A GPS Phase-Locked Loop Performance Metric Based on the Phase Discriminator Output

PubMed Central

Stevanovic, Stefan; Pervan, Boris

2018-01-01

We propose a novel GPS phase-lock loop (PLL) performance metric based on the standard deviation of tracking error (defined as the discriminator’s estimate of the true phase error), and explain its advantages over the popular phase jitter metric using theory, numerical simulation, and experimental results. We derive an augmented GPS phase-lock loop (PLL) linear model, which includes the effect of coherent averaging, to be used in conjunction with this proposed metric. The augmented linear model allows more accurate calculation of tracking error standard deviation in the presence of additive white Gaussian noise (AWGN) as compared to traditional linear models. The standard deviation of tracking error, with a threshold corresponding to half of the arctangent discriminator pull-in region, is shown to be a more reliable/robust measure of PLL performance under interference conditions than the phase jitter metric. In addition, the augmented linear model is shown to be valid up until this threshold, which facilitates efficient performance prediction, so that time-consuming direct simulations and costly experimental testing can be reserved for PLL designs that are much more likely to be successful. The effect of varying receiver reference oscillator quality on the tracking error metric is also considered. PMID:29351250

A digitally implemented phase-locked loop detection scheme for analysis of the phase and power stability of a calibration tone

NASA Technical Reports Server (NTRS)

Densmore, A. C.

1988-01-01

A digital phase-locked loop (PLL) scheme is described which detects the phase and power of a high SNR calibration tone. The digital PLL is implemented in software directly from the given description. It was used to evaluate the stability of the Goldstone Deep Space Station open loop receivers for Radio Science. Included is a derivative of the Allan variance sensitivity of the PLL imposed by additive white Gaussian noise; a lower limit is placed on the carrier frequency.

Phase-locked loop design with fast-digital-calibration charge pump

NASA Astrophysics Data System (ADS)

Wang, San-Fu; Hwang, Tsuen-Shiau; Wang, Jhen-Ji

2016-02-01

A fast-digital-calibration technique is proposed for reducing current mismatch in the charge pump (CP) of a phase-locked loop (PLL). The current mismatch in the CP generates fluctuations, which is transferred to the input of voltage-controlled oscillator (VCO). Therefore, the current mismatch increases the reference spur in the PLL. Improving current match of CP will reduce the reference spur and decrease the static phase offset of PLLs. Moreover, the settling time, ripple and power consumption of the PLL are also improved by the proposed technique. This study evaluated a 2.27-2.88 GHz frequency synthesiser fabricated in TSMC 0.18 μm CMOS 1.8 V process. The tuning range of proposed VCO is about 26%. By using the fast-digital-calibration technique, current mismatch is reduced to lower than 0.97%, and the operation range of the proposed CP is between 0.2 and 1.6 V. The proposed PLL has a total power consumption of 22.57 mW and a settling time of 10 μs or less.

A 4 GHz phase locked loop design in 65 nm CMOS for the Jiangmen Underground Neutrino Observatory detector

NASA Astrophysics Data System (ADS)

Parkalian, N.; Robens, M.; Grewing, C.; Christ, V.; Kruth, A.; Liebau, D.; Muralidharan, P.; Nielinger, D.; Roth, C.; Yegin, U.; Zambanini, A.; van Waasen, S.

2018-02-01

This paper presents a 4 GHz phase locked loop (PLL), which is implemented in a 65 nm standard CMOS process to provide low noise and high frequency sampling clocks for readout electronics to be used in the Jiangmen Underground Neutrino Observatory (JUNO) experiment. Based on the application requirements the target of the design is to find the best compromise between power consumption, area and phase noise for a highly reliable topology. The design implements a novel method for the charge pump that suppresses current mismatch when the PLL is locked. This reduces static phase offset at the inputs of the phase-frequency detector (PFD) that otherwise would introduce spurs at the PLL output. In addition, a technique of amplitude regulation for the voltage controlled oscillator (VCO) is presented to provide low noise and reliable operation. The combination of thin and thick oxide varactor transistors ensures optimum tuning range and linearity over process as well as temperature changes for the VCO without additional calibration steps. The current mismatch at the output of the charge pump for the control voltage at about half the 1 V supply voltage is below 0.3% and static phase offset down to 0.25% is reached. The total PLL consumes 18.5 mW power at 1.8 V supply for the VCO and 1 V supply for the other parts.

Digital simulation of hybrid loop operation in RFI backgrounds.

NASA Technical Reports Server (NTRS)

Ziemer, R. E.; Nelson, D. R.

1972-01-01

A digital computer model for Monte-Carlo simulation of an imperfect second-order hybrid phase-locked loop (PLL) operating in radio-frequency interference (RFI) and Gaussian noise backgrounds has been developed. Characterization of hybrid loop performance in terms of cycle slipping statistics and phase error variance, through computer simulation, indicates that the hybrid loop has desirable performance characteristics in RFI backgrounds over the conventional PLL or the costas loop.

Hopf bifurcation and chaos in a third-order phase-locked loop

NASA Astrophysics Data System (ADS)

Piqueira, José Roberto C.

2017-01-01

Phase-locked loops (PLLs) are devices able to recover time signals in several engineering applications. The literature regarding their dynamical behavior is vast, specifically considering that the process of synchronization between the input signal, coming from a remote source, and the PLL local oscillation is robust. For high-frequency applications it is usual to increase the PLL order by increasing the order of the internal filter, for guarantying good transient responses; however local parameter variations imply structural instability, thus provoking a Hopf bifurcation and a route to chaos for the phase error. Here, one usual architecture for a third-order PLL is studied and a range of permitted parameters is derived, providing a rule of thumb for designers. Out of this range, a Hopf bifurcation appears and, by increasing parameters, the periodic solution originated by the Hopf bifurcation degenerates into a chaotic attractor, therefore, preventing synchronization.

A 65nm CMOS low-power MedRadio-band integer-N cascaded phase-locked loop for implantable medical systems.

PubMed

Wang, Yi-Xiao; Chen, Wei-Ming; Wu, Chung-Yu

2014-01-01

This paper presents a low-power MedRadio-band integer-N phase-locked Loop (PLL) system which is composed of two charge-pump PLLs cascade connected. The PLL provides the operation clock and local carrier signals for an implantable medical electronic system. In addition, to avoid the off-chip crystal oscillator, the 13.56 MHz Industrial, Scientific and Medical (ISM) band signal from the wireless power transmission system is adopted as the input reference signal for the PLL. Ring-based voltage controlled oscillators (VCOs) with current control units are adopted to reduce chip area and power dissipation. The proposed cascaded PLL system is designed and implemented in TSMC 65-nm CMOS technology. The measured jitter for 216.96 MHz signal is 12.23 ps and the phase noise is -65.9 dBc/Hz at 100 kHz frequency offset under 402.926 MHz carrier frequency. The measured power dissipations are 66 μW in the first PLL and 195 μW in the whole system under 1-V supply voltage. The chip area is 0.1088 mm(2) and no off-chip component is required which is suitable for the integration of the implantable medical electronic system.

A low jitter PLL clock used for phase change memory

NASA Astrophysics Data System (ADS)

Xiao, Hong; Houpeng, Chen; Zhitang, Song; Daolin, Cai; Xi, Li

2013-02-01

A fully integrated low-jitter, precise frequency CMOS phase-locked loop (PLL) clock for the phase change memory (PCM) drive circuit is presented. The design consists of a dynamic dual-reset phase frequency detector (PFD) with high frequency acquisition, a novel low jitter charge pump, a CMOS ring oscillator based voltage-controlled oscillator (VCO), a 2nd order passive loop filter, and a digital frequency divider. The design is fabricated in 0.35 μm CMOS technology and consumes 20 mW from a supply voltage of 5 V. In terms of the PCM's program operation requirement, the output frequency range is from 1 to 140 MHz. For the 140 MHz output frequency, the circuit features a cycle-to-cycle jitter of 28 ps RMS and 250 ps peak-to-peak.

Digital-only PLL with adaptive search step

NASA Astrophysics Data System (ADS)

Lin, Ming-Lang; Huang, Shu-Chuan; Liu, Jie-Cherng

2014-06-01

In this paper, an all-digital phase-locked loop (PLL) with adaptively controlled up/down counter serves as the loop filter is presented, and it is implemented on a field-programmable gate array. The detailed circuit of the adaptive up/down counter implementing the adaptive search algorithm is also given, in which the search step for frequency acquisition is adaptively scaled down in half until it is reduced to zero. The phase jitter of the proposed PLL can be lowered, yet keeping with fast lock-in time. Thus, the dilemma between the low phase jitter and fast lock-in time of the traditional PLL can be resolved. Simulation results and circuit implementation show that the locked count, phase jitter and lock-in time of the proposed PLL are consistent with the theoretical predictions.

An estimator-predictor approach to PLL loop filter design

NASA Technical Reports Server (NTRS)

Statman, J. I.; Hurd, W. J.

1986-01-01

An approach to the design of digital phase locked loops (DPLLs), using estimation theory concepts in the selection of a loop filter, is presented. The key concept is that the DPLL closed-loop transfer function is decomposed into an estimator and a predictor. The estimator provides recursive estimates of phase, frequency, and higher order derivatives, while the predictor compensates for the transport lag inherent in the loop. This decomposition results in a straightforward loop filter design procedure, enabling use of techniques from optimal and sub-optimal estimation theory. A design example for a particular choice of estimator is presented, followed by analysis of the associated bandwidth, gain margin, and steady state errors caused by unmodeled dynamics. This approach is under consideration for the design of the Deep Space Network (DSN) Advanced Receiver Carrier DPLL.

Response of an all digital phase-locked loop

NASA Technical Reports Server (NTRS)

Garodnick, J.; Greco, J.; Schilling, D. L.

1974-01-01

An all digital phase-locked loop (DPLL) is designed, analyzed, and tested. Three specific configurations are considered, generating first, second, and third order DPLL's; and it is found, using a computer simulation of a noise spike, and verified experimentally, that of these configurations the second-order system is optimum from the standpoint of threshold extension. This substantiates results obtained for analog PLL's.

Method to suppress DDFS spurious signals in a frequency-hopping synthesizer with DDFS-driven PLL architecture.

PubMed

Kwon, Kun-Sup; Yoon, Won-Sang

2010-01-01

In this paper we propose a method of removing from synthesizer output spurious signals due to quasi-amplitude modulation and superposition effect in a frequency-hopping synthesizer with direct digital frequency synthesizer (DDFS)-driven phase-locked loop (PLL) architecture, which has the advantages of high frequency resolution, fast transition time, and small size. There are spurious signals that depend on normalized frequency of DDFS. They can be dominant if they occur within the PLL loop bandwidth. We suggest that such signals can be eliminated by purposefully creating frequency errors in the developed synthesizer.

Improved PLL For FM Demodulator

NASA Technical Reports Server (NTRS)

Kirkham, Harold; Jackson, Shannon P.

1992-01-01

Phase-locked loop (PLL) for frequency demodulator contains improved frequency-to-voltage converter producing less ripple than conventional phase detector. In improved PLL, phase detector replaced by state estimator, implemented by ramp/sample-and-hold circuit. Intended to reduce noise in receiver of frequency-modulated (FM) telemetry link without sacrificing bandwidth. Also applicable to processing received FM signals.

Study of Interpolated Timing Recovery Phase-Locked Loop with Linearly Constrained Adaptive Prefilter for Higher-Density Optical Disc

NASA Astrophysics Data System (ADS)

Kajiwara, Yoshiyuki; Shiraishi, Junya; Kobayashi, Shoei; Yamagami, Tamotsu

2009-03-01

A digital phase-locked loop (PLL) with a linearly constrained adaptive filter (LCAF) has been studied for higher-linear-density optical discs. LCAF has been implemented before an interpolated timing recovery (ITR) PLL unit in order to improve the quality of phase error calculation by using an adaptively equalized partial response (PR) signal. Coefficient update of an asynchronous sampled adaptive FIR filter with a least-mean-square (LMS) algorithm has been constrained by a projection matrix in order to suppress the phase shift of the tap coefficients of the adaptive filter. We have developed projection matrices that are suitable for Blu-ray disc (BD) drive systems by numerical simulation. Results have shown the properties of the projection matrices. Then, we have designed the read channel system of the ITR PLL with an LCAF model on the FPGA board for experiments. Results have shown that the LCAF improves the tilt margins of 30 gigabytes (GB) recordable BD (BD-R) and 33 GB BD read-only memory (BD-ROM) with a sufficient LMS adaptation stability.

Wide bandwidth phase-locked loop circuit

NASA Technical Reports Server (NTRS)

Koudelka, Robert David (Inventor)

2005-01-01

A PLL circuit uses a multiple frequency range PLL in order to phase lock input signals having a wide range of frequencies. The PLL includes a VCO capable of operating in multiple different frequency ranges and a divider bank independently configurable to divide the output of the VCO. A frequency detector detects a frequency of the input signal and a frequency selector selects an appropriate frequency range for the PLL. The frequency selector automatically switches the PLL to a different frequency range as needed in response to a change in the input signal frequency. Frequency range hysteresis is implemented to avoid operating the PLL near a frequency range boundary.

The charge pump PLL clock generator designed for the 1.56 ns bin size time-to-digital converter pixel array of the Timepix3 readout ASIC

NASA Astrophysics Data System (ADS)

Fu, Y.; Brezina, C.; Desch, K.; Poikela, T.; Llopart, X.; Campbell, M.; Massimiliano, D.; Gromov, V.; Kluit, R.; van Beauzekom, M.; Zappon, F.; Zivkovic, V.

2014-01-01

Timepix3 is a newly developed pixel readout chip which is expected to be operated in a wide range of gaseous and silicon detectors. It is made of 256 × 256 pixels organized in a square pixel-array with 55 μm pitch. Oscillators running at 640 MHz are distributed across the pixel-array and allow for a highly accurate measurement of the arrival time of a hit. This paper concentrates on a low-jitter phase locked loop (PLL) that is located in the chip periphery. This PLL provides a control voltage which regulates the actual frequency of the individual oscillators, allowing for compensation of process, voltage, and temperature variations.

Phase locked loop synchronization for direct detection optical PPM communication systems

NASA Technical Reports Server (NTRS)

Chen, C. C.; Gardner, C. S.

1985-01-01

Receiver timing synchronization of an optical pulse position modulation (PPM) communication system can be achieved using a phase locked loop (PLL) if the photodetector output is properly processed. The synchronization performance is shown to improve with increasing signal power and decreasing loop bandwidth. Bit error rate (BER) of the PLL synchronized PPM system is analyzed and compared to that for the perfectly synchronized system. It is shown that the increase in signal power needed to compensate for the imperfect synchronization is small (less than 0.1 dB) for loop bandwidths less than 0.1% of the slot frequency.

Receiver concepts for data transmission at 10 microns

NASA Astrophysics Data System (ADS)

Scholtz, A. L.; Philipp, H. K.; Leeb, W. R.

1984-05-01

Receivers for digitally modulated CO2 laser signals are compared. Incoherent heterodyne receivers and coherent homodyne setups, including the linear phase locked loop (PLL) receiver, the low intermediate frequency translation loop, and the Costas loop receiver were studied. Experiments covered the homodyne systems, emphasizing the linear PLL receiver. Reliable phase lock of the receiver is achieved at carrier levels as low as 3 nW. Reception of signals phase shift keyed with a data rate of up to 150 Mbit/sec is demonstrated at subnanowatt sideband power levels.

A New Built-in Self Test Scheme for Phase-Locked Loops Using Internal Digital Signals

NASA Astrophysics Data System (ADS)

Kim, Youbean; Kim, Kicheol; Kim, Incheol; Kang, Sungho

Testing PLLs (phase-locked loops) is becoming an important issue that affects both time-to-market and production cost of electronic systems. Though a PLL is the most common mixed-signal building block, it is very difficult to test due to internal analog blocks and signals. In this paper, we propose a new PLL BIST (built-in self test) using the distorted frequency detector that uses only internal digital signals. The proposed BIST does not need to load any analog nodes of the PLL. Therefore, it provides an efficient defect-oriented structural test scheme, reduced area overhead, and improved test quality compared with previous approaches.

An Adaptive INS-Aided PLL Tracking Method for GNSS Receivers in Harsh Environments.

PubMed

Cong, Li; Li, Xin; Jin, Tian; Yue, Song; Xue, Rui

2016-01-23

As the weak link in global navigation satellite system (GNSS) signal processing, the phase-locked loop (PLL) is easily influenced with frequent cycle slips and loss of lock as a result of higher vehicle dynamics and lower signal-to-noise ratios. With inertial navigation system (INS) aid, PLLs' tracking performance can be improved. However, for harsh environments with high dynamics and signal attenuation, the traditional INS-aided PLL with fixed loop parameters has some limitations to improve the tracking adaptability. In this paper, an adaptive INS-aided PLL capable of adjusting its noise bandwidth and coherent integration time has been proposed. Through theoretical analysis, the relation between INS-aided PLL phase tracking error and carrier to noise density ratio (C/N₀), vehicle dynamics, aiding information update time, noise bandwidth, and coherent integration time has been built. The relation formulae are used to choose the optimal integration time and bandwidth for a given application under the minimum tracking error criterion. Software and hardware simulation results verify the correctness of the theoretical analysis, and demonstrate that the adaptive tracking method can effectively improve the PLL tracking ability and integrated GNSS/INS navigation performance. For harsh environments, the tracking sensitivity is increased by 3 to 5 dB, velocity errors are decreased by 36% to 50% and position errors are decreased by 6% to 24% when compared with other INS-aided PLL methods.

Wide tracking range, auto ranging, low jitter phase lock loop for swept and fixed frequency systems

DOEpatents

Kerner, Thomas M.

2001-01-01

The present invention provides a wide tracking range phase locked loop (PLL) circuit that achieves minimal jitter in a recovered clock signal, regardless of the source of the jitter (i.e. whether it is in the source or the transmission media). The present invention PLL has automatic harmonic lockout detection circuitry via a novel lock and seek control logic in electrical communication with a programmable frequency discriminator and a code balance detector. (The frequency discriminator enables preset of a frequency window of upper and lower frequency limits to derive a programmable range within which signal acquisition is effected. The discriminator works in combination with the code balance detector circuit to minimize the sensitivity of the PLL circuit to random data in the data stream). In addition, the combination of a differential loop integrator with the lock and seek control logic obviates a code preamble and guarantees signal acquisition without harmonic lockup. An adaptive cable equalizer is desirably used in combination with the present invention PLL to recover encoded transmissions containing a clock and/or data. The equalizer automatically adapts to equalize short haul cable lengths of coaxial and twisted pair cables or wires and provides superior jitter performance itself. The combination of the equalizer with the present invention PLL is desirable in that such combination permits the use of short haul wires without significant jitter.

GPS/IGS Design Analysis Report. Volume 1

DTIC Science & Technology

1982-11-15

PLL Phase Lock Loop FMPCB Parts, Hateriala, and Processes Control Board PPPL Program Preferred Parts List P14 Pseudo-Rando* Noise PSI Peculiar Support...program preferred ?arts list ( PPPL ). Where ?PPL parts were not obtainable, screening, burn-in, and other tes. were imposed on those parts to assure

Highly sensitive self-complementary DNA nanoswitches triggered by polyelectrolytes

NASA Astrophysics Data System (ADS)

Wu, Jincai; Yu, Feng; Zhang, Zheng; Chen, Yong; Du, Jie; Maruyama, Atsushi

2015-12-01

Dimerization of two homologous strands of genomic DNA/RNA is an essential feature of retroviral replication. Herein we show that a cationic comb-type copolymer (CCC), poly(l-lysine)-graft-dextran, accelerates the dimerization of self-complementary stem-loop DNA, frequently found in functional DNA/RNA molecules, such as aptamers. Furthermore, an anionic polymer poly(sodium vinylsulfonate) (PVS) dissociates CCC from the duplex shortly within a few seconds. Then single stem-loop DNA spontaneously transforms from its dimer. Thus we can easily control the dimer and stem-loop DNA by switching on/off CCC activity. Both polyelectrolytes and DNA concentrations are in the nanomole per liter range. The polyelectrolyte-assisted transconformation and sequences design strategy ensures the reversible state control with rapid response and effective switching under physiologically relevant conditions. A further application of this sensitive assembly is to construct an aptamer-type drug delivery system, bind or release functional molecules responding to its transconformation.Dimerization of two homologous strands of genomic DNA/RNA is an essential feature of retroviral replication. Herein we show that a cationic comb-type copolymer (CCC), poly(l-lysine)-graft-dextran, accelerates the dimerization of self-complementary stem-loop DNA, frequently found in functional DNA/RNA molecules, such as aptamers. Furthermore, an anionic polymer poly(sodium vinylsulfonate) (PVS) dissociates CCC from the duplex shortly within a few seconds. Then single stem-loop DNA spontaneously transforms from its dimer. Thus we can easily control the dimer and stem-loop DNA by switching on/off CCC activity. Both polyelectrolytes and DNA concentrations are in the nanomole per liter range. The polyelectrolyte-assisted transconformation and sequences design strategy ensures the reversible state control with rapid response and effective switching under physiologically relevant conditions. A further application of this sensitive assembly is to construct an aptamer-type drug delivery system, bind or release functional molecules responding to its transconformation. Electronic supplementary information (ESI) available: I. Sequences of DIS25, DIS25-2a and DIS25-3a. II. Structural formula of poly(l-lysine)-graft-dextran (PLL-g-Dex). 1H-NMR spectra of PLL-g-Dex in D2O. III. Gel electrophoretic analysis of dimerization of DIS25 with various N/P ratios. IV. The effect of polyelectrolyte on the fluorescence polarity of TAMRA-labeled duplex. V. UV absorption/Tm profiles of DIS25. VI. Arrhenius plots for spontaneous dissociation of the DIS25 dimer and PLL-g-Dex-assisted dimerization of DIS25.VII. Switching between double stem-loop DIS42 and extended multiplex drived by PLL-g-Dex and PVS. See DOI: 10.1039/c5nr05193b

A single chip 2 Gbit/s clock recovery subsystem for digital communications

NASA Astrophysics Data System (ADS)

Hickling, Ronald M.

A self-contained clock recovery/data resynchronizer phase locked loop (PLL) for use in microwave and fiber optic digital communications has been fabricated using GaAs integrated circuit technology. The IC contains the analog and digital components for the PLL: an edge-triggered phase detector based on a 1.2 GHz phase/frequency comparator, an op amp for creating the loop filter, and a VCO based on a differential source-coupled pair amplifier.

Research on phase locked loop in optical memory servo system

NASA Astrophysics Data System (ADS)

Qin, Liqin; Ma, Jianshe; Zhang, Jianyong; Pan, Longfa; Deng, Ming

2005-09-01

Phase locked loop (PLL) is a closed loop automatic control system, which can track the phase of input signal. It widely applies in each area of electronic technology. This paper research the phase locked loop in optical memory servo area. This paper introduces the configuration of digital phase locked loop (PLL) and phase locked servo system, the control theory, and analyses system's stability. It constructs the phase locked loop experiment system of optical disk spindle servo, which based on special chip. DC motor is main object, this system adopted phase locked servo technique and digital signal processor (DSP) to achieve constant linear velocity (CLV) in controlling optical spindle motor. This paper analyses the factors that affect the stability of phase locked loop in spindle servo system, and discusses the affection to the optical disk readout signal and jitter due to the stability of phase locked loop.

A low power MICS band phase-locked loop for high resolution retinal prosthesis.

PubMed

Yang, Jiawei; Skafidas, Efstratios

2013-08-01

Ultra low power dissipation is essential in retinal prosthesis and many other biomedical implants. Extensive research has been undertaken in designing low power biomedical transceivers, however to date, most effort has been focused on low frequency inductive links. For higher frequency, more robust and more complex applications, such as Medical Implant Communication Service (MICS) band multichannel transceivers, power consumption remains high. This paper explores the design of micro-power data links at 400 MHz for a high resolution retinal prosthesis. By taking advantage of advanced small geometry CMOS technology and precise transistor-level modeling, we successfully utilized subthreshold FET operation, which has been historically limited to low frequency circuits due to the inadequate transistor operating speed in and near weak inversion; we have implemented a low power MICS transceiver. Particularly, a low power, MICS band multichannel phase-locked loop (PLL) that employs a subthreshold voltage controlled oscillator (VCO) and digital synchronous dividers has been implemented on a 65-nm CMOS. A design methodology is presented in detail with the demonstration of EKV model parameters extraction. This PLL provides 600- mVpp quadrature oscillations and exhibits a phase noise of -102 dBc/Hz at 200-kHz offset, while only consuming 430- μW from a 1-V supply. The VCO has a gain (KVCO) of 12 MHz/V and is designed to operate in the near-weak inversion region and consumes 220- μA DC current. The designed PLL has a core area of 0.54 mm(2). It satisfies all specifications of MICS band operation with the advantage of significant reduction in power which is crucial for high resolution retinal prosthesis.

Phase-locked-loop interferometry applied to aspheric testing with a computer-stored compensator.

PubMed

Servin, M; Malacara, D; Rodriguez-Vera, R

1994-05-01

A recently developed technique for continuous-phase determination of interferograms with a digital phase-locked loop (PLL) is applied to the null testing of aspheres. Although this PLL demodulating scheme is also a synchronous or direct interferometric technique, the separate unwrapping process is not explicitly required. The unwrapping and the phase-detection processes are achieved simultaneously within the PLL. The proposed method uses a computer-generated holographic compensator. The holographic compensator does not need to be printed out by any means; it is calculated and used from the computer. This computer-stored compensator is used as the reference signal to phase demodulate a sample interferogram obtained from the asphere being tested. Consequently the demodulated phase contains information about the wave-front departures from the ideal computer-stored aspheric interferogram. Wave-front differences of ~ 1 λ are handled easily by the proposed PLL scheme. The maximum recorded frequency in the template's interferogram as well as in the sampled interferogram are assumed to be below the Nyquist frequency.

Remotely manageable system for stabilizing femtosecond lasers

NASA Astrophysics Data System (ADS)

Cizek, Martin; Hucl, Vaclav; Smid, Radek; Mikel, Bretislav; Lazar, Josef; Cip, Ondrej

2014-05-01

In the field of precise measurement of optical frequencies, laser spectroscopy and interferometric distance surveying the optical frequency synthesizers (femtosecond combs) are used as optical frequency references. They generate thousands of narrow-linewidth coherent optical frequencies at the same time. The spacing of generated components equals to the repetition frequency of femtosecond pulses of the laser. The position of the comb spectrum has a frequency offset that is derived from carrier to envelope frequency difference. The repetition frequency and mentioned frequency offset belong to main controlled parameters of the optical frequency comb. If these frequencies are electronically locked an ultrastable frequency standard (i.e. H-maser, Cs- or Rb- clock), its relative stability is transferred to the optical frequency domain. We present a complete digitally controlled signal processing chain for phase-locked loop (PLL) control of the offset frequency. The setup is able to overcome some dropouts caused by the femtosecond laser non-stabilities (temperature drifts, ripple noise and electricity spikes). It is designed as a two-stage control loop, where controlled offset frequency is permanently monitored by digital signal processing. In case of dropouts of PLL, the frequency-locked loop keeps the controlled frequency in the required limits. The presented work gives the possibility of long-time operation of femtosecond combs which is necessary when the optical frequency stability measurement of ultra-stable lasers is required. The detailed description of the modern solution of the PLL with remote management is presented.

