used effectene lipid reagent in a transfection experiment using mouse islets. Transfection efficiencies were highest for 4 microg/microgL cDNA and 25 microgL effectene and cell viabilities were also satisfactory under this condition, and the overproduction of VEGF mRNA and protein were confirmed from conditioned cells. A minimal number of VEGF-transfected islets (100 IEQ/animal) were transplanted into streptozotocin (STZ)-induced diabetic mice. Hyperglycemia was not controlled in the islet transplantation (IT)-alone group (0/8) (non- diabetic glucose mice number/total recipient mice number) or in the IT-pJDK control vector group (0/8). However, hyperglycemia was completely abrogated in the IT-pJDK-VEGF transduced group (8/8), and viable islets and increased VEGF-transfected grafts vascularization were observed in renal capsules.