A comparative study of predicting the availability of power line communication nodes using machine learning.

Power Line Communication technology uses power cables to transmit data. Knowing whether a node is working in advance without testing saves time and resources, leading to the proposed model. The model has been trained on three dominant features, which are SNR (Signal to Noise Ratio), RSSI (Received Signal Strength Indicator), and CINR (Carrier to Interference plus Noise Ratio). The dataset consisted of 1000 readings, with 90% in the training set and 10% in the testing set. In addition, 50% of the dataset is for class 1, which indicates whether the node readings are optimum. The model is trained with multi-layer perception, K-Nearest Neighbors, Support Vector Machine with linear and non-linear kernels, Random Forest, and adaptive boosting (ADA) algorithms to compare between statistical, vector-based, regression, decision, and predictive algorithms. ADA boost has achieved the best accuracy, F-score, precision, and recall, which are 87%, 0.86613, 0.9, 0.8646, respectively.

The Neural Engine: A Reprogrammable Low Power Platform for Closed-Loop Optogenetics.

Brain-machine Interfaces (BMI) hold great potential for treating neurological disorders such as epilepsy. Technological progress is allowing for a shift from open-loop, pacemaker-class, intervention towards fully closed-loop neural control systems. Low power programmable processing systems are therefore required which can operate within the thermal window of 2° C for medical implants and maintain long battery life. In this work, we have developed a low power neural engine with an optimized set of algorithms which can operate under a power cycling domain. We have integrated our system with a custom-designed brain implant chip and demonstrated the operational applicability to the closed-loop modulating neural activities in in-vitro and in-vivo brain tissues: the local field potentials can be modulated at required central frequency ranges. Also, both a freely-moving non-human primate (24-hour) and a rodent (1-hour) in-vivo experiments were performed to show system reliable recording performance. The overall system consumes only 2.93 mA during operation with a biological recording frequency 50 Hz sampling rate (the lifespan is approximately 56 hours). A library of algorithms has been implemented in terms of detection, suppression and optical intervention to allow for exploratory applications in different neurological disorders. Thermal experiments demonstrated that operation creates minimal heating as well as battery performance exceeding 24 hours on a freely moving rodent. Therefore, this technology shows great capabilities for both neuroscience in-vitro/in-vivo applications and medical implantable processing units.

Xanthomicrol Exerts Antiangiogenic and Antitumor Effects in a Mouse Melanoma (B16F10) Allograft Model.

Xanthomicrol, a trimethoxylated hydroxyflavone, is the main active component of Dracocephalum kotschyi Boiss leaf extract. Preliminary in vitro studies identified this compound as a potential antiangiogenic and anticancer agent. This study aimed to evaluate in vivo anticancer effect of xanthomicrol and investigate its molecular mechanism of action in a mouse melanoma (B16F10) model. Effect of xanthomicrol on B16F10 melanoma cell viability was determined using the MTT assay. For in vivo experiments, C57BL/6 mice were inoculated subcutaneously with B16F10 cells. After five days, once daily administration of xanthomicrol, thalidomide, or vehicle was commenced and continued for 21 consecutive days. On the 26th day, blood samples and tumor biopsies were taken for subsequent molecular analysis. Xanthomicrol showed inhibitory effect on viability of B16F10 melanoma cells (IC50 value: 3.433 µg/ml). Initial tumor growth, tumor volume and weight, and angiogenesis were significantly decreased in xanthomicrol-treated animals compared with those in vehicle group. Protein expression of phosphorylated Akt, mRNA expressions of HIF-1α and VEGF in tumor tissues, and serum VEGF were significantly decreased in xanthomicrol-treated animals compared with vehicle-treated animals. Thus, xanthomicrol inhibited cancer cell growth both in vitro and in vivo. This effect, at least in part, was exerted by interfering with PI3K/Akt signaling pathway and inhibiting VEGF secretion by tumor cells. Further studies are required to elucidate the exact molecular mechanisms of antitumor activity of xanthomicrol.