Frequency-Domain Channel Estimation and Equalization for Single Carrier Underwater Acoustic Communications

DTIC Science & Technology

2007-01-01

synchronization ; vm(k) white Gaussian noise with average power σ2. If the Doppler shift f m,k is significant, then it causes the received signal ym(k) to be time ...intersymbol interference (ISI) to extend over 20-300 symbols at a data rate of 2-10 kilosymbols per second. Another obstacle is the time -varying Doppler... synchronization that employs a phase-locked loop (PLL) or delay-locked loop (DLL). However, the DFE and PLL/DLL have to interact in a nonlinear fashion

Ultrahigh-speed clock recovery with optical phase lock loop based on four-wave-mixing in a semiconductor optical amplifier

NASA Astrophysics Data System (ADS)

Kim, Dong Hwan; Kim, Sang Hyuck; Jo, Jae Cheol; Choi, Sang Sam

2000-08-01

A new phase lock loop (PLL) is proposed and demonstrated for clock recovery from 40 Gbps time-division-multiplexed (TDM) optical signal using simple optical phase lock loop circuit. The proposed clock recovery scheme improves the jitter effect in PLL circuit from the clock pulse laser of harmonically-mode locked fiber laser. The cross-correlation component between the optical signal and an optical clock pulse train is detected as a four-wave-mixing (FWM) signal generated in SOA. The lock-in frequency range of the clock recovery is found to be within 10 KHz.

A Phase-Locked Loop Model of the Response of the Postural Control System to Periodic Platform Motion

PubMed Central

Schilling, Robert J.; Robinson, Charles J.

2010-01-01

A phase-locked loop (PLL) model of the response of the postural control system to periodic platform motion is proposed. The PLL model is based on the hypothesis that quiet standing (QS) postural sway can be characterized as a weak sinusoidal oscillation corrupted with noise. Because the signal to noise ratio is quite low, the characteristics of the QS oscillator are not measured directly from the QS sway, instead they are inferred from the response of the oscillator to periodic motion of the platform. When a sinusoidal stimulus is applied, the QS oscillator changes speed as needed until its frequency matches that of the platform, thus achieving phase lock in a manner consistent with a PLL control mechanism. The PLL model is highly effective in representing the frequency, amplitude, and phase shift of the sinusoidal component of the phase-locked response over a range of platform frequencies and amplitudes. Qualitative analysis of the PLL control mechanism indicates that there is a finite range of frequencies over which phase lock is possible, and that the size of this capture range decreases with decreasing platform amplitude. The PLL model was tested experimentally using nine healthy subjects and the results reveal good agreement with a mean phase shift error of 13.7° and a mean amplitude error of 0.8 mm. PMID:20378479

Digital correlation detector for low-cost Omega navigation

NASA Technical Reports Server (NTRS)

Chamberlin, K. A.

1976-01-01

Techniques to lower the cost of using the Omega global navigation network with phase-locked loops (PLL) were developed. The technique that was accepted as being "optimal" is called the memory-aided phase-locked loop (MAPLL) since it allows operation on all eight Omega time slots with one PLL through the implementation of a random access memory. The receiver front-end and the signals that it transmits to the PLL were first described. A brief statistical analysis of these signals was then made to allow a rough comparison between the front-end presented in this work and a commercially available front-end to be made. The hardware and theory of application of the MAPLL were described, ending with an analysis of data taken with the MAPLL. Some conclusions and recommendations were also given.

Expandable and reconfigurable instrument node arrays

NASA Technical Reports Server (NTRS)

Hilliard, Lawrence M. (Inventor); Deshpande, Manohar (Inventor)

2012-01-01

An expandable and reconfigurable instrument node includes a feature detection means and a data processing portion in communication with the feature detection means, the data processing portion configured and disposed to process feature information. The instrument node further includes a phase locked loop (PLL) oscillator in communication with the data processing portion, the PLL oscillator configured and disposed to provide PLL information to the processing portion. The instrument node further includes a single tone transceiver and a pulse transceiver in communication with the PLL oscillator, the single tone transceiver configured and disposed to transmit or receive a single tone for phase correction of the PLL oscillator and the pulse transceiver configured and disposed to transmit and receive signals for phase correction of the PLL oscillator. The instrument node further includes a global positioning (GPA) receiver in communication with the processing portion, the GPS receiver configured and disposed to establish a global position of the instrument node.

SEU/SET Tolerant Phase-Locked Loops

NASA Technical Reports Server (NTRS)

Shuler, Robert L., Jr.

2010-01-01

The phase-locked loop (PLL) is an old and widely used circuit for frequency and phase demodulation, carrier and clock recovery, and frequency synthesis [1]. Its implementations range from discrete components to fully integrated circuits and even to firmware or software. Often the PLL is a highly critical component of a system, as for example when it is used to derive the on-chip clock, but as of this writing no definitive single-event upset (SET)/single-event transient (SET) tolerant PLL circuit has been described. This chapter hopes to rectify that situation, at least in regard to PLLs that are used to generate clocks. Older literature on fault-tolerant PLLs deals with detection of a hard failure, which is recovered by replacement, repair, or manual restart of discrete component systems. Several patents exist along these lines (6349391, 6272647, and 7089442). A newer approach is to harden the parts of a PLL system, to one degree or another, such as by using a voltage-based charge pump or a triple modular redundant (TMR) voted voltage-controlled oscillator (VCO). A more comprehensive approach is to harden by triplication and voting (TMR) all the digital pieces (primarily the divider) of a frequency synthesis PLL, but this still leaves room for errors in the VCO and the loop filter. Instead of hardening or voting pieces of a system, such as a frequency synthesis system (i.e., clock multiplier), we will show how the entire system can be voted. There are two main ways of doing this, each with advantages and drawbacks. We will show how each has advantages in certain areas, depending on the lock acquisition and tracking characteristics of the PLL. Because of this dependency on PLL characteristics, we will briefly revisit the theory of PLLs. But first we will describe the characteristics of voters and their correct application, as some literature does not follow the voting procedure that guarantees elimination of errors. Additionally, we will find that voting clocks is a bit trickier than voting data where an infallible clock is assumed. It is our job here to produce (or recover) that assumed infallible clock!

Binding modes of phosphotriesterase-like lactonase complexed with δ-nonanoic lactone and paraoxon using molecular dynamics simulations.

PubMed

Guan, Shanshan; Zhao, Li; Jin, Hanyong; Shan, Ning; Han, Weiwei; Wang, Song; Shan, Yaming

2017-02-01

Phosphotriesterase-like lactonases (PLLs) have received much attention because of their physical and chemical properties. They may have widespread applications in various fields. For example, they show potential for quorum-sensing signaling pathways and organophosphorus (OP) detoxification in agricultural science. However, the mechanism by which PLLs hydrolyze, which involves OP compounds and lactones and a variety of distinct catalytic efficiencies, has only rarely been explored. In the present study, molecular dynamics (MD) simulations were performed to characterize and contrast the structural dynamics of DrPLL, a member of the PLL superfamily in Deinococcus radiodurans, bound to two substrates, δ-nonanoic lactone and paraoxon. It has been observed that there is a 16-fold increase in the catalytic efficiency of the two mutant strains of DrPLL (F26G/C72I) vs. the wild-type enzyme toward the hydrolysis of paraoxon, but an explanation for this behavior is currently lacking. The analysis of the molecular trajectories of DrPLL bound to δ-nonanoic lactone indicated that lactone-induced conformational changes take place in loop 8, which is near the active site. Binding to paraoxon may lead to conformational displacement of loop 1 residues, which could lead to the deformation of the active site and so trigger the entry of the paraoxon into the active site. The efficiency of the F26G/C72I mutant was increased by decreasing the displacement of loop 1 residues and increasing the flexibility of loop 8 residues. These results provide a molecular-level explanation for the experimental behavior.

Design and performance analysis of generalised integrator-based controller for grid connected PV system

NASA Astrophysics Data System (ADS)

Saxena, Hemant; Singh, Alka; Rai, J. N.

2018-07-01

This article discusses the design and control of a single-phase grid-connected photovoltaic (PV) system. A 5-kW PV system is designed and integrated at the DC link of an H-bridge voltage source converter (VSC). The control of the VSC and switching logic is modelled using a generalised integrator (GI). The use of GI or its variants such as second-order GI have recently evolved for synchronisation and are being used as phase locked loop (PLL) circuits for grid integration. Design of PLL circuits and the use of transformations such as Park's and Clarke's are much easier in three-phase systems. But obtaining in-phase and quadrature components becomes an important and challenging issue in single-phase systems. This article addresses this issue and discusses an altogether different application of GI for the design of compensator based on the extraction of in-phase and quadrature components. GI is frequently used as a PLL; however, in this article, it is not used for synchronisation purposes. A new controller has been designed for a single-phase grid-connected PV system working as a single-phase active compensator. Extensive simulation results are shown for the working of integrated PV system under different atmospheric and operating conditions during daytime as well as night conditions. Experimental results showing the proposed control approach are presented and discussed for the hardware set-up developed in the laboratory.

New spatial diversity equalizer based on PLL

NASA Astrophysics Data System (ADS)

Rao, Wei

2011-10-01

A new Spatial Diversity Equalizer (SDE) based on phase-locked loop (PLL) is proposed to overcome the inter-symbol interference (ISI) and phase rotations simultaneously in the digital communication system. The proposed SDE consists of equal gain combining technique based on a famous blind equalization algorithm constant modulus algorithm (CMA) and a PLL. Compared with conventional SDE, the proposed SDE has not only faster convergence rate and lower residual error but also the ability to recover carrier phase rotation. The efficiency of the method is proved by computer simulation.

Reconstructing a missing link in the evolution of a recently diverged phosphotriesterase by active-site loop remodeling.

PubMed

Afriat-Jurnou, Livnat; Jackson, Colin J; Tawfik, Dan S

2012-08-07

Only decades after the introduction of organophosphate pesticides, bacterial phosphotriesterases (PTEs) have evolved to catalyze their degradation with remarkable efficiency. Their closest known relatives, lactonases, with promiscuous phosphotriasterase activity, dubbed PTE-like lactonases (PLLs), share only 30% sequence identity and also differ in the configuration of their active-site loops. PTE was therefore presumed to have evolved from a yet unknown PLL whose primary activity was the hydrolysis of quorum sensing homoserine lactones (HSLs) (Afriat et al. (2006) Biochemistry 45, 13677-13686). However, how PTEs diverged from this presumed PLL remains a mystery. In this study we investigated loop remodeling as a means of reconstructing a homoserine lactonase ancestor that relates to PTE by few mutational steps. Although, in nature, loop remodeling is a common mechanism of divergence of enzymatic functions, reproducing this process in the laboratory is a challenge. Structural and phylogenetic analyses enabled us to remodel one of PTE's active-site loops into a PLL-like configuration. A deletion in loop 7, combined with an adjacent, highly epistatic, point mutation led to the emergence of an HSLase activity that is undetectable in PTE (k(cat)/K(M) values of up to 2 × 10(4)). The appearance of the HSLase activity was accompanied by only a minor decrease in PTE's paraoxonase activity. This specificity change demonstrates the potential role of bifunctional intermediates in the divergence of new enzymatic functions and highlights the critical contribution of loop remodeling to the rapid divergence of new enzyme functions.

Phase-Locked Loop for Precisely Timed Acoustic Stimulation during Sleep

PubMed Central

Santostasi, Giovanni; Malkani, Roneil; Riedner, Brady; Bellesi, Michele; Tononi, Giulio; Paller, Ken A.; Zee, Phyllis C.

2016-01-01

Background A Brain-Computer Interface could potentially enhance the various benefits of sleep. New Method We describe a strategy for enhancing slow-wave sleep (SWS) by stimulating the sleeping brain with periodic acoustic stimuli that produce resonance in the form of enhanced slow-wave activity in the electroencephalogram (EEG). The system delivers each acoustic stimulus at a particular phase of an electrophysiological rhythm using a Phase-Locked Loop (PLL). Results The PLL is computationally economical and well suited to follow and predict the temporal behavior of the EEG during slow-wave sleep. Comparison with Existing Methods Acoustic stimulation methods may be able to enhance SWS without the risks inherent in electrical stimulation or pharmacological methods. The PLL method differs from other acoustic stimulation methods that are based on detecting a single slow wave rather than modeling slow-wave activity over an extended period of time. Conclusions By providing real-time estimates of the phase of ongoing EEG oscillations, the PLL can rapidly adjust to physiological changes, thus opening up new possibilities to study brain dynamics during sleep. Future application of these methods hold promise for enhancing sleep quality and associated daytime behavior and improving physiologic function. PMID:26617321

Phase-locked loop based on nanoelectromechanical resonant-body field effect transistor

NASA Astrophysics Data System (ADS)

Bartsch, S. T.; Rusu, A.; Ionescu, A. M.

2012-10-01

We demonstrate the room-temperature operation of a silicon nanoelectromechanical resonant-body field effect transistor (RB-FET) embedded into phase-locked loop (PLL). The very-high frequency resonator uses on-chip electrostatic actuation and transistor-based displacement detection. The heterodyne frequency down-conversion based on resistive FET mixing provides a loop feedback signal with high signal-to-noise ratio. We identify key parameters for PLL operation, and analyze the performance of the RB-FET at the system level. Used as resonant mass detector, the experimental frequency stability in the ppm-range translates into sub atto-gram (10-18 g) sensitivity in high vacuum. The feedback and control system are generic and may be extended to other mechanical resonators with transistor properties, such as graphene membranes and carbon nanotubes.

High-accuracy resolver-to-digital conversion via phase locked loop based on PID controller

NASA Astrophysics Data System (ADS)

Li, Yaoling; Wu, Zhong

2018-03-01

The problem of resolver-to-digital conversion (RDC) is transformed into the problem of angle tracking control, and a phase locked loop (PLL) method based on PID controller is proposed in this paper. This controller comprises a typical PI controller plus an incomplete differential which can avoid the amplification of higher-frequency noise components by filtering the phase detection error with a low-pass filter. Compared with conventional ones, the proposed PLL method makes the converter a system of type III and thus the conversion accuracy can be improved. Experimental results demonstrate the effectiveness of the proposed method.

Design of a 2.4-GHz CMOS monolithic fractional-N frequency synthesizer

NASA Astrophysics Data System (ADS)

Shu, Keliu

The wireless communication technology and market have been growing rapidly since a decade ago. The high demand market is a driving need for higher integration in the wireless transceivers. The trend is to achieve low-cost, small form factor and low power consumption. With the ever-reducing feature size, it is becoming feasible to integrate the RF front-end together with the baseband in the low-cost CMOS technology. The frequency synthesizer is a key building block in the RF front-end of the transceivers. It is used as a local oscillator for frequency translation and channel selection. The design of a 2.4-GHz low-power frequency synthesizer in 0.35mum CMOS is a challenging task mainly due to the high-speed prescaler. In this dissertation, a brief review of conventional PLL and frequency synthesizers is provided. Design techniques of a 2.4-GHz monolithic SigmaDelta fractional-N frequency synthesizer are investigated. Novel techniques are proposed to tackle the speed and integration bottlenecks of high-frequency PLL. A low-power and inherently glitch-free phase-switching prescaler and an on-chip loop filter with capacitance multiplier are developed. Compared with the existing and popular dual-path topology, the proposed loop filter reduces circuit complexity and its power consumption and noise are negligible. Furthermore, a third-order three-level digital SigmaDelta modulator topology is employed to reduce the phase noise generated by the modulator. Suitable PFD and charge-pump designs are employed to reduce their nonlinearity effects and thus minimize the folding of the SigmaDelta modulator-shaped phase noise. A prototype of the fractional-N synthesizer together with some standalone building blocks is designed and fabricated in TSMC 0.35mum CMOS through MOSIS. The prototype frequency synthesizer and standalone prescaler and loop filter are characterized. The feasibility and practicality of the proposed prescaler and loop filter are experimentally verified.

Analysis of the PLL phase error in presence of simulated ionospheric scintillation events

NASA Astrophysics Data System (ADS)

Forte, B.

2012-01-01

The functioning of standard phase locked loops (PLL), including those used to track radio signals from Global Navigation Satellite Systems (GNSS), is based on a linear approximation which holds in presence of small phase errors. Such an approximation represents a reasonable assumption in most of the propagation channels. However, in presence of a fading channel the phase error may become large, making the linear approximation no longer valid. The PLL is then expected to operate in a non-linear regime. As PLLs are generally designed and expected to operate in their linear regime, whenever the non-linear regime comes into play, they will experience a serious limitation in their capability to track the corresponding signals. The phase error and the performance of a typical PLL embedded into a commercial multiconstellation GNSS receiver were analyzed in presence of simulated ionospheric scintillation. Large phase errors occurred during scintillation-induced signal fluctuations although cycle slips only occurred during the signal re-acquisition after a loss of lock. Losses of lock occurred whenever the signal faded below the minimumC/N0threshold allowed for tracking. The simulations were performed for different signals (GPS L1C/A, GPS L2C, GPS L5 and Galileo L1). L5 and L2C proved to be weaker than L1. It appeared evident that the conditions driving the PLL phase error in the specific case of GPS receivers in presence of scintillation-induced signal perturbations need to be evaluated in terms of the combination of the minimumC/N0 tracking threshold, lock detector thresholds, possible cycle slips in the tracking PLL and accuracy of the observables (i.e. the error propagation onto the observables stage).

Optimal space communications techniques. [using digital and phase locked systems for signal processing

NASA Technical Reports Server (NTRS)

Schilling, D. L.

1974-01-01

Digital multiplication of two waveforms using delta modulation (DM) is discussed. It is shown that while conventional multiplication of two N bit words requires N2 complexity, multiplication using DM requires complexity which increases linearly with N. Bounds on the signal-to-quantization noise ratio (SNR) resulting from this multiplication are determined and compared with the SNR obtained using standard multiplication techniques. The phase locked loop (PLL) system, consisting of a phase detector, voltage controlled oscillator, and a linear loop filter, is discussed in terms of its design and system advantages. Areas requiring further research are identified.

Small-Signal Dynamic Analysis of LCC-HVDC with STATCOM at the Inverter Busbar

NASA Astrophysics Data System (ADS)

Liu, Dong; Jiang, Wen; Guo, Chunyi; Rehman, Atiq Ur; Zhao, Chengyong

2018-01-01

This paper develops a linearized small-signal dynamic model of a Line-Commutated-Converter based HVDC (LCC-HVDC) system with STATCOM at the inverter busbar, and validates its accuracy by comparing time-domain responses from small-signal model and PSCAD-based simulation results. Considering the potential impact of Phase-Locked-Loop (PLL) parameters on the study system and the close connection of STATCOM and LCC inverter station at AC busbar, this paper investigates the impact of PLL gains and AC voltage control parameters of STATCOM on the system small-signal stability. The studies show that (i) the PLL gain has highly impact on the study system and smaller PLL gains are preferable; (ii) larger values of both the proportional gain and the integral gain of AC voltage controller of STATCOM could result in oscillation/instability of the system.

Optoelectrical clock recovery with dispersion monitoring for high speed transmission

NASA Astrophysics Data System (ADS)

Wen, He; Liao, Jinxin; Zheng, Xiaoping; Zhang, Hanyi; Guo, Yili

2010-12-01

The proposed clock recovery scheme introduces electrooptical modulation to down convert the clock frequency facilitating succeeding narrow band filtering by a phase locked loop (PLL) with ordinary radio frequency (RF) devices, further, employs a quadrature phase detector in the PLL to provide an indication signal for monitoring residual dispersion. It was demonstrated in a polarization multiplexed 160-Gbit/s optical non-return to zero quadrature phase shift keying (NRZ-QPSK) transmission system.

Design of c-band telecontrol transmitter local oscillator for UAV data link

NASA Astrophysics Data System (ADS)

Cao, Hui; Qu, Yu; Song, Zuxun

2018-01-01

A C-band local oscillator of an Unmanned Aerial Vehicle (UAV) data link radio frequency (RF) transmitter unit with high-stability, high-precision and lightweight was designed in this paper. Based on the highly integrated broadband phase-locked loop (PLL) chip HMC834LP6GE, the system performed fractional-N control by internal modules programming to achieve low phase noise and small frequency resolution. The simulation and testing methods were combined to optimize and select the loop filter parameters to ensure the high precision and stability of the frequency synthesis output. The theoretical analysis and engineering prototype measurement results showed that the local oscillator had stable output frequency, accurate frequency step, high spurious suppression and low phase noise, and met the design requirements. The proposed design idea and research method have theoretical guiding significance for engineering practice.

A hybrid analog-digital phase-locked loop for frequency mode non-contact scanning probe microscopy.

PubMed

Mehta, M M; Chandrasekhar, V

2014-01-01

Non-contact scanning probe microscopy (SPM) has developed into a powerful technique to image many different properties of samples. The conventional method involves monitoring the amplitude, phase, or frequency of a cantilever oscillating at or near its resonant frequency as it is scanned across the surface of a sample. For high Q factor cantilevers, monitoring the resonant frequency is the preferred method in order to obtain reasonable scan times. This can be done by using a phase-locked-loop (PLL). PLLs can be obtained as commercial integrated circuits, but these do not have the frequency resolution required for SPM. To increase the resolution, all-digital PLLs requiring sophisticated digital signal processors or field programmable gate arrays have also been implemented. We describe here a hybrid analog/digital PLL where most of the components are implemented using discrete analog integrated circuits, but the frequency resolution is provided by a direct digital synthesis chip controlled by a simple peripheral interface controller (PIC) microcontroller. The PLL has excellent frequency resolution and noise, and can be controlled and read by a computer via a universal serial bus connection.

A hybrid analog-digital phase-locked loop for frequency mode non-contact scanning probe microscopy

NASA Astrophysics Data System (ADS)

Mehta, M. M.; Chandrasekhar, V.

2014-01-01

Non-contact scanning probe microscopy (SPM) has developed into a powerful technique to image many different properties of samples. The conventional method involves monitoring the amplitude, phase, or frequency of a cantilever oscillating at or near its resonant frequency as it is scanned across the surface of a sample. For high Q factor cantilevers, monitoring the resonant frequency is the preferred method in order to obtain reasonable scan times. This can be done by using a phase-locked-loop (PLL). PLLs can be obtained as commercial integrated circuits, but these do not have the frequency resolution required for SPM. To increase the resolution, all-digital PLLs requiring sophisticated digital signal processors or field programmable gate arrays have also been implemented. We describe here a hybrid analog/digital PLL where most of the components are implemented using discrete analog integrated circuits, but the frequency resolution is provided by a direct digital synthesis chip controlled by a simple peripheral interface controller (PIC) microcontroller. The PLL has excellent frequency resolution and noise, and can be controlled and read by a computer via a universal serial bus connection.

PLL jitter reduction by utilizing a ferroelectric capacitor as a VCO timing element.

PubMed

Pauls, Greg; Kalkur, Thottam S

2007-06-01

Ferroelectric capacitors have steadily been integrated into semiconductor processes due to their potential as storage elements within memory devices. Polarization reversal within ferroelectric capacitors creates a high nonlinear dielectric constant along with a hysteresis profile. Due to these attributes, a phase-locked loop (PLL), when based on a ferroelectric capacitor, has the advantage of reduced cycle-to-cycle jitter. PLLs based on ferroelectric capacitors represent a new research area for reduction of oscillator jitter.

Direct Adaptive Rejection of Vortex-Induced Disturbances for a Powered SPAR Platform

NASA Technical Reports Server (NTRS)

VanZwieten, Tannen S.; Balas, Mark J.; VanZwieten, James H.; Driscoll, Frederick R.

2009-01-01

The Rapidly Deployable Stable Platform (RDSP) is a novel vessel designed to be a reconfigurable, stable at-sea platform. It consists of a detachable catamaran and spar, performing missions with the spar extending vertically below the catamaran and hoisting it completely out of the water. Multiple thrusters located along the spar allow it to be actively controlled in this configuration. A controller is presented in this work that uses an adaptive feedback algorithm in conjunction with Direct Adaptive Disturbance Rejection (DADR) to mitigate persistent, vortex-induced disturbances. Given the frequency of a disturbance, the nominal DADR scheme adaptively compensates for its unknown amplitude and phase. This algorithm is extended to adapt to a disturbance frequency that is only coarsely known by including a Phase Locked Loop (PLL). The PLL improves the frequency estimate on-line, allowing the modified controller to reduce vortex-induced motions by more than 95% using achievable thrust inputs.

Phase error statistics of a phase-locked loop synchronized direct detection optical PPM communication system

NASA Technical Reports Server (NTRS)

Natarajan, Suresh; Gardner, C. S.

1987-01-01

Receiver timing synchronization of an optical Pulse-Position Modulation (PPM) communication system can be achieved using a phased-locked loop (PLL), provided the photodetector output is suitably processed. The magnitude of the PLL phase error is a good indicator of the timing error at the receiver decoder. The statistics of the phase error are investigated while varying several key system parameters such as PPM order, signal and background strengths, and PPL bandwidth. A practical optical communication system utilizing a laser diode transmitter and an avalanche photodiode in the receiver is described, and the sampled phase error data are presented. A linear regression analysis is applied to the data to obtain estimates of the relational constants involving the phase error variance and incident signal power.

Compensation of PVT Variations in ToF Imagers with In-Pixel TDC

PubMed Central

Vornicu, Ion; Carmona-Galán, Ricardo; Rodríguez-Vázquez, Ángel

2017-01-01

The design of a direct time-of-flight complementary metal-oxide-semiconductor (CMOS) image sensor (dToF-CIS) based on a single-photon avalanche-diode (SPAD) array with an in-pixel time-to-digital converter (TDC) must contemplate system-level aspects that affect its overall performance. This paper provides a detailed analysis of the impact of process parameters, voltage supply, and temperature (PVT) variations on the time bin of the TDC array. Moreover, the design and characterization of a global compensation loop is presented. It is based on a phase locked loop (PLL) that is integrated on-chip. The main building block of the PLL is a voltage-controlled ring-oscillator (VCRO) that is identical to the ones employed for the in-pixel TDCs. The reference voltage that drives the master VCRO is distributed to the voltage control inputs of the slave VCROs such that their multiphase outputs become invariant to PVT changes. These outputs act as time interpolators for the TDCs. Therefore the compensation scheme prevents the time bin of the TDCs from drifting over time due to the aforementioned factors. Moreover, the same scheme is used to program different time resolutions of the direct time-of-flight (ToF) imager aimed at 3D ranging or depth map imaging. Experimental results that validate the analysis are provided as well. The compensation loop proves to be remarkably effective. The spreading of the TDCs time bin is lowered from: (i) 20% down to 2.4% while the temperature ranges from 0 °C to 100 °C; (ii) 27% down to 0.27%, when the voltage supply changes within ±10% of the nominal value; (iii) 5.2 ps to 2 ps standard deviation over 30 sample chips, due to process parameters’ variation. PMID:28486405

Compensation of PVT Variations in ToF Imagers with In-Pixel TDC.

PubMed

Vornicu, Ion; Carmona-Galán, Ricardo; Rodríguez-Vázquez, Ángel

2017-05-09

The design of a direct time-of-flight complementary metal-oxide-semiconductor (CMOS) image sensor (dToF-CIS) based on a single-photon avalanche-diode (SPAD) array with an in-pixel time-to-digital converter (TDC) must contemplate system-level aspects that affect its overall performance. This paper provides a detailed analysis of the impact of process parameters, voltage supply, and temperature (PVT) variations on the time bin of the TDC array. Moreover, the design and characterization of a global compensation loop is presented. It is based on a phase locked loop (PLL) that is integrated on-chip. The main building block of the PLL is a voltage-controlled ring-oscillator (VCRO) that is identical to the ones employed for the in-pixel TDCs. The reference voltage that drives the master VCRO is distributed to the voltage control inputs of the slave VCROs such that their multiphase outputs become invariant to PVT changes. These outputs act as time interpolators for the TDCs. Therefore the compensation scheme prevents the time bin of the TDCs from drifting over time due to the aforementioned factors. Moreover, the same scheme is used to program different time resolutions of the direct time-of-flight (ToF) imager aimed at 3D ranging or depth map imaging. Experimental results that validate the analysis are provided as well. The compensation loop proves to be remarkably effective. The spreading of the TDCs time bin is lowered from: (i) 20% down to 2.4% while the temperature ranges from 0 °C to 100 °C; (ii) 27% down to 0.27%, when the voltage supply changes within ±10% of the nominal value; (iii) 5.2 ps to 2 ps standard deviation over 30 sample chips, due to process parameters' variation.

