Colorectal Cancer Stem Cell Subtypes Orchestrate Distinct Tumor Microenvironments.

Several classification systems have been developed to define tumor subtypes in colorectal cancer (CRC). One system proposes that tumor heterogeneity derives in part from distinct cancer stem cell populations that co-exist as admixtures of varying proportions. However, the lack of single cell resolution has prohibited a definitive identification of these types of stem cells and therefore any understanding of how each influence tumor phenotypes. Here were report the isolation and characterization of two cancer stem cell subtypes from the SW480 CRC cell line. We find these cancer stem cells are oncogenic versions of the normal Crypt Base Columnar (CBC) and Regenerative Stem Cell (RSC) populations from intestinal crypts and that their gene signatures are consistent with the "Admixture" and other CRC classification systems. Using publicly available single cell RNA sequencing (scRNAseq) data from CRC patients, we determine that RSC and CBC cancer stem cells are commonly co-present in human CRC. To characterize influences on the tumor microenvironment, we develop subtype-specific xenograft models and we define their tumor microenvironments at high resolution via scRNAseq. RSCs create differentiated, inflammatory, slow growing tumors. CBCs create proliferative, undifferentiated, invasive tumors. With this enhanced resolution, we unify current CRC patient classification schema with TME phenotypes and organization.

Estimation of Validity of A-Mode Ultrasound for Measurements of Muscle Thickness and Muscle Quality.

This study aimed to determine whether amplitude modulation (A-mode) ultrasound (US) provides accurate and reliable measurements comparable to those obtained using brightness modulation (B-mode) US under diverse conditions. Thirty healthy participants (15 women and 15 men) underwent measurements of subcutaneous fat thickness (SFT), muscle thickness (MT), and muscle quality (MQ) in the trapezius and biceps brachii muscles using both US modes before and after exercises designed to stimulate the respective muscles. Among the three key indices, the results demonstrated the high validity of the A-mode, with minimal mean differences (MDs) between the two devices less than 0.91 mm and intra-class correlation coefficients (ICCs) exceeding 0.95 for all measures. In addition, the correlation coefficients between the error scores and average scores for the trapezius and biceps brachii suggested no evidence of systematic error. The trapezius MT and MQ significantly increased, and the biceps brachii MT significantly increased after the exercises (p < 0.05). Notably, both the A- and B-modes exhibited the same trend in these post-exercise changes in the muscle. This study suggests that low-cost and low-resolution A-mode US provides measurements of SFT, MT, and MQ similar to the more expensive, high-resolution B-mode imaging. A-mode US is an affordable and portable alternative for muscle assessment.

Power-Efficient LFP-Adaptive Dynamic Zoom-and-Track Incremental ΔΣ Front-End for Dual-Band Subcortical Recordings.

We report a power-efficient analog front-end integrated circuit (IC) for multi-channel, dual-band subcortical recordings. In order to achieve high-resolution multi-channel recordings with low power consumption, we implemented an incremental ΔΣ ADC (IADC) with a dynamic zoom-and-track scheme. This scheme continuously tracks local field potential (LFP) and adaptively adjusts the input dynamic range (DR) into a zoomed sub-LFP range to resolve tiny action potentials. Thanks to the reduced DR, the oversampling rate of the IADC can be reduced by 64.3% compared to the conventional approach, leading to significant power reduction. In addition, dual-band recording can be easily attained because the scheme continuously tracks LFPs without additional on-chip hardware. A prototype four-channel front-end IC has been fabricated in 180 nm standard CMOS processes. The IADC achieved 11.3-bit ENOB at 6.8 µW, resulting in the best Walden and SNDR FoMs, 107.9 fJ/c-s and 162.1 dB, respectively, among two different comparison groups: the IADCs reported up to date in the state-of-the-art neural recording front-ends; and the recent brain recording ADCs using similar zooming or tracking techniques to this work. The intrinsic dual-band recording feature reduces the post-processing FPGA resources for subcortical signal band separation by >45.8%. The front-end IC with the zoom-and-track IADC showed an NEF of 5.9 with input-referred noise of 8.2 µVrms, sufficient for subcortical recording. The performance of the whole front-end IC was successfully validated through in vivo animal experiments.