A current-mode system to self-measure temperature on implantable optoelectronics.

BACKGROUND: One of the major concerns in implantable optoelectronics is the heat generated by emitters such as light emitting diodes (LEDs). Such devices typically produce more heat than light, whereas medical regulations state that the surface temperature change of medical implants must stay below + 2 °C. The LED's reverse current can be employed as a temperature-sensitive parameter to measure the temperature change at the implant's surface, and thus, monitor temperature rises. The main challenge in this approach is to bias the LED with a robust voltage since the reverse current is strongly and nonlinearly sensitive to the bias voltage. METHODS: To overcome this challenge, we have developed an area-efficient LED-based temperature sensor using the LED as its own sensor and a CMOS electronic circuit interface to ensure stable bias and current measurement. The circuit utilizes a second-generation current conveyor (CCII) configuration to achieve this and has been implemented in 0.35 µm CMOS technology. RESULTS: The developed circuits have been experimentally characterized, and the temperature-sensing functionality has been tested by interfacing different mini-LEDs in saline models of tissue prior to in vivo operation. The experimental results show the functionality of the CMOS electronics and the efficiency of the CCII-based technique with an operational frequency up to 130 kHz in achieving a resolution of 0.2 °C for the surface temperature up to + 45 °C. CONCLUSIONS: We developed a robust CMOS current-mode sensor interface which has a reliable CCII to accurately convey the LED's reverse current. It is low power and robust against power supply ripple and transistor mismatch which makes it reliable for sensor interface. The achieved results from the circuit characterization and in vivo experiments show the feasibility of the whole sensor interface in monitoring the tissue surface temperature in optogenetics.

Ultrasound Intra Body Multi Node Communication System for Bioelectronic Medicine.

The coming years may see the advent of distributed implantable devices to support bioelectronic medicinal treatments. Communication between implantable components and between deep implants and the outside world can be challenging. Percutaneous wired connectivity is undesirable and both radiofrequency and optical methods are limited by tissue absorption and power safety limits. As such, there is a significant potential niche for ultrasound communications in this domain. In this paper, we present the design and testing of a reliable and efficient ultrasonic communication telemetry scheme using piezoelectric transducers that operate at 320 kHz frequency. A key challenge results from the multi-propagation path effect. Therefore, we present a method, using short pulse sequences with relaxation intervals. To counter an increasing bit, and thus packet, error rate with distance, we have incorporated an error correction encoding scheme. We then demonstrate how the communication scheme can scale to a network of implantable devices. We demonstrate that we can achieve an effective, error-free, data rate of 0.6 kbps, which is sufficient for low data rate bioelectronic medicine applications. Transmission can be achieved at an energy cost of 642 nJ per bit data packet using on/off power cycling in the electronics.

Wireless Ultrasonic Communication for Biomedical Injectable Implantable Device.

This paper presents a design and implementation of an ultrasonic wireless communication link for an injectable biomedical implanted device. The results address how the ultrasound link encounter from the multiple paths propagation effect. The ultrasound link characterized in term of channel impulse response and power transmission losses against the depth of the implant, the achieved data transmission rate was 70 Kbps and the signal to noise ratio was (30, 35 and 47) dB at a transmission voltage of (1.8, 3.3 and 20) V peak to peak in 12 cm depth. The transmission loss increases as the depth of the implant increases. The ultrasound link represented by two piezoelectric transducers that operate in 320 KHz radial resonance frequency.

Comparison between Different Optical Systems for Optogenetics based Head Mounted Device for Retina Pigmentosa.

Optogenetics is a fast growing neuromodulation techniques as it can remotely stimulate neural activities of a genetically modified cells. The advantage of remotely controlling the neural activity triggered researchers to implement a headset to externally stimulate retina cells for people with retina pigmentosa. The wearable device requires an efficient optical system to focus the transmitted light pattern into the retina surface. In this work, three different lenses; contact lens, folded prism and linear lenses are used to evaluate the headset performance. A 90x90 µLED display is used as a light source and the optical efficiency for each lens is measured for different points over the lens area. Moreover, the impact of each lens on the headset performance in power and processing will be discussed in this work.