Development of high precision digital driver of acoustic-optical frequency shifter for ROG

NASA Astrophysics Data System (ADS)

Zhang, Rong; Kong, Mei; Xu, Yameng

2016-10-01

We develop a high precision digital driver of the acoustic-optical frequency shifter (AOFS) based on the parallel direct digital synthesizer (DDS) technology. We use an atomic clock as the phase-locked loop (PLL) reference clock, and the PLL is realized by a dual digital phase-locked loop. A DDS sampling clock up to 320 MHz with a frequency stability as low as 10-12 Hz is obtained. By constructing the RF signal measurement system, it is measured that the frequency output range of the AOFS-driver is 52-58 MHz, the center frequency of the band-pass filter is 55 MHz, the ripple in the band is less than 1 dB@3MHz, the single channel output power is up to 0.3 W, the frequency stability is 1 ppb (1 hour duration), and the frequency-shift precision is 0.1 Hz. The obtained frequency stability has two orders of improvement compared to that of the analog AOFS-drivers. For the designed binary frequency shift keying (2-FSK) and binary phase shift keying (2-PSK) modulation system, the demodulating frequency of the input TTL synchronous level signal is up to 10 kHz. The designed digital-bus coding/decoding system is compatible with many conventional digital bus protocols. It can interface with the ROG signal detecting software through the integrated drive electronics (IDE) and exchange data with the two DDS frequency-shift channels through the signal detecting software.

Word-Synchronous Optical Sampling of Periodically Repeated OTDM Data Words for True Waveform Visualization

NASA Astrophysics Data System (ADS)

Benkler, Erik; Telle, Harald R.

2007-06-01

An improved phase-locked loop (PLL) for versatile synchronization of a sampling pulse train to an optical data stream is presented. It enables optical sampling of the true waveform of repetitive high bit-rate optical time division multiplexed (OTDM) data words such as pseudorandom bit sequences. Visualization of the true waveform can reveal details, which cause systematic bit errors. Such errors cannot be inferred from eye diagrams and require word-synchronous sampling. The programmable direct-digital-synthesis circuit used in our novel PLL approach allows flexible adaption of virtually any problem-specific synchronization scenario, including those required for waveform sampling, for jitter measurements by slope detection, and for classical eye-diagrams. Phase comparison of the PLL is performed at 10-GHz OTDM base clock rate, leading to a residual synchronization jitter of less than 70 fs.

Research on Robust Control Strategies for VSC-HVDC

NASA Astrophysics Data System (ADS)

Zhu, Kaicheng; Bao, Hai

2018-01-01

In the control system of VSC-HVDC, the phase locked loop provides phase signals to voltage vector control and trigger pulses to generate the required reference phase. The PLL is a typical second-order system. When the system is in unstable state, it will oscillate, make the trigger angle shift, produce harmonic, and make active power and reactive power coupled. Thus, considering the external disturbances introduced by the PLL in VSC-HVDC control system, the parameter perturbations of the controller and the model uncertainties, a H∞ robust controller of mixed sensitivity optimization problem is designed by using the Hinf function provided by the robust control toolbox. Then, compare it with the proportional integral controller through the MATLAB simulation experiment. By contrast, when the H∞ robust controller is added, active and reactive power of the converter station can track the change of reference values more accurately and quickly, and reduce overshoot. When the step change of active and reactive power occurs, mutual influence is reduced and better independent regulation is achieved.

Critique of a Hughes shuttle Ku-band data sampler/bit synchronizer

NASA Technical Reports Server (NTRS)

Holmes, J. K.

1980-01-01

An alternative bit synchronizer proposed for shuttle was analyzed in a noise-free environment by considering the basic operation of the loop via timing diagrams and by linearizing the bit synchronizer as an equivalent, continuous, phased-lock loop (PLL). The loop is composed of a high-frequency phase-frequency detector which is capable of detecting both phase and frequency errors and is used to track the clock, and a bit transition detector which attempts to track the transitions of the data bits. It was determined that the basic approach was a good design which, with proper implementation of the accumulator, up/down counter and logic should provide accurate mid-bit sampling with symmetric bits. However, when bit asymmetry occurs, the bit synchronizer can lock up with a large timing error, yet be quasi-stable (timing will not change unless the clock and bit sequence drift). This will result in incorrectly detecting some bits.

Automatic control of clock duty cycle

NASA Technical Reports Server (NTRS)

Feng, Xiaoxin (Inventor); Roper, Weston (Inventor); Seefeldt, James D. (Inventor)

2010-01-01

In general, this disclosure is directed to a duty cycle correction (DCC) circuit that adjusts a falling edge of a clock signal to achieve a desired duty cycle. In some examples, the DCC circuit may generate a pulse in response to a falling edge of an input clock signal, delay the pulse based on a control voltage, adjust the falling edge of the input clock signal based on the delayed pulse to produce an output clock signal, and adjust the control voltage based on the difference between a duty cycle of the output clock signal and a desired duty cycle. Since the DCC circuit adjusts the falling edge of the clock cycle to achieve a desired duty cycle, the DCC may be incorporated into existing PLL control loops that adjust the rising edge of a clock signal without interfering with the operation of such PLL control loops.

A novel photonic oscillator

NASA Technical Reports Server (NTRS)

Yao, X. S.; Maleki, L.

1995-01-01

We report a novel oscillator for photonic RF systems. This oscillator is capable of generating high-frequency signals up to 70 GHz in both electrical and optical domains and is a special voltage-controlled oscillator with an optical output port. It can be used to make a phase-locked loop (PLL) and perform all functions that a PLL is capable of for photonic systems. It can be synchronized to a reference source by means of optical injection locking, electrical injection locking, and PLL. It can also be self-phase locked and self-injection locked to generate a high-stability photonic RF reference. Its applications include high-frequency reference regeneration and distribution, high-gain frequency multiplication, comb-frequecy and square-wave generation, carrier recovery, and clock recovery. We anticipate that such photonic voltage-controlled oscillators (VCOs) will be as important to photonic RF systems as electrical VCOs are to electrical RF systems.

Illumination-based synchronization of high-speed vision sensors.

PubMed

Hou, Lei; Kagami, Shingo; Hashimoto, Koichi

2010-01-01

To acquire images of dynamic scenes from multiple points of view simultaneously, the acquisition time of vision sensors should be synchronized. This paper describes an illumination-based synchronization method derived from the phase-locked loop (PLL) algorithm. Incident light to a vision sensor from an intensity-modulated illumination source serves as the reference signal for synchronization. Analog and digital computation within the vision sensor forms a PLL to regulate the output signal, which corresponds to the vision frame timing, to be synchronized with the reference. Simulated and experimental results show that a 1,000 Hz frame rate vision sensor was successfully synchronized with 32 μs jitters.

Digital Doppler measurement with spacecraft

NASA Technical Reports Server (NTRS)

Kinman, Peter W.; Hinedi, Sami M.; Labelle, Remi C.; Bevan, Roland P.; Del Castillo, Hector M.; Chong, Dwayne C.

1991-01-01

Digital and analog phase-locked loop (PLL) receivers were operated in parallel, each tracking the residual carrier from a spacecraft. The PLL tracked the downlink carrier and measured its instantaneous phase. This information, combined with a knowledge of the uplink carrier and the transponder ratio, permitted the computation of a Doppler observable. In this way, two separate Doppler measurements were obtained for one observation window. The two receivers agreed on the magnitude of the Doppler effect to within 1 mHz. There was less jitter on the data from the digital receiver. This was due to its smaller noise bandwidth. The demonstration and its results are described.

a Low-Cost Chirped-Pulse Fourier Transform Microwave Spectrometer for Undergraduate Physical Chemistry Lab

NASA Astrophysics Data System (ADS)

Carroll, Brandon; Finneran, Ian; Blake, Geoffrey

2014-06-01

We present the design and construction of a simple and low-cost waveguide chirped pulse Fourier transform microwave (CP-FTMW) spectrometer suitable for gas-phase rotational spectroscopy experiments in undergraduate physical chemistry labs as well as graduate level research. The spectrometer operates with modest bandwidth, using phased locked loop (PLL) microwave sources and a direct digital synthesis (DDS) chirp source, making it an affordable for undergraduate labs. The performance of the instrument is benchmarked by acquiring the pure rotational spectrum of the J = 1 - 0 transition OCS and its isotopologues from 11-12.5 GHz.

Laser Metrology Heterodyne Phase-Locked Loop

NASA Technical Reports Server (NTRS)

Loya, Frank; Halverson, Peter

2009-01-01

A method reduces sensitivity to noise in a signal from a laser heterodyne interferometer. The phase-locked loop (PLL) removes glitches that occur in a zero-crossing detector s output [that can happen if the signal-to-noise ratio (SNR) of the heterodyne signal is low] by the use of an internal oscillator that produces a square-wave signal at a frequency that is inherently close to the heterodyne frequency. It also contains phase-locking circuits that lock the phase of the oscillator to the output of the zero-crossing detector. Because the PLL output is an oscillator signal, it is glitch-free. This enables the ability to make accurate phase measurements in spite of low SNR, creates an immunity to phase error caused by shifts in the heterodyne frequency (i.e. if the target moves causing Doppler shift), and maintains a valid phase even when the signal drops out for brief periods of time, such as when the laser is blocked by a stray object.

Power line interference attenuation in multi-channel sEMG signals: Algorithms and analysis.

PubMed

Soedirdjo, S D H; Ullah, K; Merletti, R

2015-08-01

Electromyogram (EMG) recordings are often corrupted by power line interference (PLI) even though the skin is prepared and well-designed instruments are used. This study focuses on the analysis of some of the recent and classical existing digital signal processing approaches have been used to attenuate, if not eliminate, the power line interference from EMG signals. A comparison of the signal to interference ratio (SIR) of the output signals is presented, for four methods: classical notch filter, spectral interpolation, adaptive noise canceller with phase locked loop (ANC-PLL) and adaptive filter, applied to simulated multichannel monopolar EMG signals with different SIR. The effect of each method on the shape of the EMG signals is also analyzed. The results show that ANC-PLL method gives the best output SIR and lowest shape distortion compared to the other methods. Classical notch filtering is the simplest method but some information might be lost as it removes both the interference and the EMG signals. Thus, it is obvious that notch filter has the lowest performance and it introduces distortion into the resulting signals.

An Integrated Programmable Wide-range PLL for Switching Synchronization in Isolated DC-DC Converters

NASA Astrophysics Data System (ADS)

Fard, Miad

In this thesis, two Phase-Locked-Loop (PLL) based synchronization schemes are introduced and applied to a bi-directional Dual-Active-Bridge (DAB) dc-dc converter with an input voltage up to 80 V switching in the range of 250 kHz to 1 MHz. The two schemes synchronize gating signals across an isolated boundary without the need for an isolator per transistor. The Power Transformer Sensing (PTS) method utilizes the DAB power transformer to indirectly sense switching on the secondary side of the boundary, while the Digital Isolator Sensing (DIS) method utilizes a miniature transformer for synchronization and communication at up to 100 MHz. The PLL is implemented on-chip, and is used to control an external DAB power-stage. This work will lead to lower cost, high-frequency isolated dc-dc converters needed for a wide variety of emerging low power applications where isolator cost is relatively high and there is a demand for the reduction of parts.

S-Band POSIX Device Drivers for RTEMS

NASA Technical Reports Server (NTRS)

Lux, James P.; Lang, Minh; Peters, Kenneth J.; Taylor, Gregory H.

2011-01-01

This is a set of POSIX device driver level abstractions in the RTEMS RTOS (Real-Time Executive for Multiprocessor Systems real-time operating system) to SBand radio hardware devices that have been instantiated in an FPGA (field-programmable gate array). These include A/D (analog-to-digital) sample capture, D/A (digital-to-analog) sample playback, PLL (phase-locked-loop) tuning, and PWM (pulse-width-modulation)-controlled gain. This software interfaces to Sband radio hardware in an attached Xilinx Virtex-2 FPGA. It uses plug-and-play device discovery to map memory to device IDs. Instead of interacting with hardware devices directly, using direct-memory mapped access at the application level, this driver provides an application programming interface (API) offering that easily uses standard POSIX function calls. This simplifies application programming, enables portability, and offers an additional level of protection to the hardware. There are three separate device drivers included in this package: sband_device (ADC capture and DAC playback), pll_device (RF front end PLL tuning), and pwm_device (RF front end AGC control).

Design of Dual-Mode Local Oscillators Using CMOS Technology for Motion Detection Sensors.

PubMed

Ha, Keum-Won; Lee, Jeong-Yun; Kim, Jeong-Geun; Baek, Donghyun

2018-04-01

Recently, studies have been actively carried out to implement motion detecting sensors by applying radar techniques. Doppler radar or frequency-modulated continuous wave (FMCW) radar are mainly used, but each type has drawbacks. In Doppler radar, no signal is detected when the movement is stopped. Also, FMCW radar cannot function when the detection object is near the sensor. Therefore, by implementing a single continuous wave (CW) radar for operating in dual-mode, the disadvantages in each mode can be compensated for. In this paper, a dual mode local oscillator (LO) is proposed that makes a CW radar operate as a Doppler or FMCW radar. To make the dual-mode LO, a method that controls the division ratio of the phase locked loop (PLL) is used. To support both radar mode easily, the proposed LO is implemented by adding a frequency sweep generator (FSG) block to a fractional-N PLL. The operation mode of the LO is determined by according to whether this block is operating or not. Since most radar sensors are used in conjunction with microcontroller units (MCUs), the proposed architecture is capable of dual-mode operation by changing only the input control code. In addition, all components such as VCO, LDO, and loop filter are integrated into the chip, so complexity and interface issues can be solved when implementing radar sensors. Thus, the proposed dual-mode LO is suitable as a radar sensor.

Design of Dual-Mode Local Oscillators Using CMOS Technology for Motion Detection Sensors

PubMed Central

Lee, Jeong-Yun; Kim, Jeong-Geun

2018-01-01

Recently, studies have been actively carried out to implement motion detecting sensors by applying radar techniques. Doppler radar or frequency-modulated continuous wave (FMCW) radar are mainly used, but each type has drawbacks. In Doppler radar, no signal is detected when the movement is stopped. Also, FMCW radar cannot function when the detection object is near the sensor. Therefore, by implementing a single continuous wave (CW) radar for operating in dual-mode, the disadvantages in each mode can be compensated for. In this paper, a dual mode local oscillator (LO) is proposed that makes a CW radar operate as a Doppler or FMCW radar. To make the dual-mode LO, a method that controls the division ratio of the phase locked loop (PLL) is used. To support both radar mode easily, the proposed LO is implemented by adding a frequency sweep generator (FSG) block to a fractional-N PLL. The operation mode of the LO is determined by according to whether this block is operating or not. Since most radar sensors are used in conjunction with microcontroller units (MCUs), the proposed architecture is capable of dual-mode operation by changing only the input control code. In addition, all components such as VCO, LDO, and loop filter are integrated into the chip, so complexity and interface issues can be solved when implementing radar sensors. Thus, the proposed dual-mode LO is suitable as a radar sensor. PMID:29614777

Phase-locked loops and their application

NASA Technical Reports Server (NTRS)

Lindsey, W. C. (Editor); Simon, M. K.

1978-01-01

A collection of papers is presented on the characteristics and capabilities of phase-locked loops (PLLs), along with some applications of interest. The discussion covers basic theory (linear and nonlinear); acquisition; threshold; stability; frequency demodulation and detection; tracking; cycle slipping and loss of lock; phase-locked oscillators; operation and performance in the presence of noise; AGC, AFC, and APC circuits and systems; digital PLL; and applications and miscellaneous. With the rapid development of IC technology, PLLs are expected to be used widely in consumer electronics.

A monolithic K-band phase-locked loop for microwave radar application

NASA Astrophysics Data System (ADS)

Zhou, Guangyao; Ma, Shunli; Li, Ning; Ye, Fan; Ren, Junyan

2017-02-01

A monolithic K-band phase-locked loop (PLL) for microwave radar application is proposed and implemented in this paper. By eliminating the tail transistor and using optimized high-Q LC-tank, the proposed voltage-controlled oscillator (VCO) achieves a tuning range of 18.4 to 23.3 GHz and reduced phase noise. Two cascaded current-mode logic (CML) divide-by-two frequency prescalers are implemented to bridge the frequency gap, in which inductor peaking technique is used in the first stage to further boost allowable input frequency. Six-stage TSPC divider chain is used to provide programmable division ratio from 64 to 127, and a second-order passive loop filter with 825 kHz bandwidth is also integrated on-chip to minimize required external components. The proposed PLL needs only approximately 18.2 μs settling time, and achieves a wide tuning range from 18.4 to 23.3 GHz, with a typical output power of ‑0.84 dBm and phase noise of ‑91.92 dBc/Hz @ 1 MHz. The chip is implemented in TSMC 65 nm CMOS process, and occupies an area of 0.56 mm2 without pads under a 1.2 V single voltage supply. Project supported by the National High-Tech Research and Development Program of China (No. 2013AA014101).

Modeling and Simulation of a DG-Integrated Intelligent Microgrid

DTIC Science & Technology

2010-02-01

17. The I-V curve from the manufacturer for BP-4175 175W PV module...........................32   Fig. 18. Wind turbine model...33   Fig. 19. Electrical outputs of wind turbine... PMSG : Permanent Magnet Synchronous Generator PLL : Phase Lock Loop PV : Photovoltaic PWM : Pulse Width Modulation TOU : Time of Use VTES

Multifunctional Triblock Nanocarrier (PAMAM-PEG-PLL) for the Efficient Intracellular siRNA Delivery and Gene Silencing

PubMed Central

2011-01-01

A novel triblock poly(amido amine)-poly(ethylene glycol)-poly-l-lysine (PAMAM-PEG-PLL) nanocarrier was designed, synthesized, and evaluated for the delivery of siRNA. The design of the nanocarrier is unique and provides a solution to most of the common problems associated with the delivery and therapeutic applications of siRNA. Every component in the triblock nanocarrier plays a significant role and performs multiple functions: (1) tertiary amine groups in the PAMAM dendrimer work as a proton sponge and play a vital role in the endosomal escape and cytoplasmic delivery of siRNA; (2) PEG, a linker connecting PLL and PAMAM dendrimers renders nuclease stability and protects siRNA in human plasma; (3) PLL provides primary amines to form polyplexes with siRNA through electrostatic interaction and also acts as penetration enhancer; and (4) conjugation to PEG and PAMAM reduced toxicity of PLL and the entire triblock nanocarrier PAMAM-PEG-PLL. The data obtained show that the polyplexes resulted from the conjugation of siRNA, and the proposed nanocarriers were effectively taken up by cancer cells and induced the knock down of the target BCL2 gene. In addition, triblock nanocarrier/siRNA polyplexes showed excellent stability in human plasma. PMID:21322531

Free-running waveform characterization using a delay-time tunable laser based delay-line-free electro-optic sampling oscilloscope

NASA Astrophysics Data System (ADS)

Lin, Gong-Ru

2002-12-01

We develop a delay-line-free and frequency traceable electro-optic sampling oscilloscope by use of a digital phase-locked loop phase shifter (PLL-PS) controlled delay-time-tunable gain-switched laser diode (GSLD). The home-made voltage-controllable PLL-PS exhibits a linear transfer function with ultra-wide phase shifting range of ±350° and tuning error of <±5%, which benefits the advantages of frequency tracking to free-running signals with suppressed timing-jitter. The maximum delay-time of PLL-PS controlled GSLD is up to 1.95 periods by changing the controlling voltage ( VREF) from -3.5 to 3.5 V, which corresponds to 3.9 ns at repetition frequency of 500 MHz. The tuning responsivity and resolution are about 0.56 ns/V and 0.15˜0.2 ps, respectively. The maximum delay-time switching bandwidth of 100 Hz is determined under the control of a saw-tooth modulated VREF function. The waveform sampling of microwave PECL signals generated from a free-running digital frequency divider is performed with acceptable measuring deviation.

PLL application research of a broadband MEMS phase detector: Theory, measurement and modeling

NASA Astrophysics Data System (ADS)

Han, Juzheng; Liao, Xiaoping

2017-06-01

This paper evaluates the capability of a broadband MEMS phase detector in the application of phase locked loops (PLLs) through the aspect of theory, measurement and modeling. For the first time, it demonstrates how broadband property and optimized structure are realized through cascaded transmission lines and ANSYS simulations. The broadband MEMS phase detector shows potential in PLL application for its dc voltage output and large power handling ability which is important for munition applications. S-parameters of the power combiner in the MEMS phase detector are measured with S11 better than -15 dB and S23 better than -10 dB over the whole X-band. Compared to our previous works, developed phase detection measurements are performed and focused on signals at larger power levels up to 1 W. Cosine tendencies are revealed between the output voltage and the phase difference for both small and large signals. Simulation approach through equivalent circuit modeling is proposed to study the PLL application of the broadband MEMS phase detector. Synchronization and tracking properties are revealed.

High-speed clock recovery with phase-locked-loop-based on LiNbO3 modulators

NASA Astrophysics Data System (ADS)

Zhu, Guanghao; Chen, Hongmin; Wang, Qiang; Dutta, Niloy K.

2003-08-01

In this paper, we present a scheme for recovering 10 GHz clock from 40 Gb/s and 80 Gb/s time division multiplexed (TDM) return to zero (RZ) data stream. The proposed clock recovery is successfully demonstrated using an electrical phase locked loop (PLL). The jitter of the recovered clock is estimated to be around 50 fs. The key part in the proposed clock recovery circuit is a LiNbO3 Mach-Zehnder modulator which is shown to be highly effective in optical to electrical down conversion.

A closed-loop system for frequency tracking of piezoresistive cantilever sensors

NASA Astrophysics Data System (ADS)

Wasisto, Hutomo Suryo; Zhang, Qing; Merzsch, Stephan; Waag, Andreas; Peiner, Erwin

2013-05-01

A closed loop circuit capable of tracking resonant frequencies for MEMS-based piezoresistive cantilever resonators is developed in this work. The proposed closed-loop system is mainly based on a phase locked loop (PLL) circuit. In order to lock onto the resonant frequency of the resonator, an actuation signal generated from a voltage-controlled oscillator (VCO) is locked to the phase of the input reference signal of the cantilever sensor. In addition to the PLL component, an instrumentation amplifier and an active low pass filter (LPF) are connected to the system for gaining the amplitude and reducing the noise of the cantilever output signals. The LPF can transform a rectangular signal into a sinusoidal signal with voltage amplitudes ranging from 5 to 10 V which are sufficient for a piezoactuator input (i.e., maintaining a large output signal of the cantilever sensor). To demonstrate the functionality of the system, a self-sensing silicon cantilever resonator with a built-in piezoresistive Wheatstone bridge is fabricated and integrated with the circuit. A piezoactuator is utilized for actuating the cantilever into resonance. Implementation of this closed loop system is used to track the resonant frequency of a silicon cantilever-based sensor resonating at 9.4 kHz under a cross-sensitivity test of ambient temperature. The changes of the resonant frequency are interpreted using a frequency counter connected to the system. From the experimental results, the temperature sensitivity and coefficient of the employed sensor are 0.3 Hz/°C and 32.8 ppm/°C, respectively. The frequency stability of the system can reach up to 0.08 Hz. The development of this system will enable real-time nanoparticle monitoring systems and provide a miniaturization of the instrumentation modules for cantilever-based nanoparticle detectors.

In vitro and in vivo protein release and anti-ischemia/reperfusion injury properties of bone morphogenetic protein-2-loaded glycyrrhetinic acid-poly(ethylene glycol)-b-poly(l-lysine) nanoparticles

PubMed Central

Shan, Fang; Liu, YuJuan; Jiang, Haiying; Tong, Fei

2017-01-01

Here, we describe a bone morphogenetic protein-2 (BMP-2) nanocarrier based on glycyrrhetinic acid (GA)-poly(ethylene glycol) (PEG)-b-poly(l-lysine) (PLL). A protein nanocarrier was synthesized, characterized and evaluated as a BMP-2 delivery system. The designed nanocarrier was synthesized based on the ring-opening polymerization of amino acid N-carboxyanhydride. The final product was measured with 1H nuclear magnetic resonance. GA-PEG-b-PLL nanocarrier could combine with BMP-2 through electrostatic interaction to form polyion complex (PIC) micelles. BMP-2 could be rapidly and efficiently encapsulated through the GA-PEG-b-PLL nanocarrier under physiological conditions, exhibiting efficient encapsulation and sustained release. In addition, the GA-PEG-b-PLL-mediated BMP-2 delivery system could target the liver against hepatic diseases as it has GA-binding receptors. The anti-hepatic ischemia/reperfusion injury (anti-HI/RI) effect of BMP-2/GA-PEG-b-PLL PIC micelles was investigated in rats using free BMP-2 and BMP-2/PEG-b-PLL PIC micelles as controls, and the results showed that BMP-2/GA-PEG-b-PLL PIC micelles indicated significantly enhanced anti-HI/RI property compared to BMP-2 and BMP-2/PEG-b-PLL. All results suggested that GA-PEG-b-PLL could be used as a potential BMP-2 nanocarrier. PMID:29089759

A low-noise delta-sigma phase modulator for polar transmitters.

PubMed

Zhou, Bo

2014-01-01

A low-noise phase modulator, using finite-impulse-response (FIR) filtering embedded delta-sigma (ΔΣ) fractional-N phase-locked loop (PLL), is fabricated in 0.18 μ m CMOS for GSM/EDGE polar transmitters. A simplified digital compensation filter with inverse-FIR and -PLL features is proposed to trade off the transmitter noise and linearity. Experimental results show that the presented architecture performs RF phase modulation well with 20 mW power dissipation from 1.6 V supply and achieves the root-mean-square (rms) and peak phase errors of 4° and 8.5°, respectively. The measured and simulated phase noises of -104 dBc/Hz and -120 dBc/Hz at 400-kHz offset from 1.8-GHz carrier frequency are observed, respectively.

Modeling and Development of INS-Aided PLLs in a GNSS/INS Deeply-Coupled Hardware Prototype for Dynamic Applications

PubMed Central

Zhang, Tisheng; Niu, Xiaoji; Ban, Yalong; Zhang, Hongping; Shi, Chuang; Liu, Jingnan

2015-01-01

A GNSS/INS deeply-coupled system can improve the satellite signals tracking performance by INS aiding tracking loops under dynamics. However, there was no literature available on the complete modeling of the INS branch in the INS-aided tracking loop, which caused the lack of a theoretical tool to guide the selections of inertial sensors, parameter optimization and quantitative analysis of INS-aided PLLs. This paper makes an effort on the INS branch in modeling and parameter optimization of phase-locked loops (PLLs) based on the scalar-based GNSS/INS deeply-coupled system. It establishes the transfer function between all known error sources and the PLL tracking error, which can be used to quantitatively evaluate the candidate inertial measurement unit (IMU) affecting the carrier phase tracking error. Based on that, a steady-state error model is proposed to design INS-aided PLLs and to analyze their tracking performance. Based on the modeling and error analysis, an integrated deeply-coupled hardware prototype is developed, with the optimization of the aiding information. Finally, the performance of the INS-aided PLLs designed based on the proposed steady-state error model is evaluated through the simulation and road tests of the hardware prototype. PMID:25569751

Instantaneous power control of a high speed permanent magnet synchronous generator based on a sliding mode observer and a phase locked loop

NASA Astrophysics Data System (ADS)

Duan, Jiandong; Fan, Shaogui; Wu, Fengjiang; Sun, Li; Wang, Guanglin

2018-06-01

This paper proposes an instantaneous power control method for high speed permanent magnet synchronous generators (PMSG), to realize the decoupled control of active power and reactive power, through vector control based on a sliding mode observer (SMO), and a phase locked loop (PLL). Consequently, the high speed PMSG has a high internal power factor, to ensure efficient operation. Vector control and accurate estimation of the instantaneous power require an accurate estimate of the rotor position. The SMO is able to estimate the back electromotive force (EMF). The rotor position and speed can be obtained using a combination of the PLL technique and the phase compensation method. This method has the advantages of robust operation, and being resistant to noise when estimating the position of the rotor. Using instantaneous power theory, the relationship between the output active power, reactive power, and stator current of the PMSG is deduced, and the power constraint condition is analysed for operation at the unit internal power factor. Finally, the accuracy of the rotor position detection, the instantaneous power detection, and the control methods are verified using simulations and experiments.