In vivo characterization of Drosophila golgins reveals redundancy and plasticity of vesicle capture at the Golgi apparatus.

The Golgi is the central sorting station in the secretory pathway and thus the destination of transport vesicles arriving from the endoplasmic reticulum and endosomes and from within the Golgi itself. Cell viability, therefore, requires that the Golgi accurately receives multiple classes of vesicle. One set of proteins proposed to direct vesicle arrival at the Golgi are the golgins, long coiled-coil proteins localized to specific parts of the Golgi stack. In mammalian cells, three of the golgins, TMF, golgin-84, and GMAP-210, can capture intra-Golgi transport vesicles when placed in an ectopic location. However, the individual golgins are not required for cell viability, and mouse knockout mutants only have defects in specific tissues. To further illuminate this system, we examine the Drosophila orthologs of these three intra-Golgi golgins. We show that ectopic forms can capture intra-Golgi transport vesicles, but strikingly, the cargo present in the vesicles captured by each golgin varies between tissues. Loss-of-function mutants show that the golgins are individually dispensable, although the loss of TMF recapitulates the male fertility defects observed in mice. However, the deletion of multiple golgins results in defects in glycosylation and loss of viability. Examining the vesicles captured by a particular golgin when another golgin is missing reveals that the vesicle content in one tissue changes to resemble that of a different tissue. This reveals a plasticity in Golgi organization between tissues, providing an explanation for why the Golgi is sufficiently robust to tolerate the loss of many of the individual components of its membrane traffic machinery.

A 3.1-5.2GHz, Energy-Efficient Single Antenna, Cancellation-Free, Bitwise Time-Division Duplex Transceiver for High Channel Count Optogenetic Neural Interface.

We report an energy-efficient, cancellation-free, bit-wise time-division duplex (B-TDD) transceiver (TRX) for real-time closed-loop control of high channel count neural interfaces. The proposed B-TDD architecture consists of a duty-cycled ultra-wide band (UWB) transmitter (3.1-5 GHz) and a switching U-NII band (5.2 GHz) receiver. An energy-efficient duplex is realized in a single antenna without power-hungry self-interference cancellation circuits which are prevalently used in the conventional full-duplex, single antenna transceivers. To suppress the interference between up- and down-links and enhance the isolation between the two, we devised a fast-switching scheme in a low noise amplifier and used 5× oversampling with a built-in winner-take-all voting in the receiver. The B-TDD transceiver was fabricated in 65 nm CMOS RF process, achieving low energy consumption of 0.32 nJ/b at 10 Mbps in the receiver and 9.7 pJ/b at 200 Mbps in the transmitter, respectively. For validation, the B-TDD TRX has been integrated with a µLED optoelectrode and a custom analog frontend integrated circuit in a prototype wireless bidirectional neural interface system. Successful in-vivo operation for simultaneously recording broadband neural signals and optical stimulation was demonstrated in a transgenic rodent.

A Miniaturized 256-Channel Neural Recording Interface With Area-Efficient Hybrid Integration of Flexible Probes and CMOS Integrated Circuits.

We report a miniaturized, minimally invasive high-density neural recording interface that occupies only a 1.53 mm2 footprint for hybrid integration of a flexible probe and a 256-channel integrated circuit chip. To achieve such a compact form factor, we developed a custom flip-chip bonding technique using anisotropic conductive film and analog circuit-under-pad in a tiny pitch of 75 µm. To enhance signal-to-noise ratios, we applied a reference-replica topology that can provide the matched input impedance for signal and reference paths in low-noise aimpliers (LNAs). The analog front-end (AFE) consists of LNAs, buffers, programmable gain amplifiers, 10b ADCs, a reference generator, a digital controller, and serial-peripheral interfaces (SPIs). The AFE consumes 51.92 µW from 1.2 V and 1.8 V supplies in an area of 0.0161 mm2 per channel, implemented in a 180 nm CMOS process. The AFE shows > 60 dB mid-band CMRR, 6.32 µVrms input-referred noise from 0.5 Hz to 10 kHz, and 48 MΩ input impedance at 1 kHz. The fabricated AFE chip was directly flip-chip bonded with a 256-channel flexible polyimide neural probe and assembled in a tiny head-stage PCB. Full functionalities of the fabricated 256-channel interface were validated in both in vitro and in vivo experiments, demonstrating the presented hybrid neural recording interface is suitable for various neuroscience studies in the quest of large scale, miniaturized recording systems.