A Scalable Optoelectronic Neural Probe Architecture With Self-Diagnostic Capability.

There is a growing demand for the development of new types of implantable optoelectronics to support both basic neuroscience and optogenetic treatments for neurological disorders. Target specification requirements include multi-site optical stimulation, programmable radiance profile, safe operation, and miniaturization. It is also preferable to have a simple serial interface rather than large numbers of control lines. This paper demonstrates an optrode structure comprising of a standard complementary metal-oxide-semiconductor process with 18 optical stimulation drivers. Furthermore, diagnostic sensing circuitry is incorporated to determine the long-term functionality of the photonic elements. A digital control system is incorporated to allow independent multisite control and serial communication with external control units.

A head mounted device stimulator for optogenetic retinal prosthesis.

OBJECTIVE: Our main objective is to demonstrate that compact high radiance gallium nitride displays can be used with conventional virtual reality optics to stimulate an optogenetic retina. Hence, we aim to introduce a non-invasive approach to restore vision for people with conditions such as retinitis pigmentosa where there is a remaining viable communication link between the retina and the visual cortex. APPROACH: We design and implement the headset using a high-density µLED matrix, Raspberry Pi, microcontroller from NXP and virtual reality lens. Then, a test platform is developed to evaluate the performance of the headset and the optical system. Furthermore, image simplification algorithms are used to simplify the scene to be sent to the retina. Moreover, in vivo evaluation of the genetically modified retina response at different light intensity is discussed to prove the reliability of the proposed system. MAIN RESULTS: We demonstrate that in keeping with regulatory guidance, the headset displays need to limit their luminance to 90 kcd m-2. We demonstrate an optical system with 5.75% efficiency which allows for 0.16 mW mm-2 irradiance on the retina within the regulatory guidance, but which is capable of an average peak irradiance of 1.35 mW mm-2. As this is lower than the commonly accepted threshold for channelrhodopsin-2, we demonstrate efficacy through an optical model of an eye onto a biological retina. SIGNIFICANCE: We demonstrate a fully functional 8100-pixel headset system including software/hardware which can operate on a standard consumer battery for periods exceeding a 24 h recharge cycle. The headset is capable of delivering enough light to stimulate the genetically modified retina cells and also keeping the amount of light below the regulation threshold for safety.

On-Probe Neural Interface ASIC for Combined Electrical Recording and Optogenetic Stimulation.

Neuromodulation technologies are progressing from pacemaking and sensory operations to full closed-loop control. In particular, optogenetics-the genetic modification of light sensitivity into neural tissue allows for simultaneous optical stimulation and electronic recording. This paper presents a neural interface application-specified integrated circuit (ASIC) for intelligent optoelectronic probes. The architecture is designed to enable simultaneous optical neural stimulation and electronic recording. It provides four low noise (2.08  µV) recording channels optimized for recording local field potentials (LFPs) (0.1-300 Hz bandwidth, 5 mV range, sampled 10-bit@4 kHz), which are more stable for chronic applications. For stimulation, it provides six independently addressable optical driver circuits, which can provide both intensity (8-bit resolution across a 1.1 mA range) and pulse-width modulation for high-radiance light emitting diodes (LEDs). The system includes a fully digital interface using a serial peripheral interface (SPI) protocol to allow for use with embedded controllers. The SPI interface is embedded within a finite state machine (FSM), which implements a command interpreter that can send out LFP data whilst receiving instructions to control LED emission. The circuit has been implemented in a commercially available 0.35  µm CMOS technology occupying a 1.95 mm 1.10 mm footprint for mounting onto the head of a silicon probe. Measured results are given for a variety of bench-top, in vitro and in vivo experiments, quantifying system performance and also demonstrating concurrent recording and stimulation within relevant experimental models.

Opto-electro-thermal optimization of photonic probes for optogenetic neural stimulation.