Identification of nonlinear modes using phase-locked-loop experimental continuation and normal form

NASA Astrophysics Data System (ADS)

Denis, V.; Jossic, M.; Giraud-Audine, C.; Chomette, B.; Renault, A.; Thomas, O.

2018-06-01

In this article, we address the model identification of nonlinear vibratory systems, with a specific focus on systems modeled with distributed nonlinearities, such as geometrically nonlinear mechanical structures. The proposed strategy theoretically relies on the concept of nonlinear modes of the underlying conservative unforced system and the use of normal forms. Within this framework, it is shown that without internal resonance, a valid reduced order model for a nonlinear mode is a single Duffing oscillator. We then propose an efficient experimental strategy to measure the backbone curve of a particular nonlinear mode and we use it to identify the free parameters of the reduced order model. The experimental part relies on a Phase-Locked Loop (PLL) and enables a robust and automatic measurement of backbone curves as well as forced responses. It is theoretically and experimentally shown that the PLL is able to stabilize the unstable part of Duffing-like frequency responses, thus enabling its robust experimental measurement. Finally, the whole procedure is tested on three experimental systems: a circular plate, a chinese gong and a piezoelectric cantilever beam. It enable to validate the procedure by comparison to available theoretical models as well as to other experimental identification methods.

Phase locking of a 1.5 Terahertz quantum cascade laser and use as a local oscillator in a heterodyne HEB receiver.

PubMed

Rabanus, D; Graf, U U; Philipp, M; Ricken, O; Stutzki, J; Vowinkel, B; Wiedner, M C; Walther, C; Fischer, M; Faist, J

2009-02-02

We demonstrate for the first time the closure of an electronic phase lock loop for a continuous-wave quantum cascade laser (QCL) at 1.5 THz. The QCL is operated in a closed cycle cryo cooler. We achieved a frequency stability of better than 100 Hz, limited by the resolution bandwidth of the spectrum analyser. The PLL electronics make use of the intermediate frequency (IF) obtained from a hot electron bolometer (HEB) which is downconverted to a PLL IF of 125 MHz. The coarse selection of the longitudinal mode and the fine tuning is achieved via the bias voltage of the QCL. Within a QCL cavity mode, the free-running QCL shows frequency fluctuations of about 5 MHz, which the PLL circuit is able to control via the Stark-shift of the QCL gain material. Temperature dependent tuning is shown to be nonlinear, and of the order of -16 MHz/K. Additionally we have used the QCL as local oscillator (LO) to pump an HEB and perform, again for the first time at 1.5 THz, a heterodyne experiment, and obtain a receiver noise temperature of 1741 K.

A Low-Noise Delta-Sigma Phase Modulator for Polar Transmitters

PubMed Central

Zhou, Bo

2014-01-01

A low-noise phase modulator, using finite-impulse-response (FIR) filtering embedded delta-sigma (ΔΣ) fractional-N phase-locked loop (PLL), is fabricated in 0.18 μm CMOS for GSM/EDGE polar transmitters. A simplified digital compensation filter with inverse-FIR and -PLL features is proposed to trade off the transmitter noise and linearity. Experimental results show that the presented architecture performs RF phase modulation well with 20 mW power dissipation from 1.6 V supply and achieves the root-mean-square (rms) and peak phase errors of 4° and 8.5°, respectively. The measured and simulated phase noises of −104 dBc/Hz and −120 dBc/Hz at 400-kHz offset from 1.8-GHz carrier frequency are observed, respectively. PMID:24719578

Design and analysis of an energy-efficient O-QPSK coherent IR-UWB transceiver with a 0.52° RMS phase-noise fractional synthesizer

NASA Astrophysics Data System (ADS)

Ying, Yutong; Lin, Fujiang; Bai, Xuefei

2018-03-01

This paper explores an energy-efficient pulsed ultra-wideband (UWB) radio-frequency (RF) front-end chip fabricated in 0.18-μm CMOS technology, including a transmitter, receiver, and fractional synthesizer. The transmitter adopts a digital offset quadrature phase-shift keying (O-QPSK) modulator and passive direct-phase multiplexing technology, which are energy- and hardware-efficient, to enhance the data rate for a given spectrum. A passive mixer and a capacitor cross-coupled (CCC) source-follower driving amplifier (DA) are also designed for the transmitter to further reduce the low power consumption. For the receiver, a power-aware low-noise amplifier (LNA) and a quadrature mixer are applied. The LNA adopts a CCC boost common-gate amplifier as the input stage, and its current is reused for the second stage to save power. The mixer uses a shared amplification stage for the following passive IQ mixer. Phase noise suppression of the phase-locked loop (PLL) is achieved by utilizing an even-harmonics-nulled series-coupled quadrature oscillator (QVCO) and an in-band noise-aware charge pump (CP) design. The transceiver achieves a measured data rate of 0.8 Gbps with power consumption of 16 mW and 31.5 mW for the transmitter and the receiver, respectively. The optimized integrated phase noise of the PLL is 0.52° at 4.025 GHz. Project supported by the National Science and Technology Major Project of China (No. 2011ZX03004-002-01).

Grid Integration of Single Stage Solar PV System using Three-level Voltage Source Converter

NASA Astrophysics Data System (ADS)

Hussain, Ikhlaq; Kandpal, Maulik; Singh, Bhim

2016-08-01

This paper presents a single stage solar PV (photovoltaic) grid integrated power generating system using a three level voltage source converter (VSC) operating at low switching frequency of 900 Hz with robust synchronizing phase locked loop (RS-PLL) based control algorithm. To track the maximum power from solar PV array, an incremental conductance algorithm is used and this maximum power is fed to the grid via three-level VSC. The use of single stage system with three level VSC offers the advantage of low switching losses and the operation at high voltages and high power which results in enhancement of power quality in the proposed system. Simulated results validate the design and control algorithm under steady state and dynamic conditions.

Coordinated design of coding and modulation systems

NASA Technical Reports Server (NTRS)

Massey, J. L.

1976-01-01

Work on partial unit memory codes continued; it was shown that for a given virtual state complexity, the maximum free distance over the class of all convolutional codes is achieved within the class of unit memory codes. The effect of phase-lock loop (PLL) tracking error on coding system performance was studied by using the channel cut-off rate as the measure of quality of a modulation system. Optimum modulation signal sets for a non-white Gaussian channel considered an heuristic selection rule based on a water-filling argument. The use of error correcting codes to perform data compression by the technique of syndrome source coding was researched and a weight-and-error-locations scheme was developed that is closely related to LDSC coding.

Stepwise Loop Insertion Strategy for Active Site Remodeling to Generate Novel Enzyme Functions.

PubMed

Hoque, Md Anarul; Zhang, Yong; Chen, Liuqing; Yang, Guangyu; Khatun, Mst Afroza; Chen, Haifeng; Hao, Liu; Feng, Yan

2017-05-19

The remodeling of active sites to generate novel biocatalysts is an attractive and challenging task. We developed a stepwise loop insertion strategy (StLois), in which randomized residue pairs are inserted into active site loops. The phosphotriesterase-like lactonase from Geobacillus kaustophilus (GkaP-PLL) was used to investigate StLois's potential for changing enzyme function. By inserting six residues into active site loop 7, the best variant ML7-B6 demonstrated a 16-fold further increase in catalytic efficiency toward ethyl-paraoxon compared with its initial template, that is a 609-fold higher, >10 7 fold substrate specificity shift relative to that of wild-type lactonase. The remodeled variants displayed 760-fold greater organophosphate hydrolysis activity toward the organophosphates parathion, diazinon, and chlorpyrifos. Structure and docking computations support the source of notably inverted enzyme specificity. Considering the fundamental importance of active site loops, the strategy has potential for the rapid generation of novel enzyme functions by loop remodeling.

Clock recovery PLL with gated PFD for NRZ ON-OFF Modulated Signals in a retinal implant system.

PubMed

Brendler, Christian; Aryan, Naser Pour; Rieger, Viola; Rothermel, Albrecht

2013-01-01

A Clock Recovery Phase Locked Loop with Gated Phase Frequency Detector (GPLL) for NRZ ON-OFF Modulated Signals with low data transmission rates for an inductively powered subretinal implant system is presented. Low data transmission rate leads to a long absence of inductive powering in the system when zeros are transmitted. Consequently there is no possibility to extract any clock in these pauses, thus the digital circuitry can not work any more. Compared to a commonly used PLL for clock extraction, no certain amount of data transitions is needed. This is achieved by having two operating modes. In one mode the GPLL tracks the HF input signal. In the other, the GPLL is an adjustable oscillator oscillating at the last used frequency. The proposed GPLL is fabricated and measured using a 350 nm High Voltage CMOS technology.

Design and Verification of a Digital Controller for a 2-Piece Hemispherical Resonator Gyroscope.

PubMed

Lee, Jungshin; Yun, Sung Wook; Rhim, Jaewook

2016-04-20

A Hemispherical Resonator Gyro (HRG) is the Coriolis Vibratory Gyro (CVG) that measures rotation angle or angular velocity using Coriolis force acting the vibrating mass. A HRG can be used as a rate gyro or integrating gyro without structural modification by simply changing the control scheme. In this paper, differential control algorithms are designed for a 2-piece HRG. To design a precision controller, the electromechanical modelling and signal processing must be pre-performed accurately. Therefore, the equations of motion for the HRG resonator with switched harmonic excitations are derived with the Duhamel Integral method. Electromechanical modeling of the resonator, electric module and charge amplifier is performed by considering the mode shape of a thin hemispherical shell. Further, signal processing and control algorithms are designed. The multi-flexing scheme of sensing, driving cycles and x, y-axis switching cycles is appropriate for high precision and low maneuverability systems. The differential control scheme is easily capable of rejecting the common mode errors of x, y-axis signals and changing the rate integrating mode on basis of these studies. In the rate gyro mode the controller is composed of Phase-Locked Loop (PLL), amplitude, quadrature and rate control loop. All controllers are designed on basis of a digital PI controller. The signal processing and control algorithms are verified through Matlab/Simulink simulations. Finally, a FPGA and DSP board with these algorithms is verified through experiments.

A reconfigurable cryogenic platform for the classical control of quantum processors

NASA Astrophysics Data System (ADS)

Homulle, Harald; Visser, Stefan; Patra, Bishnu; Ferrari, Giorgio; Prati, Enrico; Sebastiano, Fabio; Charbon, Edoardo

2017-04-01

The implementation of a classical control infrastructure for large-scale quantum computers is challenging due to the need for integration and processing time, which is constrained by coherence time. We propose a cryogenic reconfigurable platform as the heart of the control infrastructure implementing the digital error-correction control loop. The platform is implemented on a field-programmable gate array (FPGA) that supports the functionality required by several qubit technologies and that can operate close to the physical qubits over a temperature range from 4 K to 300 K. This work focuses on the extensive characterization of the electronic platform over this temperature range. All major FPGA building blocks (such as look-up tables (LUTs), carry chains (CARRY4), mixed-mode clock manager (MMCM), phase-locked loop (PLL), block random access memory, and IDELAY2 (programmable delay element)) operate correctly and the logic speed is very stable. The logic speed of LUTs and CARRY4 changes less then 5%, whereas the jitter of MMCM and PLL clock managers is reduced by 20%. The stability is finally demonstrated by operating an integrated 1.2 GSa/s analog-to-digital converter (ADC) with a relatively stable performance over temperature. The ADCs effective number of bits drops from 6 to 4.5 bits when operating at 15 K.

A reconfigurable cryogenic platform for the classical control of quantum processors.

PubMed

Homulle, Harald; Visser, Stefan; Patra, Bishnu; Ferrari, Giorgio; Prati, Enrico; Sebastiano, Fabio; Charbon, Edoardo

2017-04-01

The implementation of a classical control infrastructure for large-scale quantum computers is challenging due to the need for integration and processing time, which is constrained by coherence time. We propose a cryogenic reconfigurable platform as the heart of the control infrastructure implementing the digital error-correction control loop. The platform is implemented on a field-programmable gate array (FPGA) that supports the functionality required by several qubit technologies and that can operate close to the physical qubits over a temperature range from 4 K to 300 K. This work focuses on the extensive characterization of the electronic platform over this temperature range. All major FPGA building blocks (such as look-up tables (LUTs), carry chains (CARRY4), mixed-mode clock manager (MMCM), phase-locked loop (PLL), block random access memory, and IDELAY2 (programmable delay element)) operate correctly and the logic speed is very stable. The logic speed of LUTs and CARRY4 changes less then 5%, whereas the jitter of MMCM and PLL clock managers is reduced by 20%. The stability is finally demonstrated by operating an integrated 1.2 GSa/s analog-to-digital converter (ADC) with a relatively stable performance over temperature. The ADCs effective number of bits drops from 6 to 4.5 bits when operating at 15 K.

Design, synthesis, and evaluation of VEGFR-targeted macromolecular MRI contrast agent based on biotin-avidin-specific binding.

PubMed

Liu, Yongjun; Wu, Xiaoyun; Sun, Xiaohe; Wang, Dan; Zhong, Ying; Jiang, Dandan; Wang, Tianqi; Yu, Dexin; Zhang, Na

2017-01-01

Developing magnetic resonance imaging (MRI) contrast agents with high relaxivity and specificity was essential to increase MRI diagnostic sensitivity and accuracy. In this study, the MRI contrast agent, vascular endothelial growth factor receptor (VEGFR)-targeted poly (l-lysine) (PLL)-diethylene triamine pentacetate acid (DTPA)-gadolinium (Gd) (VEGFR-targeted PLL-DTPA-Gd, VPDG), was designed and prepared to enhance the MRI diagnosis capacity of tumor. Biotin-PLL-DTPA-Gd was synthesized first, then, VEGFR antibody was linked to biotin-PLL-DTPA-Gd using biotin-avidin reaction. In vitro cytotoxicity study results showed that VPDG had low toxicity to MCF-7 cells and HepG2 cells at experimental concentrations. In cell uptake experiments, VPDG could significantly increase the internalization rates (61.75%±5.22%) in VEGFR-positive HepG2 cells compared to PLL-DTPA-Gd (PDG) (25.16%±4.71%, P <0.05). In MRI studies in vitro, significantly higher T1 relaxivity (14.184 mM -1 s -1 ) was observed compared to Magnevist ® (4.9 mM -1 s -1 ; P <0.01). Furthermore, in vivo MRI study results showed that VPDG could significantly enhance the tumor signal intensity and prolong the diagnostic time (from <1 h to 2.5 h). These results indicated that macromolecular VPDG was a promising MRI contrast agent and held great potential for molecular diagnosis of tumor.

Design, synthesis, and evaluation of VEGFR-targeted macromolecular MRI contrast agent based on biotin–avidin-specific binding

PubMed Central

Liu, Yongjun; Wu, Xiaoyun; Sun, Xiaohe; Wang, Dan; Zhong, Ying; Jiang, Dandan; Wang, Tianqi; Yu, Dexin; Zhang, Na

2017-01-01

Developing magnetic resonance imaging (MRI) contrast agents with high relaxivity and specificity was essential to increase MRI diagnostic sensitivity and accuracy. In this study, the MRI contrast agent, vascular endothelial growth factor receptor (VEGFR)-targeted poly (l-lysine) (PLL)-diethylene triamine pentacetate acid (DTPA)-gadolinium (Gd) (VEGFR-targeted PLL-DTPA-Gd, VPDG), was designed and prepared to enhance the MRI diagnosis capacity of tumor. Biotin-PLL-DTPA-Gd was synthesized first, then, VEGFR antibody was linked to biotin-PLL-DTPA-Gd using biotin–avidin reaction. In vitro cytotoxicity study results showed that VPDG had low toxicity to MCF-7 cells and HepG2 cells at experimental concentrations. In cell uptake experiments, VPDG could significantly increase the internalization rates (61.75%±5.22%) in VEGFR-positive HepG2 cells compared to PLL-DTPA-Gd (PDG) (25.16%±4.71%, P<0.05). In MRI studies in vitro, significantly higher T1 relaxivity (14.184 mM−1 s−1) was observed compared to Magnevist® (4.9 mM−1 s−1; P<0.01). Furthermore, in vivo MRI study results showed that VPDG could significantly enhance the tumor signal intensity and prolong the diagnostic time (from <1 h to 2.5 h). These results indicated that macromolecular VPDG was a promising MRI contrast agent and held great potential for molecular diagnosis of tumor. PMID:28765707

All-Digital Baseband 65nm PLL/FPLL Clock Multiplier using 10-cell Library

NASA Technical Reports Server (NTRS)

Shuler, Robert L., Jr.; Wu, Qiong; Liu, Rui; Chen, Li

2014-01-01

PLLs for clock generation are essential for modern circuits, to generate specialized frequencies for many interfaces and high frequencies for chip internal operation. These circuits depend on analog circuits and careful tailoring for each new process, and making them fault tolerant is an incompletely solved problem. Until now, all digital PLLs have been restricted to sampled data DSP techniques and not available for the highest frequency baseband applications. This paper presents the design and preliminary evaluation of an all-digital baseband technique built entirely with an easily portable 10-cell digital library. The library is also described, as it aids in research and low volume design porting to new processes. The advantages of the digital approach are the wide variety of techniques available to give varying degrees of fault tolerance, and the simplicity of porting the design to new processes, even to exotic processes that may not have analog capability. The only tuning parameter is digital gate delay. An all-digital approach presents unique problems and standard analog loop stability design criteria cannot be directly used. Because of the quantization of frequency, there is effectively infinite gain for very small loop error feedback. The numerically controlled oscillator (NCO) based on a tapped delay line cannot be reliably updated while a pulse is active in the delay line, and ordinarily does not have enough frequency resolution for a low-jitter output.

ALL-Digital Baseband 65nm PLL/FPLL Clock Multiplier Using 10-Cell Library

NASA Technical Reports Server (NTRS)

Schuler, Robert L., Jr.; Wu, Qiong; Liu, Rui; Chen, Li; Madala, Shridhar

2014-01-01

PLLs for clock generation are essential for modern circuits, to generate specialized frequencies for many interfaces and high frequencies for chip internal operation. These circuits depend on analog circuits and careful tailoring for each new process, and making them fault tolerant is an incompletely solved problem. Until now, all digital PLLs have been restricted to sampled data DSP techniques and not available for the highest frequency baseband applications. This paper presents the design and preliminary evaluation of an all-digital baseband technique built entirely with an easily portable 10-cell digital library. The library is also described, as it aids in research and low volume design porting to new processes. The advantages of the digital approach are the wide variety of techniques available to give varying degrees of fault tolerance, and the simplicity of porting the design to new processes, even to exotic processes that may not have analog capability. The only tuning parameter is digital gate delay. An all-digital approach presents unique problems and standard analog loop stability design criteria cannot be directly used. Because of the quantization of frequency, there is effectively infinite gain for very small loop error feedback. The numerically controlled oscillator (NCO) based on a tapped delay line cannot be reliably updated while a pulse is active in the delay line, and ordinarily does not have enough frequency resolution for a low-jitter output.

A 2.4-GHz Energy-Efficient Transmitter for Wireless Medical Applications.

PubMed

Qi Zhang; Peng Feng; Zhiqing Geng; Xiaozhou Yan; Nanjian Wu

2011-02-01

A 2.4-GHz energy-efficient transmitter (TX) for wireless medical applications is presented in this paper. It consists of four blocks: a phase-locked loop (PLL) synthesizer with a direct frequency presetting technique, a class-B power amplifier, a digital processor, and nonvolatile memory (NVM). The frequency presetting technique can accurately preset the carrier frequency of the voltage-controlled oscillator and reduce the lock-in time of the PLL synthesizer, further increasing the data rate of communication with low power consumption. The digital processor automatically compensates preset frequency variation with process, voltage, and temperature. The NVM stores the presetting signals and calibration data so that the TX can avoid the repetitive calibration process and save the energy in practical applications. The design is implemented in 0.18- μm radio-frequency complementary metal-oxide semiconductor process and the active area is 1.3 mm (2). The TX achieves 0-dBm output power with a maximum data rate of 4 Mb/s/2 Mb/s and dissipates 2.7-mA/5.4-mA current from a 1.8-V power supply for on-off keying/frequency-shift keying modulation, respectively. The corresponding energy efficiency is 1.2 nJ/b·mW and 4.8 nJ/b· mW when normalized to the transmitting power.

VCO PLL Frequency Synthesizers for Spacecraft Transponders

NASA Technical Reports Server (NTRS)

Smith, Scott; Mysoor, Narayan; Lux, James; Cook, Brian

2007-01-01

Two documents discuss a breadboard version of advanced transponders that, when fully developed, would be installed on future spacecraft to fly in deep space. These transponders will be required to be capable of operation on any deepspace- communications uplink frequency channel between 7,145 and 7,235 MHz, and any downlink frequency channel between 8,400 and 8,500 MHz. The document focuses on the design and operation of frequency synthesizers for the receiver and transmitter. Heretofore, frequency synthesizers in deep-space transponders have been based on dielectric resonator oscillators (DROs), which do not have the wide tuning bandwidth necessary to tune over all channels in the uplink or downlink frequency bands. To satisfy the requirement for tuning bandwidth, the present frequency synthesizers are based on voltage-controlled-oscillator (VCO) phase-locked loops (PLLs) implemented by use of monolithic microwave integrated circuits (MMICs) implemented using inGaP heterojunction bipolar transistor (HBT) technology. MMIC VCO PLL frequency synthesizers similar to the present ones have been used in commercial and military applications but, until now, have exhibited too much phase noise for use in deep-space transponders. The present frequency synthesizers contain advanced MMIC VCOs, which use HBT technology and have lower levels of flicker (1/f) phase noise. When these MMIC VCOs are used with high-speed MMIC frequency dividers, it becomes possible to obtain the required combination of frequency agility and low phase noise.

Single-chip fully integrated direct-modulation CMOS RF transmitters for short-range wireless applications.

PubMed

El-Desouki, Munir M; Qasim, Syed Manzoor; BenSaleh, Mohammed; Deen, M Jamal

2013-08-02

Ultra-low power radio frequency (RF) transceivers used in short-range application such as wireless sensor networks (WSNs) require efficient, reliable and fully integrated transmitter architectures with minimal building blocks. This paper presents the design, implementation and performance evaluation of single-chip, fully integrated 2.4 GHz and 433 MHz RF transmitters using direct-modulation power voltage-controlled oscillators (PVCOs) in addition to a 2.0 GHz phase-locked loop (PLL) based transmitter. All three RF transmitters have been fabricated in a standard mixed-signal CMOS 0.18 µm technology. Measurement results of the 2.4 GHz transmitter show an improvement in drain efficiency from 27% to 36%. The 2.4 GHz and 433 MHz transmitters deliver an output power of 8 dBm with a phase noise of -122 dBc/Hz at 1 MHz offset, while drawing 15.4 mA of current and an output power of 6.5 dBm with a phase noise of -120 dBc/Hz at 1 MHz offset, while drawing 20.8 mA of current from 1.5 V power supplies, respectively. The PLL transmitter delivers an output power of 9 mW with a locking range of 128 MHz and consumes 26 mA from 1.8 V power supply. The experimental results demonstrate that the RF transmitters can be efficiently used in low power WSN applications.

An Autonomous Satellite Time Synchronization System Using Remotely Disciplined VC-OCXOs.

PubMed

Gu, Xiaobo; Chang, Qing; Glennon, Eamonn P; Xu, Baoda; Dempseter, Andrew G; Wang, Dun; Wu, Jiapeng

2015-07-23

An autonomous remote clock control system is proposed to provide time synchronization and frequency syntonization for satellite to satellite or ground to satellite time transfer, with the system comprising on-board voltage controlled oven controlled crystal oscillators (VC-OCXOs) that are disciplined to a remote master atomic clock or oscillator. The synchronization loop aims to provide autonomous operation over extended periods, be widely applicable to a variety of scenarios and robust. A new architecture comprising the use of frequency division duplex (FDD), synchronous time division (STDD) duplex and code division multiple access (CDMA) with a centralized topology is employed. This new design utilizes dual one-way ranging methods to precisely measure the clock error, adopts least square (LS) methods to predict the clock error and employs a third-order phase lock loop (PLL) to generate the voltage control signal. A general functional model for this system is proposed and the error sources and delays that affect the time synchronization are discussed. Related algorithms for estimating and correcting these errors are also proposed. The performance of the proposed system is simulated and guidance for selecting the clock is provided.

A recursive solution for a fading memory filter derived from Kalman filter theory

NASA Technical Reports Server (NTRS)

Statman, J. I.

1986-01-01

A simple recursive solution for a class of fading memory tracking filters is presented. A fading memory filter provides estimates of filter states based on past measurements, similar to a traditional Kalman filter. Unlike a Kalman filter, an exponentially decaying weight is applied to older measurements, discounting their effect on present state estimates. It is shown that Kalman filters and fading memory filters are closely related solutions to a general least squares estimator problem. Closed form filter transfer functions are derived for a time invariant, steady state, fading memory filter. These can be applied in loop filter implementation of the Deep Space Network (DSN) Advanced Receiver carrier phase locked loop (PLL).

Molecular dynamics simulation of coarse-grained poly(L-lysine) dendrimers.

PubMed

Rahimi, Ali; Amjad-Iranagh, Sepideh; Modarress, Hamid

2016-03-01

Poly(L-lysine) (PLL) dendrimer are amino acid based macromolecules and can be used as drug delivery agents. Their branched structure allows them to be functionalized by various groups to encapsulate drug agents into their structure. In this work, at first, an attempt was made on all-atom simulation of PLL dendrimer of different generations. Based on all-atom results, a course-grained model of this dendrimer was designed and its parameters were determined, to be used for simulation of three generations of PLL dendrimer, at two pHs. Similar to the all-atom, the coarse-grained results indicated that by increasing the generation, the dendrimer becomes more spherical. At pH 7, the dendrimer had larger size, whereas at pH 12, due to back folding of branching chains, they had the tendency to penetrate into the inner layers. The calculated radial probability and radial distribution functions confirm that at pH 7, the PLL dendrimer has more cavities and as a result it can encapsulate more water molecules into its inner structure. By calculating the moment of inertia and the aspect ratio, the formation of spherical structure for PLL dendrimer was confirmed.