Current Review of Optical Neural Interfaces for Clinical Applications.

Neural interfaces, which enable the recording and stimulation of living neurons, have emerged as valuable tools in understanding the brain in health and disease, as well as serving as neural prostheses. While neural interfaces are typically based on electrical transduction, alternative energy modalities have been explored to create safe and effective approaches. Among these approaches, optical methods of linking neurons to the outside world have gained attention because light offers high spatial selectivity and decreased invasiveness. Here, we review the current state-of-art of optical neural interfaces and their clinical applications. Optical neural interfaces can be categorized into optical control and optical readout, each of which can be divided into intrinsic and extrinsic approaches. We discuss the advantages and disadvantages of each of these methods and offer a comparison of relative performance. Future directions, including their clinical opportunities, are discussed with regard to the optical properties of biological tissue.

Berteroin ameliorates lipid accumulation through AMPK-mediated regulation of hepatic lipid metabolism and inhibition of adipocyte differentiation.

AIMS: Berteroin (5-methylthiopentyl isothiocyanate) is a naturally occurring sulforaphane analog containing a non-oxidized sulfur atom in cruciferous vegetables. The objectives of the present study were to determine the effects of berteroin on lipid metabolism in hepatocytes and adipocytes and to elucidate the mechanisms involved. MAIN METHODS: The effect of berteroin on lipid metabolism were evaluated in liver X receptor α agonist-stimulated HepG2 cells and adipocyte differentiation-induced 3T3-L1 cells using MTT assay, western blot, real time polymerase chain reaction, oil red O staining, and triglyceride assay. KEY FINDINGS: T0901317 treatment increased the expression of sterol regulatory element binding protein (SREBP)-1c, a major transcription factor that mediates lipogenesis, and berteroin pretreatment significantly inhibited the expressions of T0901317-induced SREBP-1c and lipogenic genes. Especially, berteroin had a greater inhibitory effect on T0901317-induced SREBP-1c activation than sulforaphane, AICAR, or metformin. Berteroin also markedly suppressed lipid droplet formations and triglyceride accumulations caused by both T0901317 stimulation in HepG2 hepatocytes and differentiation induction in 3T3-L1 preadipocytes. However, berteroin significantly increased the expression of mitochondrial fatty acid oxidation-related genes (carnitine palmitoyltransferase 1 (CPT-1) and peroxisome proliferator-activated receptor gamma coactivator-1α) and the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) in HepG2 cells. Interestingly, effects of berteroin on the expressions of SREBP-1c protein and CPT-1 mRNA were remarkably prevented by compound C (an AMPK inhibitor). SIGNIFICANCE: Our results suggest berteroin-inhibited hepatic lipid accumulation and adipocyte differentiation might be mediated by AMPK activation and that berteroin might be useful for the prevention, amelioration, and treatment of metabolic diseases, including hepatic steatosis.

Anti-Neuroinflammatory Effects and Mechanism of Action of Fructus ligustri lucidi Extract in BV2 Microglia.