Implantable photonic probes are of increasing interest to the field of biophotonics and in particular, optogenetic neural stimulation. Active probes with onboard light emissive elements allow for electronic multiplexing and can be manufactured through existing microelectronics methods. However, as the optogenetics field moves towards clinical practice, an important question arises as to whether such probes will cause excessive thermal heating of the surrounding tissue. Light emitting diodes typically produce more heat than light. The resultant temperature rise of the probe surface therefore needs to be maintained under the regulatory limit of 2°C. This work combines optical and thermal modelling, which have been experimental verified. Analysis has been performed on the effect of probe/emitter geometries, emitter, and radiance requirements. Finally, the effective illumination volume has been calculated within thermal limits for different probe emitter types and required thresholds.

Self-sensing of temperature rises on light emitting diode based optrodes.

OBJECTIVE: This work presents a method to determine the surface temperature of microphotonic medical implants like LEDs. Our inventive step is to use the photonic emitter (LED) employed in an implantable device as its own sensor and develop readout circuitry to accurately determine the surface temperature of the device. APPROACH: There are two primary classes of applications where microphotonics could be used in implantable devices; opto-electrophysiology and fluorescence sensing. In such scenarios, intense light needs to be delivered to the target. As blue wavelengths are scattered strongly in tissue, such delivery needs to be either via optic fibres, two-photon approaches or through local emitters. In the latter case, as light emitters generate heat, there is a potential for probe surfaces to exceed the 2 °C regulatory. However, currently, there are no convenient mechanisms to monitor this in situ. MAIN RESULTS: We present the electronic control circuit and calibration method to monitor the surface temperature change of implantable optrode. The efficacy is demonstrated in air, saline, and brain. SIGNIFICANCE: This paper, therefore, presents a method to utilize the light emitting diode as its own temperature sensor.

A low power flash-FPGA based brain implant micro-system of PID control.

In this paper, we demonstrate that a low power flash FPGA based micro-system can provide a low power programmable interface for closed-loop brain implant inter- faces. The proposed micro-system receives recording local field potential (LFP) signals from an implanted probe, performs closed-loop control using a first order control system, then converts the signal into an optogenetic control stimulus pattern. Stimulus can be implemented through optoelectronic probes. The long term target is for both fundamental neuroscience applications and for clinical use in treating epilepsy. Utilizing our device, closed-loop processing consumes only 14nJ of power per PID cycle compared to 1.52µJ per cycle for a micro-controller implementation. Compared to an application specific digital integrated circuit, flash FPGA's are inherently programmable.

High Density, High Radiance $\mu$ LED Matrix for Optogenetic Retinal Prostheses and Planar Neural Stimulation.

Optical neuron stimulation arrays are important for both in-vitro biology and retinal prosthetic biomedical applications. Hence, in this work, we present an 8100 pixel high radiance photonic stimulator. The chip module vertically combines custom made gallium nitride µ LEDs with a CMOS application specific integrated circuit. This is designed with active pixels to ensure random access and to allow continuous illumination of all required pixels. The µLEDs have been assembled on the chip using a solder ball flip-chip bonding technique which has allowed for reliable and repeatable manufacture. We have evaluated the performance of the matrix by measuring the different factors including the static, dynamic power consumption, the illumination, and the current consumption by each LED. We show that the power consumption is within a range suitable for portable use. Finally, the thermal behavior of the matrix is monitored and the matrix proved to be thermally stable.

The Effect of Noscapine on Oxygen-Glucose Deprivation on Primary Murine Cortical Neurons in High Glucose Condition.