Design and Verification of a Digital Controller for a 2-Piece Hemispherical Resonator Gyroscope

PubMed Central

Lee, Jungshin; Yun, Sung Wook; Rhim, Jaewook

2016-01-01

A Hemispherical Resonator Gyro (HRG) is the Coriolis Vibratory Gyro (CVG) that measures rotation angle or angular velocity using Coriolis force acting the vibrating mass. A HRG can be used as a rate gyro or integrating gyro without structural modification by simply changing the control scheme. In this paper, differential control algorithms are designed for a 2-piece HRG. To design a precision controller, the electromechanical modelling and signal processing must be pre-performed accurately. Therefore, the equations of motion for the HRG resonator with switched harmonic excitations are derived with the Duhamel Integral method. Electromechanical modeling of the resonator, electric module and charge amplifier is performed by considering the mode shape of a thin hemispherical shell. Further, signal processing and control algorithms are designed. The multi-flexing scheme of sensing, driving cycles and x, y-axis switching cycles is appropriate for high precision and low maneuverability systems. The differential control scheme is easily capable of rejecting the common mode errors of x, y-axis signals and changing the rate integrating mode on basis of these studies. In the rate gyro mode the controller is composed of Phase-Locked Loop (PLL), amplitude, quadrature and rate control loop. All controllers are designed on basis of a digital PI controller. The signal processing and control algorithms are verified through Matlab/Simulink simulations. Finally, a FPGA and DSP board with these algorithms is verified through experiments. PMID:27104539

The Ionospheric Scintillation Effects on the BeiDou Signal Receiver

PubMed Central

He, Zhijun; Zhao, Hongbo; Feng, Wenquan

2016-01-01

Irregularities in the Earth’s ionosphere can make the amplitude and phase of radio signals fluctuate rapidly, which is known as ionospheric scintillation. Severe ionospheric scintillation could affect the performance of the Global Navigation Satellite System (GNSS). Currently, the Multiple Phase Screen (MPS) technique is widely used in solving problems caused by weak and strong scintillations. Considering that Southern China is mainly located in the area where moderate and intense scintillation occur frequently, this paper built a model based on the MPS technique and discussed the scintillation impacts on China’s BeiDou navigation system. By using the BeiDou B1I signal, this paper analyzed the scintillation effects on the receiver, which includes the acquisition and tracking process. For acquisition process, this paper focused on the correlation peak and acquisition probability. For the tracking process, this paper focused on the carrier tracking loop and the code tracking loop. Simulation results show that under high scintillation intensity, the phase fluctuation could be −1.13 ± 0.087 rad to 1.40 ± 0.087 rad and the relative amplitude fluctuation could be −10 dB to 8 dB. As the scintillation intensity increased, the average correlation peak would decrease more than 8%, which could thus degrade acquisition performance. On the other hand, when the signal-to-noise ratio (SNR) is comparatively lower, the influence of strong scintillation on the phase locked loop (PLL) is much higher than that of weak scintillation. As the scintillation becomes more intense, PLL variance could consequently results in an error of more than 2.02 cm in carrier-phase based ranging. In addition, the delay locked loop (DLL) simulation results indicated that the pseudo-range error caused by strong scintillation could be more than 4 m and the consequent impact on positioning accuracy could be more than 6 m. PMID:27834867

NASA GSFC Report on CCSDS Recommendations 2.1.8A B Minimum Earth Station Transmitter Frequency Resolution for Spacecraft Receiver Acquisition

NASA Technical Reports Server (NTRS)

Fong, Wai; Lee, Wing

2017-01-01

In Fall 2016, ESA presented paper SLS-RFM 16-10 documenting a possible issue with the frequency lock-in range specification in Recommendation 2.1.8A of typically 267 to 1067 Hz in considerings (b) from considerings (a) for loop bandwidths [2B(sub LO)] in the range of 200 to 800 Hz with a recommendation of 100 Hz step size for frequency sweeping. The paper calculated the lock-in range to be (+/-)266 to (+/-)1064 rad/s or (+/-)42 to (+/-)168 Hz. Also, Recommendation 2.1.8B has the same issue for considering (a) and (b), i.e. for 2B(sub LO) =10 Hz, a lock-in range of 13 Hz was specified and a recommendation of 5 Hz step size for frequency sweeping. ESA also provided test results from the Rosetta and Exomars transponders. The results were somewhat inconsistent since the tests to verify lock-in and pull-in range did not include acquisition time, which is vital to the definition of these performance measures. This paper will address these test results below. However, we first examine the rationale for Recommendation 2.1.8A/B and its consistency with the theory of 2nd order phase lock loop operations. Our approach is to design a digital phase locked loop (DPLL) from phase locked loop (PLL) requirements. All analysis will be performed with a DPLL.

Enhanced cell uptake via non-covalent decollation of a single-walled carbon nanotube-DNA hybrid with polyethylene glycol-grafted poly(l-lysine) labeled with an Alexa-dye and its efficient uptake in a cancer cell

NASA Astrophysics Data System (ADS)

Fujigaya, Tsuyohiko; Yamamoto, Yuki; Kano, Arihiro; Maruyama, Atsushi; Nakashima, Naotoshi

2011-10-01

The use of single-walled carbon nanotubes (SWNTs) for biomedical applications is a promising approach due to their unique outer optical stimuli response properties, such as a photothermal response triggered by near-IR laser irradiation. The challenging task in order to realize such applications is to render the SWNTs biocompatible. For this purpose, the stable and homogeneous functionalization of the SWNTs with a molecule carrying a biocompatible group is very important. Here, we describe the design and synthesis of a polyanionic SWNT/DNA hybrid combined with a cationic poly(l-lysine) grafted by polyethylene glycol (PLL-g-PEG) to provide a supramolecular SWNT assembly. A titration experiment revealed that the assembly undergoes an approximately 1 : 1 reaction of the SWNT/DNA with PLL-g-PEG. We also found that SWNT/DNA is coated with PLL-g-PEG very homogeneously that avoids the non-specific binding of proteins on the SWNT surface. The experiment using the obtained supramolecular hybrid was carried out in vitro and a dramatic enhancement in the cell uptake efficiency compared to that of the SWNT/DNA hybrid without PLL-g-PEG was found.The use of single-walled carbon nanotubes (SWNTs) for biomedical applications is a promising approach due to their unique outer optical stimuli response properties, such as a photothermal response triggered by near-IR laser irradiation. The challenging task in order to realize such applications is to render the SWNTs biocompatible. For this purpose, the stable and homogeneous functionalization of the SWNTs with a molecule carrying a biocompatible group is very important. Here, we describe the design and synthesis of a polyanionic SWNT/DNA hybrid combined with a cationic poly(l-lysine) grafted by polyethylene glycol (PLL-g-PEG) to provide a supramolecular SWNT assembly. A titration experiment revealed that the assembly undergoes an approximately 1 : 1 reaction of the SWNT/DNA with PLL-g-PEG. We also found that SWNT/DNA is coated with PLL-g-PEG very homogeneously that avoids the non-specific binding of proteins on the SWNT surface. The experiment using the obtained supramolecular hybrid was carried out in vitro and a dramatic enhancement in the cell uptake efficiency compared to that of the SWNT/DNA hybrid without PLL-g-PEG was found. Electronic supplementary information (ESI) available: Additional absorption spectra, DLS plots and PL spectra. See DOI: 10.1039/c1nr10635j

Pixel parallel localized driver design for a 128 x 256 pixel array 3D 1Gfps image sensor

NASA Astrophysics Data System (ADS)

Zhang, C.; Dao, V. T. S.; Etoh, T. G.; Charbon, E.

2017-02-01

In this paper, a 3D 1Gfps BSI image sensor is proposed, where 128 × 256 pixels are located in the top-tier chip and a 32 × 32 localized driver array in the bottom-tier chip. Pixels are designed with Multiple Collection Gates (MCG), which collects photons selectively with different collection gates being active at intervals of 1ns to achieve 1Gfps. For the drivers, a global PLL is designed, which consists of a ring oscillator with 6-stage current starved differential inverters, achieving a wide frequency tuning range from 40MHz to 360MHz (20ps rms jitter). The drivers are the replicas of the ring oscillator that operates within a PLL. Together with level shifters and XNOR gates, continuous 3.3V pulses are generated with desired pulse width, which is 1/12 of the PLL clock period. The driver array is activated by a START signal, which propagates through a highly balanced clock tree, to activate all the pixels at the same time with virtually negligible skew.

Frequency-Tracking CW Doppler Radar Solving Small-Angle Approximation and Null Point Issues in Non-Contact Vital Signs Monitoring.

PubMed

Mercuri, Marco; Liu, Yao-Hong; Lorato, Ilde; Torfs, Tom; Bourdoux, Andre; Van Hoof, Chris

2017-06-01

A Doppler radar operating as a Phase-Locked-Loop (PLL) in frequency demodulator configuration is presented and discussed. The proposed radar presents a unique architecture, using a single channel mixer, and allows to detect contactless vital signs parameters while solving the null point issue and without requiring the small angle approximation condition. Spectral analysis, simulations, and experimental results are presented and detailed to demonstrate the feasibility and the operational principle of the proposed radar architecture.

Radiation Tolerant, Low Noise Phase Locked Loops in 65 nm CMOS Technology

NASA Astrophysics Data System (ADS)

Prinzie, Jeffrey; Christiansen, Jorgen; Moreira, Paulo; Steyaert, Michiel; Leroux, Paul

2018-04-01

This work presents an introduction to radiation hardened Phase Locked Loops (PLLs) for nuclear and high-energy physics application. An experimental circuit has been fabricated and irradiated with Xrays up to 600 Mrad. Heavy ions with an LET between 3.2 and 69.2 MeV.cm2/mg were used to verify the SEU cross section of the devices. A Two-photon Absorption (TPA) laser facility has been used to provide detailed results on the SEU sensitivity. The presented circuit employs TMR in the digital logic and an asynchronous phase-frequency detector (PFD) is presented. The PLL has a ringand LC-oscillator to be compared experimentally. The circuit has been fabricated in a 65 nm CMOS technology.

Asymmetric resonance response analysis of a thermally excited silicon microcantilever for mass-sensitive nanoparticle detection

NASA Astrophysics Data System (ADS)

Bertke, Maik; Hamdana, Gerry; Wu, Wenze; Wasisto, Hutomo Suryo; Peiner, Erwin

2017-06-01

The asymmetric resonance responses of a thermally actuated silicon microcantilever of a portable, cantilever-based nanoparticle detector (Cantor) is analysed. For airborne nanoparticle concentration measurements, the cantilever is excited in its first in-plane bending mode by an integrated p-type heating actuator. The mass-sensitive nanoparticle (NP) detection is based on the resonance frequency (f0) shifting due to the deposition of NPs. A homemade phase-locked loop (PLL) circuit is developed for tracking of f0. For deflection sensing the cantilever contains an integrated piezo-resistive Wheatstone bridge (WB). A new fitting function based on the Fano resonance is proposed for analysing the asymmetric resonance curves including a method for calculating the quality factor Q from the fitting parameters. To obtain a better understanding, we introduce an electrical equivalent circuit diagram (ECD) comprising a series resonant circuit (SRC) for the cantilever resonator and voltage sources for the parasitics, which enables us to simulate the asymmetric resonance response and discuss the possible causes. Furthermore, we compare the frequency response of the on-chip thermal excitation with an external excitation using an in-plane piezo actuator revealing parasitic heating of the WB as the origin of the asymmetry. Moreover, we are able to model the phase component of the sensor output using the ECD. Knowing and understanding the phase response is crucial to the design of the PLL and thus the next generation of Cantor.

An Autonomous Satellite Time Synchronization System Using Remotely Disciplined VC-OCXOs

PubMed Central

Gu, Xiaobo; Chang, Qing; Glennon, Eamonn P.; Xu, Baoda; Dempseter, Andrew G.; Wang, Dun; Wu, Jiapeng

2015-01-01

An autonomous remote clock control system is proposed to provide time synchronization and frequency syntonization for satellite to satellite or ground to satellite time transfer, with the system comprising on-board voltage controlled oven controlled crystal oscillators (VC-OCXOs) that are disciplined to a remote master atomic clock or oscillator. The synchronization loop aims to provide autonomous operation over extended periods, be widely applicable to a variety of scenarios and robust. A new architecture comprising the use of frequency division duplex (FDD), synchronous time division (STDD) duplex and code division multiple access (CDMA) with a centralized topology is employed. This new design utilizes dual one-way ranging methods to precisely measure the clock error, adopts least square (LS) methods to predict the clock error and employs a third-order phase lock loop (PLL) to generate the voltage control signal. A general functional model for this system is proposed and the error sources and delays that affect the time synchronization are discussed. Related algorithms for estimating and correcting these errors are also proposed. The performance of the proposed system is simulated and guidance for selecting the clock is provided. PMID:26213929

Drastic stabilization of parallel DNA hybridizations by a polylysine comb-type copolymer with hydrophilic graft chain.

PubMed

Miyoshi, Daisuke; Ueda, Yu-Mi; Shimada, Naohiko; Nakano, Shu-Ichi; Sugimoto, Naoki; Maruyama, Atsushi

2014-09-01

Electrostatic interactions play a major role in protein-DNA interactions. As a model system of a cationic protein, herein we focused on a comb-type copolymer of a polycation backbone and dextran side chains, poly(L-lysine)-graft-dextran (PLL-g-Dex), which has been reported to form soluble interpolyelectrolyte complexes with DNA strands. We investigated the effects of PLL-g-Dex on the conformation and thermodynamics of DNA oligonucleotides forming various secondary structures. Thermodynamic analysis of the DNA structures showed that the parallel conformations involved in both DNA duplexes and triplexes were significantly and specifically stabilized by PLL-g-Dex. On the basis of thermodynamic parameters, it was further possible to design DNA switches that undergo structural transition responding to PLL-g-Dex from an antiparallel duplex to a parallel triplex even with mismatches in the third strand hybridization. These results suggest that polycationic molecules are able to induce structural polymorphism of DNA oligonucleotides, because of the conformation-selective stabilization effects. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Experimental Evaluation of an Invasive Medical Instrument Based on a Displacement Measurement System.

PubMed

Fotiadis, Dimitris A; Astaras, Alexandros; Bamidis, Panagiotis D; Papathanasiou, Kostas; Kalfas, Anestis

2015-09-01

This paper presents a novel method for tracking the position of a medical instrument's tip. The system is based on phase locking a high frequency signal transmitted from the medical instrument's tip to a reference signal. Displacement measurement is established having the loop open, in order to get a low frequency voltage representing the medical instrument's movement; therefore, positioning is established by means of conventional measuring techniques. The voltage-controlled oscillator stage of the phase-locked loop (PLL), combined to an appropriate antenna, comprises the associated transmitter located inside the medical instrument tip. All the other low frequency PLL components, low noise amplifier and mixer, are located outside the human body, forming the receiver part of the system. The operating details of the proposed system were coded in Verilog-AMS. Simulation results indicate robust medical instrument tracking in 1-D. Experimental evaluation of the proposed position tracking system is also presented. The experiments described in this paper are based on a transmitter moving opposite a stationary receiver performing either constant velocity or uniformly accelerated movement, and also together with two stationary receivers performing constant velocity movement again. This latter setup is implemented in order to demonstrate the prototype's accuracy for planar (2-D) motion measurements. Error analysis and time-domain analysis are presented for system performance characterization. Furthermore, preliminary experimental assessment using a saline solution container to more closely approximate the human body as a radio frequency wave transmission medium has proved the system's capability of operating underneath the skin.

Design of an Embedded CMOS Temperature Sensor for Passive RFID Tag Chips.

PubMed

Deng, Fangming; He, Yigang; Li, Bing; Zhang, Lihua; Wu, Xiang; Fu, Zhihui; Zuo, Lei

2015-05-18

This paper presents an ultra-low embedded power temperature sensor for passive RFID tags. The temperature sensor converts the temperature variation to a PTAT current, which is then transformed into a temperature-controlled frequency. A phase locked loop (PLL)-based sensor interface is employed to directly convert this temperature-controlled frequency into a corresponding digital output without an external reference clock. The fabricated sensor occupies an area of 0.021 mm2 using the TSMC 0.18 1P6M mixed-signal CMOS process. Measurement results of the embedded sensor within the tag system shows a 92 nW power dissipation under 1.0 V supply voltage at room temperature, with a sensing resolution of 0.15 °C/LSB and a sensing accuracy of -0.7/0.6 °C from -30 °C to 70 °C after 1-point calibration at 30 °C.

Design of an Embedded CMOS Temperature Sensor for Passive RFID Tag Chips

PubMed Central

Deng, Fangming; He, Yigang; Li, Bing; Zhang, Lihua; Wu, Xiang; Fu, Zhihui; Zuo, Lei

2015-01-01

This paper presents an ultra-low embedded power temperature sensor for passive RFID tags. The temperature sensor converts the temperature variation to a PTAT current, which is then transformed into a temperature-controlled frequency. A phase locked loop (PLL)-based sensor interface is employed to directly convert this temperature-controlled frequency into a corresponding digital output without an external reference clock. The fabricated sensor occupies an area of 0.021 mm2 using the TSMC 0.18 1P6M mixed-signal CMOS process. Measurement results of the embedded sensor within the tag system shows a 92 nW power dissipation under 1.0 V supply voltage at room temperature, with a sensing resolution of 0.15 °C/LSB and a sensing accuracy of −0.7/0.6 °C from −30 °C to 70 °C after 1-point calibration at 30 °C. PMID:25993518

A 0.8-4.2 GHz monolithic all-digital PLL based frequency synthesizer for wireless communications

NASA Astrophysics Data System (ADS)

Yuanxin, Zhao; Yuanpei, Gao; Wei, Li; Ning, Li; Junyan, Ren

2015-01-01

A 0.8-4.2 GHz monolithic all-digital PLL based frequency synthesizer for wireless communications is successfully realized by the 130 nm CMOS process. A series of novel methods are proposed in this paper. Two band DCOs with high frequency resolution are utilized to cover the frequency band of interest, which is as wide as 2.5 to 5 GHz. An overflow counter is proposed to prevent the “pulse-swallowing” phenomenon so as to significantly reduce the locking time. A NTW-clamp digital module is also proposed to prevent the overflow of the loop control word. A modified programmable divider is presented to prevent the failure operation at the boundary. The measurement results show that the output frequency range of this frequency synthesizer is 0.8-4.2 GHz. The locking time achieves a reduction of 84% at 2.68 GHz. The best in-band and out-band phase noise performances have reached -100 dBc/Hz, and -125 dBc/Hz respectively. The lowest reference spur is -58 dBc.

Specific immune response genes of the guinea pig. II. Relationship between the poly-L-lysine gene and the genes controlling immune responsiveness to copolymers of L-glutamic acid and L-alanine and L-glutamic acid and L-tyrosine in random-bred Hartley guinea pigs.

PubMed

Bluestein, H G; Green, I; Benacerraf, B

1971-08-01

The ability of guinea pigs to make immune responses to GA, a linear random copolymer of L-glutamic acid and L-alanine, GT, a random linear copolymer of L-glutamic acid and L-tyrosine, and PLL, a linear homopolymer of L-lysine, is controlled by different autosomal dominant genes specific for each of those polymers. We have investigated the relationship between the PLL gene and the GA and GT immune response genes by simultaneously immunizing random-bred Hartley strain guinea pigs with GA and PLL, GT and PLL, or GA and GT. In most Hartley guinea pigs the ability to respond immunologically to GA and to PLL is inherited together; that is, most animals responding to GA respond to PLL and vice versa. However, a few animals respond to either GA or to PLL but not both, demonstrating that the GA and PLL immune response genes are not identical but linked in most Hartley animals. Conversely, when simultaneously immunized with GT and PLL, most Hartley guinea pigs respond to either PLL or GT but not both, indicating that GT and PLL responsiveness tends to segregate away from each other. Thus, the GT and PLL immune response genes also are not inherited independently but, rather, behave as alleles or pseudoalleles. Similar results are observed when Hartley guinea pigs are simultaneously immunized with GA and GT. The ability to respond to GA segregates away from the ability to respond to GT. Our studies demonstrated that the specific immune response genes thus far identified in guinea pigs controlling the ability to respond to GA, GT, and PLL, respectively, are found on the same chromosome. In most Hartley animals, the GA and PLL immune response genes are often linked, i.e. occur on the same chromosome strand, and tend to behave as alleles or pseudoalleles to the GT immune response gene.

Quadrature demultiplexing using a degenerate vector parametric amplifier.

PubMed

Lorences-Riesgo, Abel; Liu, Lan; Olsson, Samuel L I; Malik, Rohit; Kumpera, Aleš; Lundström, Carl; Radic, Stojan; Karlsson, Magnus; Andrekson, Peter A

2014-12-01

We report on quadrature demultiplexing of a quadrature phase-shift keying (QPSK) signal into two cross-polarized binary phase-shift keying (BPSK) signals with negligible penalty at bit-error rate (BER) equal to 10(-9). The all-optical quadrature demultiplexing is achieved using a degenerate vector parametric amplifier operating in phase-insensitive mode. We also propose and demonstrate the use of a novel and simple phase-locked loop (PLL) scheme based on detecting the envelope of one of the signals after demultiplexing in order to achieve stable quadrature decomposition.

TGF-β1 related inflammation in the posterior longitudinal ligament of cervical spondylotic myelopathy patients.

PubMed

Wang, Jia-Zeng; Fang, Xiu-Tong; Lv, E; Yu, Fang; Wang, Zhen-Wei; Song, Hong-Xing

2015-01-01

This study aimed to elucidate the pathogenesis of posterior longitudinal ligament (PLL) hypertrophy. Cervical PLL specimens were collected from CSM patients during surgery (n = 30) and during routine autopsy (n = 14), and processed for histological examination (HE staining and Masson's Trichrome staining) and IHC (CD3, CD68, CD31, TGF-β1 and collagen II). In addition, the mRNA expression of collagen I was detected in cervical PLL specimens from 16 CSM patients (n = 16) and from routine autopsy (n = 16) by RT-PCR. Obvious fibrosis, cartilage metaplasia and calcification were found in the cervical PLL of CSM patients. In the degenerated PLL, CD68(+) macrophages were frequently identified, CD3(+) T lymphocytes were occasionally found, and many newly generated small vessels were also present. In the degenerated PLL, of the number of TGF-β1 positive cells increased markedly when compared with control group. IHC indicated TGF-β1 was secreted by macrophages. RT-PCR showed a significantly lower mRNA expression of collagen I in the PLL of CSM patients as compared to control group. Macrophages are the major type of inflammatory cells involved in the cervical PLL degeneration, and TGF-β1 is related to the cervical PLL degeneration. TGF-β1 is mainly secreted by macrophages. Anti-inflammation may serve as an alternative non-surgical treatment and prophylactic strategy for PLL degeneration.

Genome-wide characterization of the Pectate Lyase-like (PLL) genes in Brassica rapa.

PubMed

Jiang, Jingjing; Yao, Lina; Miao, Ying; Cao, Jiashu

2013-11-01

Pectate lyases (PL) depolymerize demethylated pectin (pectate, EC 4.2.2.2) by catalyzing the eliminative cleavage of α-1,4-glycosidic linked galacturonan. Pectate Lyase-like (PLL) genes are one of the largest and most complex families in plants. However, studies on the phylogeny, gene structure, and expression of PLL genes are limited. To understand the potential functions of PLL genes in plants, we characterized their intron-exon structure, phylogenetic relationships, and protein structures, and measured their expression patterns in various tissues, specifically the reproductive tissues in Brassica rapa. Sequence alignments revealed two characteristic motifs in PLL genes. The chromosome location analysis indicated that 18 of the 46 PLL genes were located in the least fractionated sub-genome (LF) of B. rapa, while 16 were located in the medium fractionated sub-genome (MF1) and 12 in the more fractionated sub-genome (MF2). Quantitative RT-PCR analysis showed that BrPLL genes were expressed in various tissues, with most of them being expressed in flowers. Detailed qRT-PCR analysis identified 11 pollen specific PLL genes and several other genes with unique spatial expression patterns. In addition, some duplicated genes showed similar expression patterns. The phylogenetic analysis identified three PLL gene subfamilies in plants, among which subfamily II might have evolved from gene neofunctionalization or subfunctionalization. Therefore, this study opens the possibility for exploring the roles of PLL genes during plant development.

Vortex spin-torque oscillator stabilized by phase locked loop using integrated circuits

NASA Astrophysics Data System (ADS)

Kreissig, Martin; Lebrun, R.; Protze, F.; Merazzo-Jaimes, K.; Hem, J.; Vila, L.; Ferreira, R.; Cyrille, M.-C.; Ellinger, F.; Cros, V.; Ebels, U.; Bortolotti, P.

2017-05-01

Spin-torque nano-oscillators (STO) are candidates for the next technological implementation of spintronic devices in commercial electronic systems. For use in microwave applications, improving the noise figures by efficient control of their phase dynamics is a mandatory requirement. In order to achieve this, we developed a compact phase locked loop (PLL) based on custom integrated circuits (ICs) and demonstrate that it represents an efficient way to reduce the phase noise level of a vortex based STO. The advantage of our approach to phase stabilize STOs is that our compact system is highly reconfigurable e.g. in terms of the frequency divider ratio N, RF gain and loop gain. This makes it robust against device to device variations and at the same time compatible with a large range of STOs. Moreover, by taking advantage of the natural highly non-isochronous nature of the STO, the STO frequency can be easily controlled by e.g. changing the divider ratio N.

miRNA oligonucleotide and sponge for miRNA-21 inhibition mediated by PEI-PLL in breast cancer therapy.

PubMed

Gao, Shiqian; Tian, Huayu; Guo, Ye; Li, Yuce; Guo, Zhaopei; Zhu, Xiaojuan; Chen, Xuesi

2015-10-01

MicroRNA-21 (miR-21) inhibition is a promising biological strategy for breast cancer therapy. However its application is limited by the lack of efficient miRNA inhibitor delivery systems. As a cationic polymer transfection material for nucleic acids, the poly (l-lysine)-modified polyethylenimine (PEI-PLL) copolymer combines the high transfection efficiency of polyethylenimine (PEI) and the good biodegradability of polyllysine (PLL). In this work, PEI-PLL was successfully synthesized and confirmed to transfect plasmid and oligonucleotide more effectively than PEI in MCF-7 cells (human breast cancer cells). In this regard, two kinds of miR-21 inhibitors, miR-21 sponge plasmid DNA (Sponge) and anti-miR-21 oligonucleotide (AMO), were transported into MCF-7 cells by PEI-PLL respectively. The miR-21 expression and the cellular physiology were determined post transfection. Compared with the negative control, PEI-PLL/Sponge or PEI-PLL/AMO groups exhibited lower miR-21 expression and cell viability. The anti-tumor mechanism of PEI-PLL/miR-21 inhibitors was further studied by cell cycle and western blot analyses. The results indicated that the miR-21 inhibition could induce the cell cycle arrest in G1 phase, upregulate the expression of Programmed Cell Death Protein 4 (PDCD4) and thus active the caspase-3 apoptosis pathway. Interestingly, the PEI-PLL/Sponge and PEI-PLL/AMO also sensitized the MCF-7 cells to anti-tumor drugs, doxorubicin (DOX) and cisplatin (CDDP). These results demonstrated that PEI-PLL/Sponge and PEI-PLL/AMO complexes would be two novel and promising gene delivery systems for breast cancer gene therapy based on miR-21 inhibition. This work was a combination of the high transfection efficiency of polyethylenimine (PEI), the good biodegradability of polyllysine (PLL) and the breast cancer-killing effect of miR-21 inhibitors. The poly (l-lysine)-modified polyethylenimine (PEI-PLL) copolymer was employed as the vector of miR-21 sponge plasmid DNA (Sponge) or anti-miR-21 oligonucleotide (AMO). PEI-PLL showed more transfection efficiency and lower cytotoxicity in human breast cancer cells than PEI. Moreover, the breast cancer cells exhibited significantly lower miR-21 expression and cell viability post transfection with sponge or AMO. Interestingly, the PEI-PLL/miR-21 inhibitor complexes also sensitized the cancer cells to anti-cancer chemotherapy drugs, doxorubicin (DOX) and cisplatin (CDDP). This synergistic effect provides a good application prospect of co-delivery miR-21 inhibitors and chemical drugs in breast cancer therapy. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Gold Nanoparticles Grafted with PLL-b-PNIPAM: Interplay on Thermal/pH Dual-Response and Optical Properties.