For centuries, Fructus ligustri lucidi (FLL; the fruit of Ligustrum lucidum Aiton or Ligustrum japonicum Thunb.) has been commonly used in traditional Chinese medicine for treating hepatitis and aging-related symptoms and in traditional Korean medicine to detoxify kidneys and the liver. Pharmacological research has shown FLL has antioxidant, anti-inflammatory, anticancer, anti-osteoporosis, and hepatoprotective activities. This study was undertaken to investigate the effects of FLL extract (FLLE) on neuroinflammation. After setting a non-toxic concentration using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] assay data, we investigated the effects of FLLE using Western blotting, cell migration, enzyme-linked immunosorbent assay, a nitric oxide (NO) assay, and immunofluorescence staining in lipopolysaccharide (LPS)-stimulated murine BV2 microglial cells. FLLE was non-toxic to BV2 cells up to a concentration of 500 µg/mL and concentration-dependently inhibited the production of NO and prostaglandin E2 and the protein levels of inducible nitric oxide synthase and cyclooxygenase-2 under LPS-induced inflammatory conditions. It also inhibited the secretion of the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Furthermore, FLLE pretreatment attenuated LPS-induced increases of CD68 (a marker of microglia activation) and suppressed the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) signaling pathways in LPS-stimulated BV2 cells, and significantly increased heme oxygenase (HO)-1 levels. FLLE also reduced the LPS-induced increase in the migratory ability of BV2 cells and the phosphorylation of vascular endothelial growth factor receptor 1. Collectively, FLLE effectively inhibited inflammatory response by suppressing the MAPK and NF-κB signaling pathways and inducing HO-1 in LPS-stimulated BV2 microglial cells. Our findings provide a scientific basis for further study of FLL as a candidate for preventing or alleviating neuroinflammation.

Effects of Ginsenoside Rg3 on Inhibiting Differentiation, Adipogenesis, and ER Stress-Mediated Cell Death in Brown Adipocytes.

OBJECTIVES: Ginsenoside Rg3 (Rg3), a main active component of Panax ginseng, has various therapeutic properties in literatures, and it has been studied for its potential use in obesity control due to its antiadipogenic effects in white adipocytes. However, little is known about its effects on brown adipocytes. METHODS: The mechanisms through which Rg3 inhibits differentiation, adipogenesis, and ER stress-mediated cell death in mouse primary brown adipocytes (MPBAs) are explored. RESULTS: Rg3 significantly induced cytotoxicity in differentiated MPBAs but not in undifferentiated MPBAs. Rg3 treatment downregulated the expression of differentiation and adipogenesis markers and the level of perilipin in MPBAs while upregulating the expression of lipolytic Kruppel-like factor genes. Rg3 also induced lipolysis and efflux of triglycerides from MPBAs and subsequently increased proinflammatory cytokine levels. Notably, Rg3 treatment resulted in elevation of ER stress and proapoptotic markers in MPBAs. CONCLUSIONS: Our results demonstrate that Rg3 is able to selectively exert cytotoxicity in differentiated MPBAs while leaving undifferentiated MPBAs intact, resulting in the induction of ER stress and subsequent cell death in MPBAs via regulation of various genes related to adipocyte differentiation, adipogenesis, lipolysis, and inflammation. These results indicate that further studies on the potential therapeutic applications of Rg3 are warranted.

HS­146, a novel phosphoinositide 3­kinase α inhibitor, induces the apoptosis and inhibits the metastatic ability of human breast cancer cells.

The phosphoinositide 3­kinase (PI3K) signaling pathway plays an important role in human cancer as it regulates critical cellular functions, such as survival, proliferation and metabolism. In the present study, a novel PI3Kα inhibitor (HS­146) was synthesized and its anticancer effects on MCF­7, MDA­MB­231, SKBR3 and BT­474 human breast cancer cell lines were confirmed. HS­146 was found to be most effective in inhibiting the proliferation of MCF­7 cells and in inducing cell cycle arrest in the G0/G1 phase by downregulating cyclin D1, cyclin E, cyclin­dependent kinase (Cdk)2 and Cdk4, and upregulating p21Waf1/Cip1 protein levels in this cell line. The induction of apoptosis by HS­146 was confirmed by DAPI staining and western blot analysis. Cell shrinkage and nuclear condensation, which are typical morphological markers of apoptosis, were increased by HS­146 in the MCF­7 cells in a concentration­dependent manner, and HS­146 also increased the protein expression levels of cleaved poly(ADP­ribose) polymerase (PARP) and decreased the protein expression levels of Mcl­1 and caspase­7. In addition, HS­146 effectively decreased the phosphorylation levels of downstream PI3K effectors, such as Akt, mammalian target of rapamycin (mTOR), glycogen synthase kinase 3ß (GSK3ß), p70S6K1 and eukaryotic translation initiation factor 4E­binding protein 1 (4E­BP1). Hypoxia­inducible factor (HIF)­1α and vascular endothelial growth factor (VEGF) expression were also suppressed by HS­146 under hypoxic conditions, and HS­146 inhibited the migration and invasion of MCF­7 cells in a concentration­dependent manner. On the whole, the findings of the present study suggest that HS­146, a novel PI3Kα inhibitor, may be an effective novel therapeutic candidate that suppresses breast cancer proliferation and metastasis by inhibiting the PI3K/Akt/mTOR pathway.