In the present work we set out to investigate the neuroprotective effects of noscapine (0.5-2 µM) in presence of D-glucose on primary murine foetal cortical neurons after oxygen-glucose deprivation/24 h. recovery. Cell viability, nitric oxide production and intracellular calcium ((ca(2+))i) levels were evaluated by MTT assay, the modified Griess method and Fura-2 respectively. 25 and 100 mM D-glucose could, in a concentration dependent manner, improve cell viability and decrease NO production and (ca(2+))i level in neuronal cells after ischemic insult. Moreover, pre-incubation of cells with noscapine, noticeably enhanced protective effects of 25 and 100 mM D-glucose compared to similar conditions without noscapine pre-treatment. In fact, noscapine attenuated NO production in a dose-dependent fashion, after 30 minutes (min) OGD, during high-glucose (HG) condition in cortical neurons. Pretreatment with 2 µM noscapine and 25 or 100 mM D-glucose, was shown to decrease the rise in (ca(2+))i induced by Sodium azide/glucose deprivation (chemical OGD) model. These effects were more pronounced than that of 25 or 100 mM D-glucose alone. The present study demonstrated that the neuroprotective effects of HG before an ischemic insult were augmented by pre-treatment with noscapine. Our results also suggested that the neuroprotection offered by both HG and noscapine involve attenuation of NO production and (ca(2+))i levels stimulated by the experimental ischemia in cortical neurons.

Conjugated Linoleic Acid Stimulates Apoptosis in RH and Tehran Strains of Toxoplasma gondii, in Vitro.

BACKGROUND: The aim of this study was to evaluate the effects of conjugated linoleic acid (CLA) on apoptosis of tachyzoites of T. gondii, RH strain (type I) and the cyst-forming Tehran strain (type II) in vitro. METHODS: Toxoplasma strains were injected into the peritoneal cavity of BALB/c mice. The Tehran strain forms cysts in the brain of mice. Bradyzoites within the cysts are reactivated to proliferative tachyzoites, by dexamethasone. Tachyzoites were aspirated from the peritoneum of infected mice, and the percentage of viable parasites was estimated with trypan blue staining. Tachyzoites were inoculated into HeLa cells cultivated in DMEM medium. Different concentrations of CLA were evaluated on T. gondii in HeLa cells by the tetrazolium (MTT) colorimetric assay. Differentiation between apoptosis and cell death was determined by flow cytometry using Annexin V and propidium iodide (PI) double staining. The statistical analysis performed by GraphPad Prism version 6.00. RESULTS: CLA induces apoptosis in virulent (RH) and avirulent (Tehran) strains of T. gondii. The results of MTT indicated that CLA could decrease the proliferation of tachyzoites of both strains in HeLa cells. CONCLUSION: Conjugated linoleic acid has anti-toxoplasmacidal activity on tachyzoites of T. gondii. Therefore, we recommended further studies on this component in order to achieve a new drug against the parasite.

The inhibitory effect of Acyclovir loaded nano-niosomes against herpes simplex virus type-1 in cell culture.

BACKGROUND: Wide distribution and low half-life of acyclovir has led to a high dose consumption of the drug. Recent studies have shown that encapsulation of acyclovir in nano-carriers can increase effectiveness and decrease its side effects. We investigated the inhibitory effect of acyclovir loaded nano-niosomes against herpes simplex virus type-1 (HSV-1) in cell culture. METHODS: In-vitro cytotoxicity study of empty niosomes (E-N), acyclovir loaded niosomes (ACV-N) and ACV as a free drug against HeLa cell line was performed by MTT assay and the viral titers was tested by TCID50 assay. RESULTS: The results indicated that a significant higher antiviral activity for acyclovir loaded nano-niosomes of about 3 times in comparison with free drug. CONCLUSION: The results of this study revealed ACV-N have a higher antiviral activity compared with free drug; it could be a suitable carrier for delivery of acyclovir in the treatment of HSV-1 infections.

CCII based fractional filters of different orders.

This paper aims to generalize the design of continuous-time filters to the fractional domain with different orders and validates the theoretical results with two different CCII based filters. In particular, the proposed study introduces the generalized formulas for the previous fractional-order analysis of equal orders. The fractional-order filters enhance the design flexibility and prove that the integer-order performance is a very narrow subset from the fractional-order behavior due to the extra degrees of freedom. The general fundamentals of these filters are presented by calculating the maximum and minimum frequencies, the half power frequency and the right phase frequency which are considered a critical issue for the filter design. Different numerical solutions for the generalized fractional order low pass filters with two different fractional order elements are introduced and verified by the circuit simulations of two fractional-order filters: Kerwin-Huelsman-Newcomb (KHN) and Tow-Tomas CCII-based filters, showing great matching.