PubMed

Li, Hui-Juan; Li, Peng-Yun; Li, Li-Ying; Haleem, Abdul; He, Wei-Dong

2018-04-16

Narrowly distributed poly(l-lysine- b - N -isopropylacrylamide) (PLL- b -PNIPAM) was prepared through ring-opening polymerization of ε-benzyloxycarbonyl-l-lysine N -carboxy-α-amino anhydride and atom transfer radical polymerization of NIPAM, followed with the removal of ε-benzyloxycarbonyl group. Then gold nanoparticles (AuNPs) grafted with PLL- b -PNIPAM (PNIPAM-PLL-AuNPs) were obtained by the reduction of chloroauric acid with sodium citrate in the presence of PLL- b -PNIPAM. PNIPAM-PLL-AuNPs and its precursors were thoroughly characterized by proton magnetic resonance spectroscope, Fourier transform infrared spectroscope, UV-vis spectroscope, transmission electron microscopy, dynamic light scattering, thermogravimetric analysis, and circular dichroism. The obtained PNIPAM-PLL-AuNPs exhibited high colloid stability even at strong alkaline (pH = 12) and acidic (pH = 2) conditions. The thermal and pH dual-responsive behaviors of the grafting PLL- b -PNIPAM chains was observed to be affected by AuNPs, while not for the secondary structure of PLL chains. Correspondingly, the surface plasmon resonance (SPR) of AuNPs was found to be sensitive to both pH value and temperature. A blue shift in the SPR happened both with increasing pH value and increasing temperature. The stimuli-response was reversible in heating-cooling cycles. The gold nanoparticles with both pH and temperature response may have potential applications in biomedical areas and biosensors.

Interferon Inducers Against Infectious Diseases.

DTIC Science & Technology

1991-06-15

mouse there was little, if any, difference. b. PLL- Monosaccharide Grafts. The PLL-dextran grafts described above contain long polysaccharide chains...engrafted polysaccharides . Our research has resulted in the demonstration that effective IFN inducers can be formulated without using...Action of IC-(PLL-dextran) .............. 7. Induction of IFN in Mice by IC-(PLL- monosaccharides ). I 8. ICL-SCDS04; Compositions and IFN Titers

ToF-SIMS analysis of poly(L-lysine)-graft-poly(2-methyl-2-oxazoline) ultrathin adlayers.

PubMed

Pidhatika, Bidhari; Chen, Yin; Coullerez, Geraldine; Al-Bataineh, Sameer; Textor, Marcus

2014-02-01

Understanding of the interfacial chemistry of ultrathin polymeric adlayers is fundamentally important in the context of establishing quantitative design rules for the fabrication of nonfouling surfaces in various applications such as biomaterials and medical devices. In this study, seven poly(L-lysine)-graft-poly(2-methyl-2-oxazoline) (PLL-PMOXA) copolymers with grafting density (number of PMOXA chains per lysine residue) 0.09, 0.14, 0.19, 0.33, 0.43, 0.56, and 0.77, respectively, were synthesized and characterized by means of nuclear magnetic resonance spectroscopy (NMR). The copolymers were then adsorbed on Nb2O5 surfaces. Optical waveguide lightmode spectroscopy method was used to monitor the surface adsorption in situ of these copolymers and provide information on adlayer masses that were then converted into PLL and PMOXA surface densities. To investigate the relationship between copolymer bulk architecture (as shown by NMR data) and surface coverage as well as surface architecture, time-of-flight secondary ion mass spectrometry (ToF-SIMS) analysis was performed. Furthermore, ToF-SIMS method combined with principal component analysis (PCA) was used to verify the protein resistant properties of PLL-PMOXA adlayers, by thorough characterization before and after adlayer exposure to human serum. ToF-SIMS analysis revealed that the chemical composition as well as the architecture of the different PLL-PMOXA adlayers indeed reflects the copolymer bulk composition. ToF-SIMS results also indicated a heterogeneous surface coverage of PLL-PMOXA adlayers with high grafting densities higher than 0.33. In the case of protein resistant surface, PCA results showed clear differences between protein resistant and nonprotein-resistant surfaces. Therefore, ToF-SIMS results combined with PCA confirmed that the PLL-PMOXA adlayer with brush architecture resists protein adsorption. However, low increases of some amino acid signals in ToF-SIMS spectra were detected after the adlayer has been exposed to human serum.

Silencing of grapevine pectate lyase-like genes VvPLL2 and VvPLL3 confers resistance against Erysiphe necator and differentially modulates gene expression

USDA-ARS?s Scientific Manuscript database

Broad-spectrum resistance against powdery mildew (PM) has been reported by silencing susceptibility genes in the model plant Arabidopsis. Here we used artificial microRNA constructs in PM-susceptible Vitis vinifera cv. Chardonnay to stably silence two pectate lyase-like orthologs (VvPLL2 and VvPLL3)...

Synthesis and characterization of arginine-glycine-aspartic peptides conjugated poly(lactic acid-co-L-lysine) diblock copolymer.

PubMed

Yu, Hui; Guo, Xiaojuan; Qi, Xueliang; Liu, Peifeng; Shen, Xinyuan; Duan, Yourong

2008-03-01

A biodegradable Copolymer of poly(lactic acid-co-lysine)(PLA-PLL) was synthesized by a modified method and novel Arginine-Glycine-Aspartic (RGD) peptides were chemical conjugated to the primary epsilon-amine groups of lysine components in four steps: I to prepare the monomer of 3-(Nepsilon-benzoxycarbonyl-L-lysine)-6-L-methyl-2,5-morpholinedione; II to prepare diblock copolymer poly(lactic acid-co-(Z)-L-lysine) (PLA-PLL(Z)) by ring-opening polymerization of monomer and L,L-lactide with stannous octoate as initiator; III to prepare diblock copolymer PLA-PLL by deprotected the copolymer PLA-PLL(Z) in HBr/HoAc solution; IV the reaction between RGD and the primary epsilon-amine groups of the PLA-PLL. The structure of PLA-PLL-RGD and its precursors were conformed by FTIR-Raman and 1H NMR. Low weight average molecular weight (9,200 g/mol) of the PLA-PLL was obtained and its PDI is 1.33 determined by GPC. The PLA-PLL contained 2.1 mol% lysine groups as determined by 1H NMR using the lysine protecting group's phenyl protons. Therefore, the novel RGD-grafted diblock copolymer is expected to find application in drug carriers for tumor therapy or non-viral DNA carriers for gene therapy.

Wide Tuning Capability for Spacecraft Transponders

NASA Technical Reports Server (NTRS)

Lux, James; Mysoor, Narayan; Shah, Biren; Cook, Brian; Smith, Scott

2007-01-01

A document presents additional information on the means of implementing a capability for wide tuning of microwave receiver and transmitter frequencies in the development reported in the immediately preceding article, VCO PLL Frequency Synthesizers for Spacecraft Transponders (NPO- 42909). The reference frequency for a PLL-based frequency synthesizer is derived from a numerically controlled oscillator (NCO) implemented in digital logic, such that almost any reference frequency can be derived from a fixed crystal reference oscillator with microhertz precision. The frequency of the NCO is adjusted to track the received signal, then used to create another NCO frequency used to synthesize the transmitted signal coherent with, and at a specified frequency ratio to, the received signal. The frequencies can be changed, even during operation, through suitable digital programming. The NCOs and the related tracking loops and coherent turnaround logic are implemented in a field-programmable gate array (FPGA). The interface between the analog microwave receiver and transmitter circuits and the FPGA includes analog-to-digital and digital-toanalog converters, the sampling rates of which are chosen to minimize spurious signals and otherwise optimize performance. Several mixers and filters are used to properly route various signals.

Resonant Acoustic Determination of Complex Elastic Moduli

NASA Technical Reports Server (NTRS)

Brown, David A.; Garrett, Steven L.

1991-01-01

A simple, inexpensive, yet accurate method for measuring the dynamic complex modulus of elasticity is described. Using a 'free-free' bar selectively excited in three independent vibrational modes, the shear modulus is obtained by measuring the frequency of the torsional resonant mode and the Young's modulus is determined from measurement of either the longitudinal or flexural mode. The damping properties are obtained by measuring the quality factor (Q) for each mode. The Q is inversely proportional to the loss tangent. The viscoelastic behavior of the sample can be obtained by tracking a particular resonant mode (and thus a particular modulus) using a phase locked loop (PLL) and by changing the temperature of the sample. The change in the damping properties is obtained by measuring the in-phase amplitude of the PLL which is proportional to the Q of the material. The real and imaginary parts or the complex modulus can be obtained continuously as a function of parameters such as temperature, pressure, or humidity. For homogeneous and isotropic samples only two independent moduli are needed in order to characterize the complete set of elastic constants, thus, values can be obtained for the dynamic Poisson's ratio, bulk modulus, Lame constants, etc.

Climatology of GPS signal loss observed by Swarm satellites

NASA Astrophysics Data System (ADS)

Xiong, Chao; Stolle, Claudia; Park, Jaeheung

2018-04-01

By using 3-year global positioning system (GPS) measurements from December 2013 to November 2016, we provide in this study a detailed survey on the climatology of the GPS signal loss of Swarm onboard receivers. Our results show that the GPS signal losses prefer to occur at both low latitudes between ±5 and ±20° magnetic latitude (MLAT) and high latitudes above 60° MLAT in both hemispheres. These events at all latitudes are observed mainly during equinoxes and December solstice months, while totally absent during June solstice months. At low latitudes the GPS signal losses are caused by the equatorial plasma irregularities shortly after sunset, and at high latitude they are also highly related to the large density gradients associated with ionospheric irregularities. Additionally, the high-latitude events are more often observed in the Southern Hemisphere, occurring mainly at the cusp region and along nightside auroral latitudes. The signal losses mainly happen for those GPS rays with elevation angles less than 20°, and more commonly occur when the line of sight between GPS and Swarm satellites is aligned with the shell structure of plasma irregularities. Our results also confirm that the capability of the Swarm receiver has been improved after the bandwidth of the phase-locked loop (PLL) widened, but the updates cannot radically avoid the interruption in tracking GPS satellites caused by the ionospheric plasma irregularities. Additionally, after the PLL bandwidth increased larger than 0.5 Hz, some unexpected signal losses are observed even at middle latitudes, which are not related to the ionospheric plasma irregularities. Our results suggest that rather than 1.0 Hz, a PLL bandwidth of 0.5 Hz is a more suitable value for the Swarm receiver.

Design of a Humidity Sensor Tag for Passive Wireless Applications.

PubMed

Wu, Xiang; Deng, Fangming; Hao, Yong; Fu, Zhihui; Zhang, Lihua

2015-10-07

This paper presents a wireless humidity sensor tag for low-cost and low-power applications. The proposed humidity sensor tag, based on radio frequency identification (RFID) technology, was fabricated in a standard 0.18 μm complementary metal oxide semiconductor (CMOS) process. The top metal layer was deposited to form the interdigitated electrodes, which were then filled with polyimide as the humidity sensing layer. A two-stage rectifier adopts a dynamic bias-voltage generator to boost the effective gate-source voltage of the switches in differential-drive architecture, resulting in a flat power conversion efficiency curve. The capacitive sensor interface, based on phase-locked loop (PLL) theory, employs a simple architecture and can work with 0.5 V supply voltage. The measurement results show that humidity sensor tag achieves excellent linearity, hysteresis and stability performance. The total power-dissipation of the sensor tag is 2.5 μW, resulting in a maximum operating distance of 23 m under 4 W of radiation power of the RFID reader.

Design of a Humidity Sensor Tag for Passive Wireless Applications

PubMed Central

Wu, Xiang; Deng, Fangming; Hao, Yong; Fu, Zhihui; Zhang, Lihua

2015-01-01

This paper presents a wireless humidity sensor tag for low-cost and low-power applications. The proposed humidity sensor tag, based on radio frequency identification (RFID) technology, was fabricated in a standard 0.18 μm complementary metal oxide semiconductor (CMOS) process. The top metal layer was deposited to form the interdigitated electrodes, which were then filled with polyimide as the humidity sensing layer. A two-stage rectifier adopts a dynamic bias-voltage generator to boost the effective gate-source voltage of the switches in differential-drive architecture, resulting in a flat power conversion efficiency curve. The capacitive sensor interface, based on phase-locked loop (PLL) theory, employs a simple architecture and can work with 0.5 V supply voltage. The measurement results show that humidity sensor tag achieves excellent linearity, hysteresis and stability performance. The total power-dissipation of the sensor tag is 2.5 μW, resulting in a maximum operating distance of 23 m under 4 W of radiation power of the RFID reader. PMID:26457707

Harvesting and contamination control of microalgae Chlorella ellipsoidea using the bio-polymeric flocculant α-poly-l-lysine.

PubMed

Noh, Won; Kim, Jungmin; Lee, Sang-Jun; Ryu, Byung-Gon; Kang, Chang-Min

2018-02-01

Microalgae have been extensively studied for the production of various products. However, to date, microalgal biomass has not become economically feasible, mainly due to different issues such as contamination from various sources that occurs during downstream processes, and which leads to low quality biomass with limited application. In this study, to overcome contamination by flocculants and other microorganisms, the cationic biopolymer α-Poly-l-lysine (α-PLL) was applied. The cationic amine moiety and polymeric chain of α-PLL rendered microalgal harvesting efficient. With increasing α-PLL chain length, efficient dose- and time-dependent harvesting was achieved. In addition to efficient flocculation performance, biomass harvested using α-PLL showed suppressed biological contamination through the inherent antimicrobial activity of α-PLL. Thus, it is possible to upgrade the quality and storability of produced microalgal biomass using α-PLL-induced flocculation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Polylysine-modified polyethylenimine (PEI-PLL) mediated VEGF gene delivery protects dopaminergic neurons in cell culture and in rat models of Parkinson's Disease (PD).

PubMed

Sheikh, Muhammad Abid; Malik, Yousra Saeed; Xing, Zhenkai; Guo, Zhaopei; Tian, Huayu; Zhu, Xiaojuan; Chen, Xuesi

2017-05-01

Parkinson's Disease (PD) is a chronic neurodegenerative disorder characterized by motor deficits which result from the progressive loss of dopaminergic neurons. Gene therapy using growth factors such as VEGF seems to be a viable approach for potential therapeutic treatment of PD. In this study, we utilized a novel non-viral gene carrier designated as PEI-PLL synthesized by our laboratory to deliver VEGF gene to study its effect by using both cell culture as well as animal models of PD. For cell culture experiments, we utilized 6-hydroxydopamine (6-OHDA) mediated cell death model of MN9D cells following transfection with either a control plasmid or VEGF expressing plasmid. As compared to control transfected cells, PEI-PLL mediated VEGF gene delivery to MN9D cells resulted in increased cell viability, increase in the number of Tyrosine hydroxylase (TH) positive cells and decreased apoptosis following 6-OHDA insult. Next, we studied the therapeutic potential of PEI-PLL mediated VEGF gene delivery in SNPc by using unilateral 6-OHDA Medial forebrain bundle (MFB) lesion model of PD in rats. VEGF administration prevented the loss of motor functions induced by 6-OHDA as determined by behavior analysis. Similarly, VEGF inhibited the 6-OHDA mediated loss of DA neurons in Substantia Nigra Pars Compacta (SNPc) as well as DA nerve fibers in striatum as determined by TH immunostaining. In addition, PEI-PLL mediated VEGF gene delivery also prevented apoptosis and microglial activation in PD rat models. Together, these results clearly demonstrated the beneficial effects of PEI-PLL mediated VEGF gene delivery on dopaminergic system in both cell culture and animal models of PD. In this report, we exploited the potential of PEI-PLL to deliver VEGF gene for the potential therapeutic treatment of PD by using both cell culture and animal models of PD. To the best of our knowledge, this is the first report describing the use of novel polymeric gene carriers for the delivery of VEGF gene to DA neurons with improved transfection efficiency. Finally, the study will lead to a significant advancement in the field of non-viral PD gene therapy treatment. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Interaction of Poly(l-lysine)/Polysaccharide Complex Nanoparticles with Human Vascular Endothelial Cells.

PubMed

Weber, Dominik; Torger, Bernhard; Richter, Karsten; Nessling, Michelle; Momburg, Frank; Woltmann, Beatrice; Müller, Martin; Schwartz-Albiez, Reinhard

2018-05-23

Angiogenesis plays an important role in both soft and hard tissue regeneration, which can be modulated by therapeutic drugs. If nanoparticles (NP) are used as vectors for drug delivery, they have to encounter endothelial cells (EC) lining the vascular lumen, if applied intravenously. Herein the interaction of unloaded polyelectrolyte complex nanoparticles (PECNP) composed of cationic poly(l-lysine) (PLL) and various anionic polysaccharides with human vascular endothelial cells (HUVEC) was analyzed. In particular PECNP were tested for their cell adhesive properties, their cellular uptake and intracellular localization considering composition and net charge. PECNP may form a platform for both cell coating and drug delivery. PECNP, composed of PLL in combination with the polysaccharides dextran sulfate (DS), cellulose sulfate (CS) or heparin (HEP), either unlabeled or labeled with fluorescein isothiocyanate (FITC) and either with positive or negative net charge were prepared. PECNP were applied to human umbilical cord vein endothelial cells (HUVEC) in both, the volume phase and immobilized phase at model substrates like tissue culture dishes. The attachment of PECNP to the cell surface, their intracellular uptake, and effects on cell proliferation and growth behavior were determined. Immobilized PECNP reduced attachment of HUVEC, most prominently the systems PLL/HEP and PLL/DS. A small percentage of immobilized PECNP was taken up by cells during adhesion. PECNP in the volume phase showed no effect of the net charge sign and only minor effects of the composition on the binding and uptake of PECNP at HUVEC. PECNP were stored in endosomal vesicles in a cumulative manner without apparent further processing. During mitosis, internalized PECNP were almost equally distributed among the dividing cells. Both, in the volume phase and immobilized at the surface, PECNP composed of PLL/HEP and PLL/DS clearly reduced cell proliferation of HUVEC, however without an apparent cytotoxic effect, while PLL/CS composition showed minor impairment. PECNP have an anti-adhesive effect on HUVEC and are taken up by endothelial cells which may negatively influence the proliferation rate of HUVEC. The negative effects were less obvious with the composition PLL/CS. Since uptake and binding for PLL/HEP was more efficient than for PLL/DS, PECNP of PLL/HEP may be used to deliver growth factors to endothelial cells during vascularization of bone reconstitution material, whereas those of PLL/CS may have an advantage for substituting biomimetic bone scaffold material.

Morphometric Study of the Lumbar Posterior Longitudinal Ligament

PubMed Central

Lee, Sang Beom; Chang, Jae Chil; Lee, Gwang Soo; Hwang, Jae Chan; Bae, Hack Gun; Doh, Jae Won

2018-01-01

Objective Morphometric data for the lumbar posterior longitudinal ligament (PLL) was investigated to identify whether there is a difference in the morphometry of the PLL of the lumbar spine at each level with respect to the pattern of intervertebral disc displacement. Methods In 14 formalin-fixed adult cadavers (12 males and 2 females), from L1 to L5, the authors measured the width and height of the PLL and compared them with other landmarks such as the disc and the pedicle. Results Horizontally, at the upper margin of the disc, the central portion of the superficial PLL covered 17.8–36.9% of the disc width and the fan-like portion of the PLL covered 63.9–76.7% of the disc width. At the level of the median portion of the disc, the PLL covered 69.1–74.5% of the disc width. Vertically, at the level of the medial margin of the pedicle, the fan-like portion of the PLL covered 23.5–29.9% of the disc height. In general, a significant difference in length was not found in the right-left and male-female comparisons. Conclusion This study presents the morphometric data on the pattern of intervertebral disc displacement and helps to improve the knowledge of the surgical anatomy of the lumbar PLL. PMID:29354240

An Efficient Covalent Coating on Glass Slides for Preparation of Optical Oligonucleotide Microarrays

PubMed Central

Pourjahed, Atefeh; Rabiee, Mohammad; Tahriri, Mohammadreza

2013-01-01

Objective(s): Microarrays are potential analyzing tools for genomics and proteomics researches, which is in needed of suitable substrate for coating and also hybridization of biomolecules. Materials and Methods: In this research, a thin film of oxidized agarose was prepared on the glass slides which previously coated with poly-L-lysine (PLL). Some of the aldehyde groups of the activated agarose linked covalently to PLL amine groups; also bound to the amino groups of biomolecules. These linkages were fixed by UV irradiation. The prepared substrates were compared to only agarose-coated and PLL-coated slides. Results: Results on atomic force microscope (AFM) demonstrated that agarose provided three-dimensional surface which had higher loading and bindig capacity for biomolecules than PLL-coated surface which had two-dimensional surface. In addition, the signal-to-noise ratio in hybridization reactions performed on the agarose-PLL coated substrates increased two fold and four fold compared to agarose and PLL coated substrates, respectively. Conclusion: The agarose-PLL microarrays had the highest signal (2546) and lowest background signal (205) in hybridization, suggesting that the prepared slides are suitable in analyzing wide concentration range of analytes. PMID:24570832

Integrated genomic sequencing reveals mutational landscape of T-cell prolymphocytic leukemia

PubMed Central

Kiel, Mark J.; Velusamy, Thirunavukkarasu; Rolland, Delphine; Sahasrabuddhe, Anagh A.; Chung, Fuzon; Bailey, Nathanael G.; Schrader, Alexandra; Li, Bo; Li, Jun Z.; Ozel, Ayse B.; Betz, Bryan L.; Miranda, Roberto N.; Medeiros, L. Jeffrey; Zhao, Lili; Herling, Marco

2014-01-01

The comprehensive genetic alterations underlying the pathogenesis of T-cell prolymphocytic leukemia (T-PLL) are unknown. To address this, we performed whole-genome sequencing (WGS), whole-exome sequencing (WES), high-resolution copy-number analysis, and Sanger resequencing of a large cohort of T-PLL. WGS and WES identified novel mutations in recurrently altered genes not previously implicated in T-PLL including EZH2, FBXW10, and CHEK2. Strikingly, WGS and/or WES showed largely mutually exclusive mutations affecting IL2RG, JAK1, JAK3, or STAT5B in 38 of 50 T-PLL genomes (76.0%). Notably, gain-of-function IL2RG mutations are novel and have not been reported in any form of cancer. Further, high-frequency mutations in STAT5B have not been previously reported in T-PLL. Functionally, IL2RG-JAK1-JAK3-STAT5B mutations led to signal transducer and activator of transcription 5 (STAT5) hyperactivation, transformed Ba/F3 cells resulting in cytokine-independent growth, and/or enhanced colony formation in Jurkat T cells. Importantly, primary T-PLL cells exhibited constitutive activation of STAT5, and targeted pharmacologic inhibition of STAT5 with pimozide induced apoptosis in primary T-PLL cells. These results for the first time provide a portrait of the mutational landscape of T-PLL and implicate deregulation of DNA repair and epigenetic modulators as well as high-frequency mutational activation of the IL2RG-JAK1-JAK3-STAT5B axis in the pathogenesis of T-PLL. These findings offer opportunities for novel targeted therapies in this aggressive leukemia. PMID:24825865

Integrated genomic sequencing reveals mutational landscape of T-cell prolymphocytic leukemia.

PubMed

Kiel, Mark J; Velusamy, Thirunavukkarasu; Rolland, Delphine; Sahasrabuddhe, Anagh A; Chung, Fuzon; Bailey, Nathanael G; Schrader, Alexandra; Li, Bo; Li, Jun Z; Ozel, Ayse B; Betz, Bryan L; Miranda, Roberto N; Medeiros, L Jeffrey; Zhao, Lili; Herling, Marco; Lim, Megan S; Elenitoba-Johnson, Kojo S J

2014-08-28

The comprehensive genetic alterations underlying the pathogenesis of T-cell prolymphocytic leukemia (T-PLL) are unknown. To address this, we performed whole-genome sequencing (WGS), whole-exome sequencing (WES), high-resolution copy-number analysis, and Sanger resequencing of a large cohort of T-PLL. WGS and WES identified novel mutations in recurrently altered genes not previously implicated in T-PLL including EZH2, FBXW10, and CHEK2. Strikingly, WGS and/or WES showed largely mutually exclusive mutations affecting IL2RG, JAK1, JAK3, or STAT5B in 38 of 50 T-PLL genomes (76.0%). Notably, gain-of-function IL2RG mutations are novel and have not been reported in any form of cancer. Further, high-frequency mutations in STAT5B have not been previously reported in T-PLL. Functionally, IL2RG-JAK1-JAK3-STAT5B mutations led to signal transducer and activator of transcription 5 (STAT5) hyperactivation, transformed Ba/F3 cells resulting in cytokine-independent growth, and/or enhanced colony formation in Jurkat T cells. Importantly, primary T-PLL cells exhibited constitutive activation of STAT5, and targeted pharmacologic inhibition of STAT5 with pimozide induced apoptosis in primary T-PLL cells. These results for the first time provide a portrait of the mutational landscape of T-PLL and implicate deregulation of DNA repair and epigenetic modulators as well as high-frequency mutational activation of the IL2RG-JAK1-JAK3-STAT5B axis in the pathogenesis of T-PLL. These findings offer opportunities for novel targeted therapies in this aggressive leukemia. © 2014 by The American Society of Hematology.

An Integrated Hydrofoil and Propeller Design Tool for the Window (Trademark) Environment

DTIC Science & Technology

1996-06-01

Duui Code onto a angle ?w6crom& f Windows"’ basul application. Tbomis Supervimor hauuio E Kerwin rTk, Pioum o(Oo Esgmsurwiq 3 rwi•"* I S 4 S...adler funtow~ C.1. 1 PhePLI WinMain fiintion. 193 C. 1.2 The PU. F - -,-WndPfoc flaiction. 200 C. 1.3 The PLL WMCornwwd Hanudler ftuwtmL. 0 C.2 The PLL...34MW ISM~ p.J 3 lbm C.OW nd uma Jdlf Wehoinf Woo AMMse (A’MOVA I MIINeld baftf f 96) p2OM L. 13 I as hr as the screw propeller. Charles Babbage, an

Pelle Modulates dFoxO-Mediated Cell Death in Drosophila.

PubMed

Wu, Chenxi; Chen, Yujun; Wang, Feng; Chen, Changyan; Zhang, Shiping; Li, Chaojie; Li, Wenzhe; Wu, Shian; Xue, Lei

2015-10-01

Interleukin-1 receptor-associated kinases (IRAKs) are crucial mediators of the IL-1R/TLR signaling pathways that regulate the immune and inflammation response in mammals. Recent studies also suggest a critical role of IRAKs in tumor development, though the underlying mechanism remains elusive. Pelle is the sole Drosophila IRAK homolog implicated in the conserved Toll pathway that regulates Dorsal/Ventral patterning, innate immune response, muscle development and axon guidance. Here we report a novel function of pll in modulating apoptotic cell death, which is independent of the Toll pathway. We found that loss of pll results in reduced size in wing tissue, which is caused by a reduction in cell number but not cell size. Depletion of pll up-regulates the transcription of pro-apoptotic genes, and triggers caspase activation and cell death. The transcription factor dFoxO is required for loss-of-pll induced cell death. Furthermore, loss of pll activates dFoxO, promotes its translocation from cytoplasm to nucleus, and up-regulates the transcription of its target gene Thor/4E-BP. Finally, Pll physically interacts with dFoxO and phosphorylates dFoxO directly. This study not only identifies a previously unknown physiological function of pll in cell death, but also shed light on the mechanism of IRAKs in cell survival/death during tumorigenesis.