Moxibustion-Simulating Bipolar Radiofrequency Suppresses Weight Gain and Induces Adipose Tissue Browning via Activation of UCP1 and FGF21 in a Mouse Model of Diet-Induced Obesity.

BACKGROUND: Obesity is a pathological condition associated with various diseases including diabetes, stroke, arthritis, infertility, and heart disease. Moxibustion is widely used to prevent and manage obesity in traditional Asian medicine. We tested our hypothesis that moxibustion-simulating bipolar radiofrequency (M-RF) can suppress total body and white adipose tissue (WAT) weight gain via induction of WAT browning in a mouse model of diet-induced obesity (DIO). METHODS: We designed an M-RF device that could accurately adjust the depth and temperature at which heat stimulation was administered into the abdomen of DIO mice. High-fat-fed male C57BL/6 mice were treated with the M-RF device every two or three days for three weeks. We then harvested WAT and serum from the mice and measured total body and WAT weight, size of adipocytes, mitochondrial contents, features of the dead adipocyte environment, and levels of uncoupling protein 1 (UCP1) and fibroblast growth factor 21 (FGF21). RESULTS: Heat stimulation by M-RF in DIO mice resulted in precise temperature adjustment in the mice abdomen, with variance less than 1°C. Additionally, M-RF stimulation inhibited body and WAT weight gain, resulting in increased formation of beige adipocytes, increased mitochondrial content, and decreased formation of dead adipocytes in WAT. Moreover, treatment of M-RF induced expression of UCP1 and FGF21 in serum and/or epididymal WATs in DIO mice. CONCLUSION: Heat stimulation by M-RF treatment induced upregulation of UCP1 and FGF21 expression in serum and/or WATs, which was correlated with reduced total body and WAT weight gain in DIO mice.

Minimally-Invasive Neural Interface for Distributed Wireless Electrocorticogram Recording Systems.

This paper presents a minimally-invasive neural interface for distributed wireless electrocorticogram (ECoG) recording systems. The proposed interface equips all necessary components for ECoG recording, such as the high performance front-end integrated circuits, a fabricated flexible microelectrode array, and wireless communication inside a miniaturized custom-made platform. The multiple units of the interface systems can be deployed to cover a broad range of the target brain region and transmit signals via a built-in intra-skin communication (ISCOM) module. The core integrated circuit (IC) consists of 16-channel, low-power push-pull double-gated preamplifiers, in-channel successive approximation register analog-to-digital converters (SAR ADC) with a single-clocked bootstrapping switch and a time-delayed control unit, an ISCOM module for wireless data transfer through the skin instead of a power-hungry RF wireless transmitter, and a monolithic voltage/current reference generator to support the aforementioned analog and mixed-signal circuit blocks. The IC was fabricated using 250 nm CMOS processes in an area of 3.2 × 0.9 mm² and achieved the low-power operation of 2.5 µW per channel. Input-referred noise was measured as 5.62 µVrms for 10 Hz to 10 kHz and ENOB of 7.21 at 31.25 kS/s. The implemented system successfully recorded multi-channel neural activities in vivo from a primate and demonstrated modular expandability using the ISCOM with power consumption of 160 µW.

Antioxidant and Anti-Inflammatory Effects of Herbal Formula SC-E3 in Lipopolysaccharide-Stimulated RAW 264.7 Macrophages.