Skeletal muscle post-conditioning by diazoxide, anti-oxidative and anti-apoptotic mechanisms.

Pretreatment with diazoxide, K(ATP) channel opener, increases tissue tolerance against ischemia reperfusion (IR) injury. In clinical settings pretreatment is rarely an option therefore we evaluated the effect of post-ischemic treatment with diazoxide on skeletal muscle IR injury. Rats were treated with either saline, diazoxide (K(ATP) opener; 40 mg/kg) or 5-hydroxydecanoate (5-HD; mitochondrial K(ATP) inhibitor; 40 mg/kg) after skeletal muscle ischemia (3 h) and reperfusion (6, 24 or 48 h). Tissue contents of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) activities, Bax and Bcl-2 protein expression and muscle histology were determined. Apoptosis was examined (24 and 48 h) after ischemia. IR induced severe histological damage, increased MDA content and Bax expression (24 and 48 h; p < 0.01) and decreased CAT and SOD activities (6 and 24 h, p < 0.01 and 48 h, p < 0.05), with no significant effect on Bcl-2 expression. Diazoxide reversed IR effects on MDA (6 and 24 h; p < 0.05), SOD (6 and 24 h; p < 0.01) and CAT (6 and 48 h, p < 0.05 and 24 h p < 0.01) and tissue damage. Diazoxide also decreased Bax (24 and 48 h; p < 0.05) and increased Bcl-2 protein expression (24 and 48 h; p < 0.01). Post-ischemic treatment with 5-HD had no significant effect on IR injury. Number of apoptotic nuclei in IR and 5-HD treated groups significantly increased (p < 0.001) while diazoxide decreased apoptosis (p < 0.01). The results suggested that post-ischemic treatment with diazoxide decrease oxidative stress in acute phase which modulates expression of apoptotic proteins in the late phase of reperfusion injury. Involvement of KATP channels in this effect require further evaluations.

In vitro selection and characterization of deoxyribonucleic acid aptamers for digoxin.

The low therapeutic index of digoxin necessitates careful monitoring of its serum levels. Most of digoxin immunoassays suffer from interferences with digoxin-like immunoreactive substances. Since aptamers have been shown to be highly specific for their targets, the aim of this study was to develop DNA aptamers for this widely used cardiac glycoside. Digoxin was coated onto the surface of streptavidin magnetic beads. DNA aptamers against digoxin were designed using Systematic Evolution of Ligands by Exponential enrichment method (SELEX) by 11 iterative rounds of incubation of digoxin-coated streptavidin magnetic beads with synthetic DNA library, DNA elution, electrophoresis and PCR amplification. The PCR product was cloned and sequenced. Binding affinity was determined using digoxin-BSA conjugate, coated onto ELISA plate. Inhibitory effect of anti-digoxin aptamer was conducted using isolated guinea-pig atrium. Three aptamers (D1, D2 and D3) were identified. Binding studies of fluorescein-labeled truncated (without primer binding region) D1 and D2 and full length D1 anti-digoxin aptamers were performed and their corresponding dissociation constants values were 8.2×10(-9), 44.0×10(-9) and 17.8×10(-9) M, respectively. This is comparable to what other workers have obtained for interaction of monoclonal antibodies raised against digoxin. There was little difference in binding affinity between full length and truncated anti-digoxin D1 aptamer. D1 anti-digoxin aptamer also inhibited the effects of digoxin on the isolated guinea-pig atrium. D1 anti-digoxin aptamer distinguished between digoxin and ouabain in both tissue study and binding experiments. Our finding indicated that D1 anti-digoxin aptamer can selectively bind to digoxin. Further studies might show its suitability for use in digoxin assays and as a therapeutic agent in life-threatening digoxin toxicity.