Dynamic tracking down-conversion signal processing method based on reference signal for grating heterodyne interferometer

NASA Astrophysics Data System (ADS)

Wang, Guochao; Yan, Shuhua; Zhou, Weihong; Gu, Chenhui

2012-08-01

Traditional displacement measurement systems by grating, which purely make use of fringe intensity to implement fringe count and subdivision, have rigid demands for signal quality and measurement condition, so they are not easy to realize measurement with nanometer precision. Displacement measurement with the dual-wavelength and single-grating design takes advantage of the single grating diffraction theory and the heterodyne interference theory, solving quite well the contradiction between large range and high precision in grating displacement measurement. To obtain nanometer resolution and nanometer precision, high-power subdivision of interference fringes must be realized accurately. A dynamic tracking down-conversion signal processing method based on the reference signal is proposed. Accordingly, a digital phase measurement module to realize high-power subdivision on field programmable gate array (FPGA) was designed, as well as a dynamic tracking down-conversion module using phase-locked loop (PLL). Experiments validated that a carrier signal after down-conversion can constantly maintain close to 100 kHz, and the phase-measurement resolution and phase precision are more than 0.05 and 0.2 deg, respectively. The displacement resolution and the displacement precision, corresponding to the phase results, are 0.139 and 0.556 nm, respectively.

pH-Amplified multilayer films based on hyaluronan: influence of HA molecular weight and concentration on film growth and stability.

PubMed

Shen, Liyan; Chaudouet, Patrick; Ji, Jian; Picart, Catherine

2011-04-11

In this study, we investigate the growth and internal properties of polyelectrolyte multilayer films made of poly(l-lysine) and hyaluronan (PLL/HA) under pH-amplified conditions, that is, by alternate deposition of PLL at high pH and HA at low pH. We focus especially on the influence of the molecular weight of HA in this process as well as on its concentration in solution. Film growth was followed by quartz crystal microbalance and by infrared spectroscopy to quantify the deposited mass and to characterize the internal properties of the films, including the presence of hydrogen bonds and the ionization degree of HA in the films. Film growth was significantly faster for HA of high molecular weight (1300 kDa) as compared with 400 and 200 kDa. PLL was found to exhibit a random structure once deposited in the films. Furthermore, we found that PLL-ending films are more stable when they are placed in PBS than their HA counterparts. This was explained on the basis of more cohesive interactions in the films for PLL-ending films. Finally, we quantified PLL(FITC) diffusion into the films and observed that PLL diffusion is enhanced when PLL is paired with the HA of high MW. All together, these results suggest that besides purely physicochemical parameters such as variation in pH, the molecular weight of HA, its concentration in solution, and the possibility to form intermolecular HA association play important roles in film growth, internal cohesion, and stability.

Interferon Inducers against Infectious Diseases

DTIC Science & Technology

1990-07-13

22 7. Induction of IFN in Micoe by IC-(PLL- monosaccharides ............................... *23 8. ICL- CDS04...seeking to replace both PLL and CM by modifying the PLL with engrafted polysaccharides . 2. Background A number of candidates have been developed in this...expanders, or being closely related to such. These include gelatin, anionically-modified gelatin, oarboxymethyl polysaocharides, sulfated polysaccharides

Mechanistic Differences in DNA Nanoparticle Formation in the Presence of Oligolysines and Poly-L-lysine†

PubMed Central

Nayvelt, Irina; Thomas, Thresia; Thomas, T. J.

2008-01-01

We studied the effectiveness of trilysine (Lys3)-, tetralysine (Lys4)-, pentalysine (Lys5)-, and poly-L-lysine (PLL) (MW: 50,000) on λ-DNA nanoparticle formation, and characterized the size, shape and stability of nanoparticles. Light scattering experiments showed EC50 (lysine concentration at 50% DNA compaction) values of ~0.0036, 2, and 20 μmoles/liter, respectively, for PLL, Lys5, and Lys4 at 10 mM [Na+]. Plots of log[EC50] versus log[Na+] showed positive slopes of 1.09 and 1.7, respectively, for Lys4 and Lys5 and a negative slope of −0.1 for PLL. Hydrodynamic radii of oligolysine-condensed particles increased (48–173 nm) with increasing [Na+], whereas no significant change occurred to nanoparticles formed with PLL. There was an increase in the size of nanoparticles formed with Lys5 at >40 °C, whereas no such change occurred with PLL. DNA melting temperature increased with oligolysine concentration. These results indicate distinct differences in the mechanism(s) by which oligolysines and PLL provoke DNA condensation to nanoparticles. PMID:17291071

Polypeptide multilayer films on colloidal particles: an in situ electro-optical study.

PubMed

Radeva, Tsetska; Kamburova, Kamelia

2007-04-15

The buildup of poly(L-glutamic acid) (PGA) and poly(L-lysine) (PLL) multilayers on beta-FeOOH colloidal particles was investigated by means of electro-optics and electrophoresis. The films were built at different (acidic) pH in the absence of salt. We found that the thickness of the film grows linearly when the fully charged PLL (at pH 5.5) is combined with almost fully charged PGA (at pH 6.5), with a thickness of about 2 nm per single layer. When the fully charged PLL is combined with weakly charged PGA (at pH 4.5), the film thickness increases exponentially with the number of deposited layers. The thickness of the exponentially growing film increases to 300 nm after deposition of 16 layers. The exponential film growth is attributed to the ability of the PLL to diffuse "in" and "out" of the film bulk at each deposition step. The variation in the electrical polarizability of the film-coated particles was also monitored as a function of the number of adsorbed layers. The result reveals that the PLL chains, which can diffuse into the film bulk, have no measurable contribution to the electro-optical effect of the films terminated with PLL. It is only due to the polarization of counterions of the PLL adsorbed on the film surface.

A mPEG-PLGA-b-PLL copolymer carrier for adriamycin and siRNA delivery.

PubMed

Liu, Peifeng; Yu, Hui; Sun, Ying; Zhu, Mingjie; Duan, Yourong

2012-06-01

A amphiphilic block copolymer composed of conventional monomethoxy (polyethylene glycol)-poly (d,l-lactide-co-glycolide)-poly (l-lysine) (mPEG-PLGA-b-PLL) was synthesized. The chemical structure of this copolymer and its precursors was confirmed by Fourier Transform Infrared Spectroscopy (FTIR), (1)H Nuclear Magnetic Resonance ((1)H NMR) and Gel Permeation Chromatography (GPC). The copolymer was used to prepare nanoparticles (NPs) that were then loaded with either the anti-cancer drug adriamycin or small interfering RNA-negative (siRNA) using a double emulsion method. MTT assays used to study the in vitro cytotoxicity of mPEG-PLGA-b-PLL NPs showed that these particles were not toxic in huh-7 hepatic carcinoma cells. Confocal laser scanning microscopy (CLSM) and flow cytometer analysis results demonstrated efficient mPEG-PLGA-b-PLL NPs-mediated delivery of both adriamycin and siRNA into the cells. In vivo the targeting delivery of adriamycin or siRNA mediated by mPEG-PLGA-b-PLL NPs in the huh-7 hepatic carcinoma-bearing mice was evaluated using a fluorescence imaging system. The targeting delivery results and froze section analysis confirmed that drug or siRNA is deliver to tumor more efficiently by mPEG-PLGA-b-PLL NPs than free drug or Lipofectamine™2000. The high efficiency delivery of mPEG-PLGA-b-PLL NPs mainly due to the enhancement of cellular uptake. These results imply that mPEG-PLGA-b-PLL NPs have a great potential to be used as an effective carriers for adriamycin or siRNA. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Are structural properties of dendrimers sensitive to the symmetry of branching? Computer simulation of lysine dendrimers

NASA Astrophysics Data System (ADS)

Falkovich, S.; Markelov, D.; Neelov, I.; Darinskii, A.

2013-08-01

Poly-L-lysine (PLL) dendrimers are promising systems for biomedical applications due to their biocompatibility. These dendrimers have a specific topology: two spacers of different lengths come out of each branching point and thus the branching is asymmetric. Because of this asymmetry terminal groups are located at branches of different lengths, unlike dendrimers with a symmetric branching. This paper presents the results of the first systematic molecular dynamics simulation of such asymmetric PLL dendrimers. It is shown that PLL dendrimers are porous molecules with all terminal groups equally accessible to water. We have found that in spite of an asymmetry of branching the general structural characteristics of PLL dendrimers are rather similar to those of dendrimers with symmetric branching. We have also found that the structural characteristics of PLL dendrimers obey the general laws for dendrimers and that their electrostatic properties agree with the predictions of a general analytic theory.

Laser Linewidth Requirements for Optical Bpsk and Qpsk Heterodyne Lightwave Systems.

NASA Astrophysics Data System (ADS)

Boukli-Hacene, Mokhtar

In this dissertation, optical Binary Phase-Shift Keying (BPSK) and Quadrature Phase-Shift Keying (QPSK) heterodyne communication receivers are investigated. The main objective of this research work is to analyze the performance of these receivers in the presence of laser phase noise and shot noise. The heterodyne optical BPSK is based on the square law carrier recovery (SLCR) scheme for phase detection. The BPSK heterodyne receiver is analyzed assuming a second order linear phase-locked loop (PLL) subsystem and a small phase error. The noise properties are analyzed and the problem of minimizing the effect of noise is addressed. The performance of the receiver is evaluated in terms of the bit error rate (BER), which leads to the analysis of the BER versus the laser linewidth and the number of photons/bit to achieve good performance. Since we cannot track the pure carrier component in the presence of noise, a non-linear model is used to solve the problem of recovery of the carrier. The non -linear system is analyzed in the presence of a low signal -to-noise ratio (SNR). The non-Gaussian noise model represented by its probability density function (PDF) is used to analyze the performance of the receiver, especially the phase error. In addition the effect of the PLL is analyzed by studying the cycle slippage (cs). Finally, the research effort is expanded from BPSK to QPSK systems. The heterodyne optical QPSK based on the fourth power multiplier scheme (FPMS) in conjunction with linear and non-linear PLL model is investigated. Optimum loop and higher power penalty in the presence of phase noise and shot noise are analyzed. It is shown that the QPSK system yields a high speed and high sensitivity coherent means for transmission of information accompanied by a small degradation in the laser linewidth. Comparative analysis of BPSK and QPSK systems leads us to conclude that in terms of laser linewidth, bit rate, phase error and power penalty, the QPSK system is more sensitive than the BPSK system and suffers less from higher power penalty. The BPSK and QPSK heterodyne receivers used in the uncoded scheme demand a realistic laser linewidth. Since the laser linewidth is the critical measure of the performance of a receiver, a convolutional code applied to QPSK of the system is used to improve the sensitivity of the system. The effect of coding is particularly important as means of relaxing the laser linewidth requirement. The validity and usefulness of the analysis presented in the dissertation is supported by computer simulations.

A CMOS 0.18 μm 600 MHz clock multiplier PLL and a pseudo-LVDS driver for the high speed data transmission for the ALICE Inner Tracking System front-end chip

NASA Astrophysics Data System (ADS)

Lattuca, A.; Mazza, G.; Aglieri Rinella, G.; Cavicchioli, C.; Chanlek, N.; Collu, A.; Degerli, Y.; Dorokhov, A.; Flouzat, C.; Gajanana, D.; Gao, C.; Guilloux, F.; Hillemanns, H.; Hristozkov, S.; Junique, A.; Keil, M.; Kim, D.; Kofarago, M.; Kugathasan, T.; Kwon, Y.; Mager, M.; Sielewicz, K. Marek; Marin Tobon, C. Augusto; Marras, D.; Martinengo, P.; Mugnier, H.; Musa, L.; Pham, T. Hung; Puggioni, C.; Reidt, F.; Riedler, P.; Rousset, J.; Siddhanta, S.; Snoeys, W.; Song, M.; Usai, G.; Van Hoorne, J. Willem; Yang, P.

2016-01-01

This work presents the 600 MHz clock multiplier PLL and the pseudo-LVDS driver which are two essential components of the Data Transmission Unit (DTU), a fast serial link for the 1.2 Gb/s data transmission of the ALICE inner detector front-end chip (ALPIDE). The PLL multiplies the 40 MHz input clock in order to obtain the 600 MHz and the 200 MHz clock for a fast serializer which works in Double Data Rate mode. The outputs of the serializer feed the pseudo-LVDS driver inputs which transmits the data from the pixel chip to the patch panel with a limited number of signal lines. The driver drives a 5.3 m-6.5 m long differential transmission line by steering a maximum of 5 mA of current at the target speed. To overcome bandwidth limitations coming from the long cables the pre-emphasis can be applied to the output. Currents for the main and pre-emphasis driver can individually be adjusted using on-chip digital-to-analog converters. The circuits will be integrated in the pixel chip and are designed in the same 0.18 μm CMOS technology and will operate from the same 1.8 V supply. Design and test results of both circuits are presented.

Impact of ion binding on poly-L-lysine (un)folding energy landscape and kinetics.

PubMed

Xiong, Kan; Asher, Sanford A

2012-06-21

We utilize T-jump UV resonance Raman spectroscopy (UVRR) to study the impact of ion binding on the equilibrium energy landscape and on (un)folding kinetics of poly-L-lysine (PLL). We observe that the relaxation rates of the folded conformations (including π-helix (bulge), pure α-helix, and turns) of PLL are slower than those of short alanine-based peptides. The PLL pure α-helix folding time is similar to that of short alanine-based peptides. We for the first time have directly observed that turn conformations are α-helix and π-helix (bulge) unfolding intermediates. ClO(4)(-) binding to the Lys side chain -NH(3)(+) groups and the peptide backbone slows the α-helix unfolding rate compared to that in pure water, but little impacts the folding rate, resulting in an increased α-helix stability. ClO(4)(-) binding significantly increases the PLL unfolding activation barrier but little impacts the folding barrier. Thus, the PLL folding coordinate(s) differs from the unfolding coordinate(s). The-π helix (bulge) unfolding and folding coordinates do not directly go through the α-helix energy well. Our results clearly demonstrate that PLL (un)folding is not a two-state process.

Weak and Dynamic GNSS Signal Tracking Strategies for Flight Missions in the Space Service Volume

PubMed Central

Jing, Shuai; Zhan, Xingqun; Liu, Baoyu; Chen, Maolin

2016-01-01

Weak-signal and high-dynamics are of two primary concerns of space navigation using GNSS (Global Navigation Satellite System) in the space service volume (SSV). The paper firstly defines a reference assumption third-order phase-locked loop (PLL) as the baseline of an onboard GNSS receiver, and proves the incompetence of this conventional architecture. Then an adaptive four-state Kalman filter (KF)-based algorithm is introduced to realize the optimization of loop noise bandwidth, which can adaptively regulate its filter gain according to the received signal power and line-of-sight (LOS) dynamics. To overcome the matter of losing lock in weak-signal and high-dynamic environments, an open loop tracking strategy aided by an inertial navigation system (INS) is recommended, and the traditional maximum likelihood estimation (MLE) method is modified in a non-coherent way by reconstructing the likelihood cost function. Furthermore, a typical mission with combined orbital maneuvering and non-maneuvering arcs is taken as a destination object to test the two proposed strategies. Finally, the experiment based on computer simulation identifies the effectiveness of an adaptive four-state KF-based strategy under non-maneuvering conditions and the virtue of INS-assisted methods under maneuvering conditions. PMID:27598164

Weak and Dynamic GNSS Signal Tracking Strategies for Flight Missions in the Space Service Volume.

PubMed

Jing, Shuai; Zhan, Xingqun; Liu, Baoyu; Chen, Maolin

2016-09-02

Weak-signal and high-dynamics are of two primary concerns of space navigation using GNSS (Global Navigation Satellite System) in the space service volume (SSV). The paper firstly defines a reference assumption third-order phase-locked loop (PLL) as the baseline of an onboard GNSS receiver, and proves the incompetence of this conventional architecture. Then an adaptive four-state Kalman filter (KF)-based algorithm is introduced to realize the optimization of loop noise bandwidth, which can adaptively regulate its filter gain according to the received signal power and line-of-sight (LOS) dynamics. To overcome the matter of losing lock in weak-signal and high-dynamic environments, an open loop tracking strategy aided by an inertial navigation system (INS) is recommended, and the traditional maximum likelihood estimation (MLE) method is modified in a non-coherent way by reconstructing the likelihood cost function. Furthermore, a typical mission with combined orbital maneuvering and non-maneuvering arcs is taken as a destination object to test the two proposed strategies. Finally, the experiment based on computer simulation identifies the effectiveness of an adaptive four-state KF-based strategy under non-maneuvering conditions and the virtue of INS-assisted methods under maneuvering conditions.

Fabrication and design of bioactive agent coated, highly-aligned electrospun matrices for nerve tissue engineering: Preparation, characterization and application

NASA Astrophysics Data System (ADS)

Lee, Sang Jin; Heo, Min; Lee, Donghyun; Heo, Dong Nyoung; Lim, Ho-Nam; Kwon, Il Keun

2017-12-01

In this study, we designed highly-aligned thermoplastic polycarbonate urethane (PCU) fibrous scaffolds coated with bioactive compounds, such as Poly-L-Lysine (PLL) and Poly-L-Ornithine (PLO), to enhance cellular adhesion and directivity. These products were characterized by scanning electron microscope (SEM) analysis which demonstrated that highly aligned fiber strands were formed without beads when coated onto a mandrel rotating at 1800 rpm. During in vitro cell test, PLO-coated, aligned PCU scaffolds were found to have significantly higher proliferation rates than PLL coated and bare PCU scaffolds. Interestingly, dental pulp stem cells (DPSCs) were observed to stretch along the longitudinal axis parallel to the cell direction on highly aligned scaffolds. These results clearly confirm that our strategy may suggest a useful paradigm by inducing neural tissue repair as a means to remodeling and healing of tissue for restorative procedures in neural tissue engineering.

Frequency-Locked Detector Threshold Setting Criteria Based on Mean-Time-To-Lose-Lock (MTLL) for GPS Receivers

PubMed Central

Zhao, Na; Qin, Honglei; Sun, Kewen; Ji, Yuanfa

2017-01-01

Frequency-locked detector (FLD) has been widely utilized in tracking loops of Global Positioning System (GPS) receivers to indicate their locking status. The relation between FLD and lock status has been seldom discussed. The traditional PLL experience is not suitable for FLL. In this paper, the threshold setting criteria for frequency-locked detector in the GPS receiver has been proposed by analyzing statistical characteristic of FLD output. The approximate probability distribution of frequency-locked detector is theoretically derived by using a statistical approach, which reveals the relationship between probabilities of frequency-locked detector and the carrier-to-noise ratio (C/N0) of the received GPS signal. The relationship among mean-time-to-lose-lock (MTLL), detection threshold and lock probability related to C/N0 can be further discovered by utilizing this probability. Therefore, a theoretical basis for threshold setting criteria in frequency locked loops for GPS receivers is provided based on mean-time-to-lose-lock analysis. PMID:29207546

Frequency-Locked Detector Threshold Setting Criteria Based on Mean-Time-To-Lose-Lock (MTLL) for GPS Receivers.

PubMed

Jin, Tian; Yuan, Heliang; Zhao, Na; Qin, Honglei; Sun, Kewen; Ji, Yuanfa

2017-12-04

Frequency-locked detector (FLD) has been widely utilized in tracking loops of Global Positioning System (GPS) receivers to indicate their locking status. The relation between FLD and lock status has been seldom discussed. The traditional PLL experience is not suitable for FLL. In this paper, the threshold setting criteria for frequency-locked detector in the GPS receiver has been proposed by analyzing statistical characteristic of FLD output. The approximate probability distribution of frequency-locked detector is theoretically derived by using a statistical approach, which reveals the relationship between probabilities of frequency-locked detector and the carrier-to-noise ratio ( C / N ₀) of the received GPS signal. The relationship among mean-time-to-lose-lock (MTLL), detection threshold and lock probability related to C / N ₀ can be further discovered by utilizing this probability. Therefore, a theoretical basis for threshold setting criteria in frequency locked loops for GPS receivers is provided based on mean-time-to-lose-lock analysis.

Modeling and simulation of continuous wave velocity radar based on third-order DPLL

NASA Astrophysics Data System (ADS)

Di, Yan; Zhu, Chen; Hong, Ma

2015-02-01

Second-order digital phase-locked-loop (DPLL) is widely used in traditional Continuous wave (CW) velocity radar with poor performance in high dynamic conditions. Using the third-order DPLL can improve the performance. Firstly, the echo signal model of CW radar is given. Secondly, theoretical derivations of the tracking performance in different velocity conditions are given. Finally, simulation model of CW radar is established based on Simulink tool. Tracking performance of the two kinds of DPLL in different acceleration and jerk conditions is studied by this model. The results show that third-order PLL has better performance in high dynamic conditions. This model provides a platform for further research of CW radar.

Method for digital measurement of phase-frequency characteristics for a fixed-length ultrasonic spectrometer

NASA Astrophysics Data System (ADS)

Astashev, M. E.; Belosludtsev, K. N.; Kharakoz, D. P.

2014-05-01

One of the most accurate methods for measuring the compressibility of liquids is resonance measurement of sound velocity in a fixed-length interferometer. This method combines high sensitivity, accuracy, and small sample volume of the test liquid. The measuring principle is to study the resonance properties of a composite resonator that contains a test liquid sample. Ealier, the phase-locked loop (PLL) scheme was used for this. In this paper, we propose an alternative measurement scheme based on digital analysis of harmonic signals, describe the implementation of this scheme using commercially available data acquisition modules, and give examples of test measurements with accuracy evaluations of the results.

A Novel Fucose-binding Lectin from Photorhabdus luminescens (PLL) with an Unusual Heptabladed β-Propeller Tetrameric Structure*

PubMed Central

Kumar, Atul; Sýkorová, Petra; Demo, Gabriel; Dobeš, Pavel; Hyršl, Pavel

2016-01-01

Photorhabdus luminescens is known for its symbiosis with the entomopathogenic nematode Heterorhabditis bacteriophora and its pathogenicity toward insect larvae. A hypothetical protein from P. luminescens was identified, purified from the native source, and characterized as an l-fucose-binding lectin, named P. luminescens lectin (PLL). Glycan array and biochemical characterization data revealed PLL to be specific toward l-fucose and the disaccharide glycan 3,6-O-Me2-Glcβ1–4(2,3-O-Me2)Rhaα-O-(p-C6H4)-OCH2CH2NH2. PLL was discovered to be a homotetramer with an intersubunit disulfide bridge. The crystal structures of native and recombinant PLL revealed a seven-bladed β-propeller fold creating seven putative fucose-binding sites per monomer. The crystal structure of the recombinant PLL·l-fucose complex confirmed that at least three sites were fucose-binding. Moreover, the crystal structures indicated that some of the other sites are masked either by the tetrameric nature of the lectin or by incorporation of the C terminus of the lectin into one of these sites. PLL exhibited an ability to bind to insect hemocytes and the cuticular surface of a nematode, H. bacteriophora. PMID:27758853

Infiltration of the thyroid gland by T-cell prolymphocytic leukemia.

PubMed

Fujiwara, Kazunori; Fukuhara, Takahiro; Kitano, Hiroya; Okazaki, Toshiro

2014-08-01

T-cell prolymphocytic leukemia (T-PLL) is rare, accounting for only 0.06% of all malignant lymphomas, and is classified as a T-cell mature lymphoma. The disease affects mainly elderly patients and is characterized by splenomegaly, lymphadenopathy, skin infiltration, and a high leukocyte count, but thyroid filtration has never been detected as far as we could determine. We report here a case of infiltration of the thyroid gland by T-PLL. An 89-year-old woman who had been treated for Hashimoto's thyroiditis for 20 years presented with a progressively enlarging thyroid mass accompanied by dyspnea and dysphasia. Atypical lymphocytes with irregular nuclei were observed in the peripheral blood. An open biopsy of the thyroid provided pathological evidence of T-PLL, and bone marrow examination showed infiltration by T-PLL. The diagnosis was therefore infiltration of the thyroid gland by T-PLL. Chemotherapy was initiated, but six months after termination, recurrence of neck swelling was observed. The patient was then treated with radiotherapy, but she died of a major stroke 15 months after onset. This is the first report of T-PLL infiltration of the thyroid gland, reminding physicians to keep in mind a broad differential diagnosis when encountering a patient with diffuse thyroid lesions and abnormal lymphocytes in the peripheral blood.

Influence of poly(L-lysine) on the structure of dipalmitoylphosphatidylglycerol/water dispersions studied by X-ray scattering.

PubMed

Förster, G; Schwieger, C; Faber, F; Weber, T; Blume, A

2007-04-01

The interaction between the negatively charged phospholipid DPPG and positively charged poly(L: -lysine) (PLL) of different lengths was studied by X-ray scattering in the SAXS and WAXS region. As a reference pure DPPG (Na salt) was investigated over a wide temperature range (-30 to 70 degrees C). The phase behavior of DPPG in aqueous and in buffer/salt dispersions showed a metastable subgel phase at low temperatures and a recrystallization upon heating before reaching the liquid-crystalline phase. The presence of additional salt stabilizes the bilayer structure and decreases the recrystallization temperature. Large changes in the SAXS region are not connected with changes in chain packing. In DPPG/PLL samples, the PLL is inserted between adjacent headgroup layers and liberates counterions which give rise to a freezing point depression. In the complex with DPPG PLL form an alpha-helical secondary structure at pH 7 and temperatures below the gel to liquid-crystalline phase transition. This prevents DPPG from recrystallization and strongly increases the stacking order. The lamellar repeat distance is decreased and fixed by the helix conformation of PLL in the gel phase. PLL with n = 14 is too short to form helices and is squeezed out reversibly from the interbilayer space upon cooling by freezing of trapped water. In dispersions with longer PLLs (n > 400) at -20 degrees C a 1D crystallization of PLL alpha-helices in the aqueous layer between the headgroups takes place. A structural model is presented for the lateral periodic complex, which is similar to the known cationic lipid/DNA complex.

A novel architecture of recovered data comparison for high speed clock and data recovery

NASA Astrophysics Data System (ADS)

Gao, Susan; Li, Fei; Wang, Zhigong; Cui, Hongliang

2005-05-01

A clock and data recovery (CDR) circuit is one of the crucial blocks in high-speed serial link communication systems. The data received in these systems are asynchronous and noisy, requiring that a clock be extracted to allow synchronous operations. Furthermore, the data must be "retimed" so that the jitter accumulated during transmission is removed. This paper presents a novel architecture of CDR, which is very tolerant to long sequences of serial ones or zeros and also robust to occasional long absence of transitions. The design is based on the fact that a basic clock recovery having a clock recovery circuit (CRC) and a data decision circuit separately would generate a high jitter clock when the received non-return-to-zero (NRZ) data with long sequences of ones or zeros. To eliminate this drawback, the proposed architecture incorporates a data circuit decision circuit within the phase-locked loop (PLL) CRC. Other than this, a new phase detector (PD) is also proposed, which was easy to accomplish and robust at high speed. This PD is functional with a random input and automatically turns to disable during both the locked state and long absence of transitions. The voltage-controlled oscillator (VCO) is also designed delicately to suppress the jitter. Due to the high stability, the jitter is highly reduced when the loop is locked. The simulation results of such CDR working at 1.25Gb/s particularly for 1000BASE-X Gigabit Ethernet by using TSMC 0.25μm technology are presented to prove the feasibility of this architecture. One more CDR based on edge detection architecture is also built in the circuit for performance comparisons.

Internalization and Subcellular Trafficking of Poly-l-lysine Dendrimers Are Impacted by the Site of Fluorophore Conjugation.

PubMed

Avaritt, Brittany R; Swaan, Peter W

2015-06-01

Internalization and intracellular trafficking of dendrimer-drug conjugates play an important role in achieving successful drug delivery. In this study, we aimed to elucidate the endocytosis mechanisms and subcellular localization of poly-l-lysine (PLL) dendrimers in Caco-2 cells. We also investigated the impact of fluorophore conjugation on cytotoxicity, uptake, and transepithelial transport. Oregon green 514 (OG) was conjugated to PLL G3 at either the dendrimer periphery or the core. Chemical inhibitors of clathrin-, caveolin-, cholesterol-, and dynamin-mediated endocytosis pathways and macropinocytosis were employed to establish internalization mechanisms, while colocalization with subcellular markers was used to determine dendrimer trafficking. Cell viability, internalization, and uptake were all influenced by the site of fluorophore conjugation. Uptake was found to be highly dependent on cholesterol- and dynamin-mediated endocytosis as well as macropinocytosis. Dendrimers were trafficked to endosomes and lysosomes, and subcellular localization was impacted by the fluorophore conjugation site. The results of this study indicate that PLL dendrimers exploit multiple pathways for cellular entry, and internalization and trafficking can be impacted by conjugation. Therefore, design of dendrimer-drug conjugates requires careful consideration to achieve successful drug delivery.