SC-E3 is a novel herbal formula composed of five oriental medicinal herbs that are used to treat a wide range of inflammatory diseases in Korean traditional medicine. In this study, we sought to determine the effects of SC-E3 on free radical generation and inflammatory response in lipopolysaccharide- (LPS-) treated RAW 264.7 macrophages and the molecular mechanism involved. The ethanol extract of SC-E3 showed good free radical scavenging activity and inhibited LPS-induced reactive oxygen species generation. SC-E3 significantly inhibited the production of the LPS-induced inflammatory mediators, nitric oxide and prostaglandin E2, by suppressing the expressions of inducible nitric oxide synthase and cyclooxygenase-2, respectively. SC-E3 also prevented the secretion of the proinflammatory cytokines, IL-1ß, TNF-α, and IL-6, and inhibited LPS-induced NF-κB activation and the mitogen-activated protein kinase (MAPK) pathway. Furthermore, SC-E3 induced the expression of heme oxygenase-1 (HO-1) by promoting the nuclear translocation and transactivation of Nrf2. Taken together, these results suggest that SC-E3 has potent antioxidant and anti-inflammatory effects and that these effects are due to the inhibitions of NF-κB and MAPK and the induction of Nrf2-mediated HO-1 expression in macrophages. These findings provide scientific evidence supporting the potential use of SC-E3 for the treatment and prevention of various inflammatory diseases.

Anticancer Effects of a Korean Herbal Medicine Formula (H9) via AMPK and HER2-PI3K/Akt Signaling in Breast Cancer Cells.

An H9 is a formula of nine medicinal herbs derived from Osuyubujaijung-tang, a traditional Korean prescription for Soeumin constitution. In our previous study, H9 showed anticancer effects against breast cancer and non-small-cell lung cancer. However, the underlying mechanisms of these effects have not yet been elucidated. In this study, we investigated the effects of H9, both alone and in combination with trastuzumab, on breast cancer cells and sought to elucidate the mechanisms involved. H9 suppressed the proliferation of human breast cancer cells, induced arrest of the cell cycle at the G0/G1 phase, and caused mitochondrial dysfunction and apoptosis. In addition, H9 induced the activation of AMPK and inhibited the HER2-PI3K/Akt signaling pathway. Furthermore, H9 attenuated hypoxia-induced HIF-1α and VEGF, resulting in decreased migration and invasion of breast cancer cells. Compared with treatment with either drug alone, co-treatment with H9 and trastuzumab significantly inhibited the growth of BT-474 cells through induction of apoptosis. These results suggest that H9 should be considered as a potent anticancer agent that targets the HER2-PI3K/Akt pathway, and the combination of H9 with trastuzumab should be considered as a new therapeutic regimen for treating breast cancer. Copyright © 2017 John Wiley & Sons, Ltd.

Tryptanthrin Suppresses the Activation of the LPS-Treated BV2 Microglial Cell Line via Nrf2/HO-1 Antioxidant Signaling.

Microglia are the resident macrophages in the central nervous system (CNS) and play essential roles in neuronal homeostasis and neuroinflammatory pathologies. Recently, microglia have been shown to contribute decisively to neuropathologic processes after ischemic stroke. Furthermore, natural compounds have been reported to attenuate inflammation and pathologies associated with neuroinflammation. Tryptanthrin (indolo[2,1-b]quinazoline-6,12-dione) is a phytoalkaloid with known anti-inflammatory effects in cells. In present study, the authors confirmed middle cerebral artery occlusion (MCAO) injury triggers the activation of microglia in brain tissue, and investigated whether tryptanthrin influences the function of mouse murine BV2 microglia under LPS-induced inflammatory conditions in vitro. It was found tryptanthrin protected BV2 microglia cells against LPS-induced inflammation and inhibited the induction of M1 phenotype microglia under inflammatory conditions. In addition, tryptanthrin reduced the production of pro-inflammatory cytokines in BV2 microglia cells via nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) signaling and NF-κB signaling. The authors suggest that tryptanthrin might alleviate the progress of neuropathologies by controlling microglial functions under neuroinflammatory conditions.

Speckle noise reduction in ultrasound images using a discrete wavelet transform-based image fusion technique.

Here, the speckle noise in ultrasonic images is removed using an image fusion-based denoising method. To optimize the denoising performance, each discrete wavelet transform (DWT) and filtering technique was analyzed and compared. In addition, the performances were compared in order to derive the optimal input conditions. To evaluate the speckle noise removal performance, an image fusion algorithm was applied to the ultrasound images, and comparatively analyzed with the original image without the algorithm. As a result, applying DWT and filtering techniques caused information loss and noise characteristics, and did not represent the most significant noise reduction performance. Conversely, an image fusion method applying SRAD-original conditions preserved the key information in the original image, and the speckle noise was removed. Based on such characteristics, the input conditions of SRAD-original had the best denoising performance with the ultrasound images. From this study, the best denoising technique proposed based on the results was confirmed to have a high potential for clinical application.

Acute appendicitis diagnosis using artificial neural networks.

BACKGROUND: Artificial neural networks is one of pattern analyzer method which are rapidly applied on a bio-medical field. OBJECTIVE: The aim of this research was to propose an appendicitis diagnosis system using artificial neural networks (ANNs). METHODS: Data from 801 patients of the university hospital in Dongguk were used to construct artificial neural networks for diagnosing appendicitis and acute appendicitis. A radial basis function neural network structure (RBF), a multilayer neural network structure (MLNN), and a probabilistic neural network structure (PNN) were used for artificial neural network models. The Alvarado clinical scoring system was used for comparison with the ANNs. RESULTS: The accuracy of the RBF, PNN, MLNN, and Alvarado was 99.80%, 99.41%, 97.84%, and 72.19%, respectively. The area under ROC (receiver operating characteristic) curve of RBF, PNN, MLNN, and Alvarado was 0.998, 0.993, 0.985, and 0.633, respectively. CONCLUSIONS: The proposed models using ANNs for diagnosing appendicitis showed good performances, and were significantly better than the Alvarado clinical scoring system (p < 0.001). With cooperation among facilities, the accuracy for diagnosing this serious health condition can be improved.

A PWM Buck Converter With Load-Adaptive Power Transistor Scaling Scheme Using Analog-Digital Hybrid Control for High Energy Efficiency in Implantable Biomedical Systems.

We report a pulse width modulation (PWM) buck converter that is able to achieve a power conversion efficiency (PCE) of > 80% in light loads 100 µA) for implantable biomedical systems. In order to achieve a high PCE for the given light loads, the buck converter adaptively reconfigures the size of power PMOS and NMOS transistors and their gate drivers in accordance with load currents, while operating at a fixed frequency of 1 MHz. The buck converter employs the analog-digital hybrid control scheme for coarse/fine adjustment of power transistors. The coarse digital control generates an approximate duty cycle necessary for driving a given load and selects an appropriate width of power transistors to minimize redundant power dissipation. The fine analog control provides the final tuning of the duty cycle to compensate for the error from the coarse digital control. The mode switching between the analog and digital controls is accomplished by a mode arbiter which estimates the average of duty cycles for the given load condition from limit cycle oscillations (LCO) induced by coarse adjustment. The fabricated buck converter achieved a peak efficiency of 86.3% at 1.4 mA and > 80% efficiency for a wide range of load conditions from 45 µA to 4.1 mA, while generating 1 V output from 2.5-3.3 V supply. The converter occupies 0.375 mm(2) in 0.18 µm CMOS processes and requires two external components: 1.2 µF capacitor and 6.8 µH inductor.

An analysis of contrast agent flow patterns from sequential ultrasound images using a motion estimation algorithm based on optical flow patterns.

This study estimates flow patterns of contrast agents from successive ultrasound image sequences by using an anisotropic diffusion-based optical flow algorithm. Before flow fields were recovered, the test sequences were reconstructed using relative composition of structural and textural parts from the original image. To improve estimation performance, an anisotropic diffusion filtering model was embedded into a spline-based slightly nonconvex total variation-L1 minimization algorithm. In addition, an incremental coarse-to-fine warping framework was employed with a linear minimization scheme to account for a large displacement. After each warping iteration, the implementation used intermediate bilateral filtering to prevent oversmoothing across motion boundaries. The performance of the proposed algorithm was tested using three different sequences obtained from two simulated datasets and phantom ultrasound sequences. The results indicate the robust performance of the proposed method under different noise environments. The results of the phantom study also demonstrate reliable performance according to different injection conditions of contrast agents. These experimental results suggest the potential clinical applicability of the proposed algorithm to ultrasonographic diagnosis based on contrast agents.