Interaction of anesthetic molecules with α-helix and polyproline II extended helix of long-chain poly-L-lysine

NASA Astrophysics Data System (ADS)

Cieślik-Boczula, Katarzyna; Rospenk, Maria

2018-01-01

The effect of halothane, enflurane, sevoflurane, and isoflurane molecules, as volatile anesthetics, on the α-helices and polyproline II extended helices (PPII) of long-chain poly-L-lysine (PLL) were studied using Fourier-transform infrared and vibrational circular dichroism spectroscopy. Uncharged and charged α-helices, as well as charged extended PPII helices, were subjected to anesthetic actions in solvents with different pD values or methanol to water ratios. A crucial factor responsible for hindering the anesthetic-PLL interactions is shown to be the ionization of amino groups of the PLL side chains. The α-helix to β-sheet transition was triggered only for the uncharged α-helical structures of PLL by the nonpolar anesthetics under study.

Study on relationship between expression level and molecular conformations of gene drugs targeting to hepatoma cells in vitro

PubMed Central

Yang, Dong-Ye; Lu, Fang-Gen; Tang, Xi-Xiang; Zhao, Shui-Ping; Ouyang, Chun-Hui; Wu, Xiao-Ping; Liu, Xiao-Wei; Wu, Xiao-Ying

2003-01-01

AIM: To increase exogenous gene expression level by modulating molecular conformations of targeting gene drugs. METHODS: The full length cDNAs of both P40 and P35 subunits of human interleukin 12 were amplified through polymerase chain reaction (PCR) and cloned into eukaryotic expressing vectors pcDNA3.1 (±) to construct plasmids of P (+)/IL-12, P (+)/P40 and P (-)/P35. These plasmids were combined with ASOR-PLL to form two targeting gene drugs [ASOR-PLL-P (+)/IL-12 and ASOR-PLL-P (+)/P40 + ASOR-PLL-P (-)/P35] in optimal ratios. The conformations of these two drugs at various concentrations adjuvant were examined under electron microscope (EM) and the drugs were transfected into HepG2 (ASGr+) cells. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed with total RNA extracted from the transfected cells to determine the hIL12 mRNA transcript level. The hIL12 protein in the cultured supernatant was measured with enzyme-linked immunosorbent assay (ELISA) 48 hours after transfection. RESULTS: Targeting gene drugs, whose structures were granular and circle-like and diameters ranged from 25 nm to 150 nm, had the highest hIL-12 expression level. The hIL-12 expression level in the group co-transfected with ASOR-PLL-P (+)/P40 and ASOR-PLL-P (-)/P35 was higher than that of ASOR-PLL-P (+)/IL-12 transfected group. CONCLUSION: The molecular conformations of targeting gene drugs play an important role in exogenous gene expression level, the best structures are granular and circle-like and their diameters range from 25 nm to 150 nm. The sizes and linking styles of exogenous genes also have some effects on their expression level. PMID:12970883

Flexion-rotation manoeuvre increases dimension of the acoustic target window for paramedian thoracic epidural access.

PubMed

Ramsay, N; Walker, J; Tang, R; Vaghadia, H; Sawka, A

2014-03-01

The posterior longitudinal ligament (PLL) has been found to be a reliable measure of the acoustic target window for lumbar spinal anaesthesia and a predictive tool for difficult spinals. Currently, there is limited information on the PLL in the thoracic spine and its potential use for optimizing the acoustic target window during thoracic epidural placement. This study examined the effects of changes in body position on the length of the PLL as a measure of the acoustic target window for paramedian thoracic epidural access. We performed thoracic ultrasonography on 30 adult volunteers to measure the length of the PLL at the T9/10 interspace, in five different positions: P1, neutral; P2, thoracic and lumbar flexion; P3, as in position 2 with dorsal table tilt to 10°; P4, as in position 2 with 45° rightward shoulder rotation; and P5, as in position 2 with 45° leftward shoulder rotation. The mean (sd) PLL length increased significantly from 9.9 (3.9) mm in P1 to 11.7 (3.4) mm in P2, 12.9 (3.1) mm in P3, and 13.8 (4.0) mm in P4 (P<0.01, <0.01, and <0.01, respectively). The mean PLL length in P3 and P4 was also significantly longer compared with P2 (P<0.01 and 0.01, respectively). In volunteers, flexion with 10° dorsal table tilt and flexion with right rotation significantly increased the length of the ipsilateral PLL, compared with the standard flexed sitting position, as visualized by paramedian ultrasonography at the level of T9/10.

Specific gene transfer mediated by galactosylated poly-L-lysine into hepatoma cells.

PubMed

Han, J; Il Yeom, Y

2000-07-20

Plasmid DNA/galactosylated poly-L-lysine(GalPLL) complex was used to transfer luciferase reporter gene in vitro into human hepatoma cells by a receptor-mediated endocytosis process. DNA was combined with galPLL via charge interaction (DNA:GalPLL:fusogenic peptide, 1:0.4:5, w/w/w) and the resulting complex was characterized by dynamic light scattering, gel retardation assay and zeta potential analyzer to determine the particle size, electrostatic charge interaction, and apparent surface charge. The complex was tested for the efficiency of gene transfer in cultured human hepatoblastoma cell line Hep G2 and fibroblast cells NIH/3T3 in vitro. The mean diameter of the complex (DNA:GalPLL=1:0.4, w/w) was 256+/-34.8 nm, and at this ratio, it was positively charged (zeta potential of this complex was 10.1 mV). Hep G2 cells, which express a galactose specific membrane lectin, were efficiently and selectively transfected with the RSV Luc/GalPLL complex in a sugar-dependent manner. NIH/3T3 cells, which do not express the galactose-specific membrane lectin, showed only a marginal level of gene expression. The transfection efficiency of GalPLL-conjugated DNA complex into Hep G2 cells was greatly enhanced in the presence of fusogenic peptide that can disrupt endosomes, where the GalPLL-DNA complex is entrapped with the fusogenic peptide. With the fusogenic peptide KALA, the luciferase activity in Hep G2 cells was ten-fold higher than that of cells transfected in the absence of the fusogenic peptide. Our gene transfer formulation may find potential application for the gene therapy of liver diseases.

The Modification of siRNA with 3′ Cholesterol to Increase Nuclease Protection and Suppression of Native mRNA by Select siRNA Polyplexes

PubMed Central

Ambardekar, Vishakha V.; Han, Huai-Yun; Varney, Michelle L.; Vinogradov, Serguei V.; Singh, Rakesh K.; Vetro, Joseph A.

2010-01-01

Polymer-siRNA complexes (siRNA polyplexes) are being actively developed to improve the therapeutic application of siRNA. A major limitation for many siRNA polyplexes, however, is insufficient mRNA suppression. Given that modifying the sense strand of siRNA with 3′ cholesterol (chol-siRNA) increases the activity of free nuclease-resistant siRNA in vitro and in vivo, we hypothesized that complexation of chol-siRNA can increase mRNA suppression by siRNA polyplexes. In this study, the characteristics and siRNA activity of self assembled polyplexes formed with chol-siRNA or unmodified siRNA were compared using three types of conventional, positively charged polymers: (i) biodegradable, cross-linked nanogels (BDNG) (ii) graft copolymers (PEI-PEG), and (iii) linear block copolymers (PLL10-PEG, and PLL50-PEG). Chol-siRNA did not alter complex formation or the resistance of polyplexes to siRNA displacement by heparin but increased nuclease protection by BDNG, PLL10-PEG, and PLL50-PEG polyplexes over polyplexes with unmodified siRNA. Chol-CYPB siRNA increased suppression of native CYPB mRNA in mammary microvascular endothelial cells (MVEC) by BDNG polyplexes (35%) and PLL10-PEG polyplexes (69%) over comparable CYPB siRNA polyplexes but had no effect on PEI-PEG or PLL50-PEG polyplexes. Overall, these results indicate that complexation of chol-siRNA increases nuclease protection and mRNA suppression by select siRNA polyplexes. These results also suggest that polycationic block length is an important factor in increasing mRNA suppression by PLL-PEG chol-siRNA polyplexes in mammary MVEC. PMID:21047680

The modification of siRNA with 3' cholesterol to increase nuclease protection and suppression of native mRNA by select siRNA polyplexes.

PubMed

Ambardekar, Vishakha V; Han, Huai-Yun; Varney, Michelle L; Vinogradov, Serguei V; Singh, Rakesh K; Vetro, Joseph A

2011-02-01

Polymer-siRNA complexes (siRNA polyplexes) are being actively developed to improve the therapeutic application of siRNA. A major limitation for many siRNA polyplexes, however, is insufficient mRNA suppression. Given that modifying the sense strand of siRNA with 3' cholesterol (chol-siRNA) increases the activity of free nuclease-resistant siRNA in vitro and in vivo, we hypothesized that complexation of chol-siRNA can increase mRNA suppression by siRNA polyplexes. In this study, the characteristics and siRNA activity of self assembled polyplexes formed with chol-siRNA or unmodified siRNA were compared using three types of conventional, positively charged polymers: (i) biodegradable, cross-linked nanogels (BDNG) (ii) graft copolymers (PEI-PEG), and (iii) linear block copolymers (PLL10-PEG, and PLL50-PEG). Chol-siRNA did not alter complex formation or the resistance of polyplexes to siRNA displacement by heparin but increased nuclease protection by BDNG, PLL10-PEG, and PLL50-PEG polyplexes over polyplexes with unmodified siRNA. Chol-CYPB siRNA increased suppression of native CYPB mRNA in mammary microvascular endothelial cells (MVEC) by BDNG polyplexes (35%) and PLL10-PEG polyplexes (69%) over comparable CYPB siRNA polyplexes but had no effect on PEI-PEG or PLL50-PEG polyplexes. Overall, these results indicate that complexation of chol-siRNA increases nuclease protection and mRNA suppression by select siRNA polyplexes. These results also suggest that polycationic block length is an important factor in increasing mRNA suppression by PLL-PEG chol-siRNA polyplexes in mammary MVEC. Copyright © 2010 Elsevier Ltd. All rights reserved.

Simultaneous Detection of Dopamine and Uric Acid Using a Poly(l-lysine)/Graphene Oxide Modified Electrode

PubMed Central

Zhang, Yuehua; Lei, Wu; Xu, Yujuan; Xia, Xifeng; Hao, Qingli

2016-01-01

A novel, simple and selective electrochemical method was investigated for the simultaneous detection of dopamine (DA) and uric acid (UA) on a poly(l-lysine)/graphene oxide (GO) modified glassy carbon electrode (PLL/GO/GCE) by differential pulse voltammetry (DPV). The electrochemically prepared PLL/GO sensory platform toward the oxidation of UA and DA exhibited several advantages, including high effective surface area, more active sites and enhanced electrochemical activity. Compared to the PLL-modified GCE (PLL/GCE), GO-modified GCE and bare GCE, the PLL/GO/GCE exhibited an increase in the anodic potential difference and a remarkable enhancement in the current responses for both UA and DA. For the simultaneous detection of DA and UA, the detection limits of 0.021 and 0.074 μM were obtained, while 0.031 and 0.018 μM were obtained as the detection limits for the selective detection of UA and DA, using DPV in the linear concentration ranges of 0.5 to 20.0 and 0.5 to 35 μM, respectively. In addition, the PLL/GO/GCE demonstrated good reproducibility, long-term stability, excellent selectivity and negligible interference of ascorbic acid (AA). The proposed modified electrode was successfully implemented in the simultaneous detection of DA and UA in human blood serum, urine and dopamine hydrochloride injection with satisfactory results. PMID:28335305

Preparation of poly-L-lysine functionalized magnetic nanoparticles and their influence on viability of cancer cells

NASA Astrophysics Data System (ADS)

Khmara, I.; Koneracka, M.; Kubovcikova, M.; Zavisova, V.; Antal, I.; Csach, K.; Kopcansky, P.; Vidlickova, I.; Csaderova, L.; Pastorekova, S.; Zatovicova, M.

2017-04-01

This study was aimed at development of biocompatible amino-functionalized magnetic nanoparticles as carriers of specific antibodies able to detect and/or target cancer cells. Poly-L-lysine (PLL)-modified magnetic nanoparticle samples with different PLL/Fe3O4 content were prepared and tested to define the optimal PLL/Fe3O4 weight ratio. The samples were characterized for particle size and morphology (SEM, TEM and DLS), and surface properties (zeta potential measurements). The optimal PLL/Fe3O4 weight ratio of 1.0 based on both zeta potential and DLS measurements was in agreement with the UV/VIS measurements. Magnetic nanoparticles with the optimal PLL content were conjugated with antibody specific for the cancer biomarker carbonic anhydrase IX (CA IX), which is induced by hypoxia, a physiologic stress present in solid tumors and linked with aggressive tumor behavior. CA IX is localized on the cell surface with the antibody-binding epitope facing the extracellular space and is therefore suitable for antibody-based targeting of tumor cells. Here we showed that PLL/Fe3O4 magnetic nanoparticles exhibit cytotoxic activities in a cell type-dependent manner and bind to cells expressing CA IX when conjugated with the CA IX-specific antibody. These data support further investigations of the CA IX antibody-conjugated, magnetic field-guided/activated nanoparticles as tools in anticancer strategies.

A distinct role of pectate lyases in the formation of feeding structures induced by cyst and root-knot nematodes.

PubMed

Wieczorek, K; Elashry, A; Quentin, M; Grundler, F M W; Favery, B; Seifert, G J; Bohlmann, H

2014-09-01

Pectin in the primary plant cell wall is thought to be responsible for its porosity, charge density, and microfibril spacing and is the main component of the middle lamella. Plant-parasitic nematodes secrete cell wall-degrading enzymes that macerate the plant tissue, facilitating the penetration and migration within the roots. In sedentary endoparasitic nematodes, these enzymes are released only during the migration of infective juveniles through the root. Later, nematodes manipulate the expression of host plant genes, including various cell wall enzymes, in order to induce specific feeding sites. In this study, we investigated expression of two Arabidopsis pectate lyase-like genes (PLL), PLL18 (At3g27400) and PLL19 (At4g24780), together with pectic epitopes with different degrees of methylesterification in both syncytia induced by the cyst nematode Heterodera schachtii and giant cells induced by the root-knot nematode Meloidogyne incognita. We confirmed upregulation of PLL18 and PLL19 in both types of feeding sites with quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) and in situ RT-PCR. Furthermore, the functional analysis of mutants demonstrated the important role of both PLL genes in the development and maintenance of syncytia but not giant cells. Our results show that both enzymes play distinct roles in different infected root tissues as well as during parasitism of different nematodes.

Identification of a novel subgroup 16SrII-U phytoplasma associated with papaya little leaf disease.

PubMed

Yang, Yi; Jiang, Lei; Che, Haiyan; Cao, Xueren; Luo, Daquan

2016-09-01

Papaya is an important fruit crop cultivated in tropical and subtropical regions. Papaya little leaf (PLL) disease was observed in China. The phytoplasma 16S rRNA gene was detected from symptomatic papaya trees via PCR using phytoplasma universal primers P1/P7 followed by R16F2n/R16R2. No amplification products were obtained from templates of asymptomatic papaya trees. These results indicated a direct association between phytoplasma infection and PLL disease. Comparative and phylogenetic analyses of 16S rRNA gene sequences indicated that the papaya-infecting phytoplasmas under study belonged to the peanut witches' broom phytoplasma group (16SrII). Genotyping through use of computer-simulated RFLP analysis of 16S rRNA genes and coefficients of RFLP pattern similarities (0.97) reveal that the PLL phytoplasma was placed in a new subgroup. In this article, we describe the molecular characterization of a new phytoplasma associated with PLL disease and propose that the PLL phytoplasma be considered as a novel subgroup, 16SrII-U.

[The clinical effect and disquisition of anterior cervical approach surgery with posterior longitudinal ligament hook pliers and posterior longitudinal ligament nip pliers].

PubMed

Kuang, Ling-hao; Xu, Dong; Sun, Ya-wei; Cong, Jie; Tian, Ji-wei; Wang, Lei

2010-09-21

To study the clinical effect of anterior cervical approach surgery to removal posterior longitudinal ligament (PLL) with posterior longitudinal ligament hook pliers and posterior longitudinal ligament nip pliers. To retrospectively analyzed anterior cervical approach surgery treatment 73 patients who were cervical spondylosis myelopathy. All patients removal PLL with self-make instrument, According to JOA grade to evaluate effect of operations. Full patients removal PLL were in succeed, in shape of extradural has renew, the JOA grade were increase, (12.8 ± 3.2) vs (8.3 ± 1.9). Removal PLL were increase effect of downright decompress in anterior cervical approach surgery, Operations become safety agile and reduce the complications with self-make instrument.

The Integration of Family and Group Therapy as an Alternative to Juvenile Incarceration: A Quasi-Experimental Evaluation Using Parenting with Love and Limits.

PubMed

Karam, Eli A; Sterrett, Emma M; Kiaer, Lynn

2017-06-01

The current study employed a quasi-experimental design using both intent-to-treat and protocol adherence analysis of 155 moderate- to high-risk juvenile offenders to evaluate the effectiveness of Parenting with Love and Limits® (PLL), an integrative group and family therapy approach. Youth completing PLL had significantly lower rates of recidivism than the comparison group. Parents also reported statistically significant improvements in youth behavior. Lengths of service were also significantly shorter for the treatment sample than the matched comparison group by an average of 4 months. This study contributes to the literature by suggesting that intensive community-based combined family and group treatment is effective in curbing recidivism among high-risk juveniles. © 2015 Family Process Institute.

Noise in NC-AFM measurements with significant tip–sample interaction

PubMed Central

Lübbe, Jannis; Temmen, Matthias

2016-01-01

The frequency shift noise in non-contact atomic force microscopy (NC-AFM) imaging and spectroscopy consists of thermal noise and detection system noise with an additional contribution from amplitude noise if there are significant tip–sample interactions. The total noise power spectral density D Δ f(f m) is, however, not just the sum of these noise contributions. Instead its magnitude and spectral characteristics are determined by the strongly non-linear tip–sample interaction, by the coupling between the amplitude and tip–sample distance control loops of the NC-AFM system as well as by the characteristics of the phase locked loop (PLL) detector used for frequency demodulation. Here, we measure D Δ f(f m) for various NC-AFM parameter settings representing realistic measurement conditions and compare experimental data to simulations based on a model of the NC-AFM system that includes the tip–sample interaction. The good agreement between predicted and measured noise spectra confirms that the model covers the relevant noise contributions and interactions. Results yield a general understanding of noise generation and propagation in the NC-AFM and provide a quantitative prediction of noise for given experimental parameters. We derive strategies for noise-optimised imaging and spectroscopy and outline a full optimisation procedure for the instrumentation and control loops. PMID:28144538

Performance Improvement of Receivers Based on Ultra-Tight Integration in GNSS-Challenged Environments

PubMed Central

Qin, Feng; Zhan, Xingqun; Du, Gang

2013-01-01

Ultra-tight integration was first proposed by Abbott in 2003 with the purpose of integrating a global navigation satellite system (GNSS) and an inertial navigation system (INS). This technology can improve the tracking performances of a receiver by reconfiguring the tracking loops in GNSS-challenged environments. In this paper, the models of all error sources known to date in the phase lock loops (PLLs) of a standard receiver and an ultra-tightly integrated GNSS/INS receiver are built, respectively. Based on these models, the tracking performances of the two receivers are compared to verify the improvement due to the ultra-tight integration. Meanwhile, the PLL error distributions of the two receivers are also depicted to analyze the error changes of the tracking loops. These results show that the tracking error is significantly reduced in the ultra-tightly integrated GNSS/INS receiver since the receiver's dynamics are estimated and compensated by an INS. Moreover, the mathematical relationship between the tracking performances of the ultra-tightly integrated GNSS/INS receiver and the quality of the selected inertial measurement unit (IMU) is derived from the error models and proved by the error comparisons of four ultra-tightly integrated GNSS/INS receivers aided by different grade IMUs.

Noise in NC-AFM measurements with significant tip-sample interaction.

PubMed

Lübbe, Jannis; Temmen, Matthias; Rahe, Philipp; Reichling, Michael

2016-01-01

The frequency shift noise in non-contact atomic force microscopy (NC-AFM) imaging and spectroscopy consists of thermal noise and detection system noise with an additional contribution from amplitude noise if there are significant tip-sample interactions. The total noise power spectral density D Δ f ( f m ) is, however, not just the sum of these noise contributions. Instead its magnitude and spectral characteristics are determined by the strongly non-linear tip-sample interaction, by the coupling between the amplitude and tip-sample distance control loops of the NC-AFM system as well as by the characteristics of the phase locked loop (PLL) detector used for frequency demodulation. Here, we measure D Δ f ( f m ) for various NC-AFM parameter settings representing realistic measurement conditions and compare experimental data to simulations based on a model of the NC-AFM system that includes the tip-sample interaction. The good agreement between predicted and measured noise spectra confirms that the model covers the relevant noise contributions and interactions. Results yield a general understanding of noise generation and propagation in the NC-AFM and provide a quantitative prediction of noise for given experimental parameters. We derive strategies for noise-optimised imaging and spectroscopy and outline a full optimisation procedure for the instrumentation and control loops.

Gene Silencing by Gold Nanoshell-Mediated Delivery and Laser-Triggered Release of Antisense Oligonucleotide and siRNA

PubMed Central

Huschka, Ryan; Barhoumi, Aoune; Liu, Qing; Roth, Jack A.; Ji, Lin; Halas, Naomi J.

2013-01-01

The approach of RNA interference (RNAi)- using antisense DNA or RNA oligonucleotides to silence activity of a specific pathogenic gene transcript and reduce expression of the encoded protein- is very useful in dissecting genetic function and holds significant promise as a molecular therapeutic. A major obstacle in achieving gene silencing with RNAi technology is the systemic delivery of therapeutic oligonucleotides. Here we demonstrate an engineered gold nanoshell (NS)-based therapeutic oligonucleotide delivery vehicle, designed to release its cargo on demand upon illumination with a near-infrared (NIR) laser. A poly(L)lysine peptide (PLL) epilayer covalently attached to the NS surface (NS-PLL) is used to capture intact, single-stranded antisense DNA oligonucleotides, or alternatively, double-stranded short-interfering RNA (siRNA) molecules. Controlled release of the captured therapeutic oligonucleotides in each case is accomplished by continuous wave NIR laser irradiation at 800 nm, near the resonance wavelength of the nanoshell. Fluorescently tagged oligonucleotides were used to monitor the time-dependent release process and light-triggered endosomal release. A green fluorescent protein (GFP)-expressing human lung cancer H1299 cell line was used to determine cellular uptake and gene silencing mediated by the NS-PLL carrying GFP gene-specific single-stranded DNA antisense oligonucleotide (AON-GFP), or a double-stranded siRNA (siRNA-GFP), in vitro. Light-triggered delivery resulted in ∼ 47% and ∼49% downregulation of the targeted GFP expression by AON-GFP and siRNA-GFP, respectively. Cytotoxicity induced by both the NS-PLL delivery vector and by laser irradiation is minimal, as demonstrated by a XTT cell proliferation assay. PMID:22862291

Robust GPS carrier tracking under ionospheric scintillation

NASA Astrophysics Data System (ADS)

Susi, M.; Andreotti, M.; Aquino, M. H.; Dodson, A.

2013-12-01

Small scale irregularities present in the ionosphere can induce fast and unpredictable fluctuations of Radio Frequency (RF) signal phase and amplitude. This phenomenon, known as scintillation, can degrade the performance of a GPS receiver leading to cycle slips, increasing the tracking error and also producing a complete loss of lock. In the most severe scenarios, if the tracking of multiple satellites links is prevented, outages in the GPS service can also occur. In order to render a GPS receiver more robust under scintillation, particular attention should be dedicated to the design of the carrier tracking stage, that is the receiver's part most sensitive to these types of phenomenon. This paper exploits the reconfigurability and flexibility of a GPS software receiver to develop a tracking algorithm that is more robust under ionospheric scintillation. For this purpose, first of all, the scintillation level is monitored in real time. Indeed the carrier phase and the post correlation terms obtained by the PLL (Phase Locked Loop) are used to estimate phi60 and S4 [1], the scintillation indices traditionally used to quantify the level of phase and amplitude scintillations, as well as p and T, the spectral parameters of the fluctuations PSD. The effectiveness of the scintillation parameter computation is confirmed by comparing the values obtained by the software receiver and the ones provided by a commercial scintillation monitoring, i.e. the Septentrio PolarxS receiver [2]. Then the above scintillation parameters and the signal carrier to noise density are exploited to tune the carrier tracking algorithm. In case of very weak signals the FLL (Frequency Locked Loop) scheme is selected in order to maintain the signal lock. Otherwise an adaptive bandwidth Phase Locked Loop (PLL) scheme is adopted. The optimum bandwidth for the specific scintillation scenario is evaluated in real time by exploiting the Conker formula [1] for the tracking jitter estimation. The performance of the proposed tracking scheme is assessed by using both simulated and real data. Real data have been collected in Vietnam by using a USRP (Universal Software Radio Peripheral) N210 front end connected to a rubidium oscillator. Selected events are exploited in order to challenge the algorithm with strong phase and amplitude variations. Moreover, simulated data have been collected by using the prototype of a digital front end developed by Novatel, namely the 'Firehose'. Since the latter includes a TCXO oscillator, the proposed tracking scheme is also opportunely modified to take in account the clock error contribution. References 1. R.S., Conker, M. B. El-Arini, C. J. Hegarty, and T. Hsiao, Modelling the effects of ionospheric scintillation on GPS/satellite-based augmentation system availability. Radio Sci., 38, 1, 1001, doi: 10.1029/2000RS002604, 2003. 2. B. Bougard et al, 'CIGALA: Challenging the Solar Maximum in Brazil with PolaRxS,' ION GNSS, Portland, Sept. 2011.

Grid Integrated Type 3 Wind Systems - Modeling, and Line Protection Performance Analysis using the RTDS

NASA Astrophysics Data System (ADS)

Jain, Rishabh

In this thesis, the line protection elements and their supervisory elements are analyzed in context of Type 3 (Doubly Fed Induction Generator based) grid integrated wind turbine systems. The underlying converter and controller design algorithms and topologies are discussed. A detailed controller for the Type 3 wind turbine system is designed and integrated to the grid using the RTDS. An alternative to the conventional PLL for tracking of rotor frequency is designed and implemented. A comparative analysis of the performance of an averaged model and the corresponding switching model is presented. After completing the WT model design, the averaged model is used to model an aggregate 10-generator equivalent model tied to a 230kV grid via a 22kV collector. This model is a great asset to understand dynamics, and the unfaulted and faulted behavior of aggregated and single-turbine Type 3 WT systems. The model is then utilized to analyze the response of conventional protection schemes (Line current Differential and Mho Distance elements) and their respective supervisory elements of modern commercial protection relays in real time by hardware-in-the-loop simulation using the RTDS. Differences in the behavior of these elements compared to conventional power systems is noted. Fault are analyzed from the relay's perspective and the reasons for the observed behavior are presented. Challenges associated with sequence components and relay sensitivity are discussed and alternate practices to circumvent these issues are recommended.

Thermal inactivation kinetics of Lactococcus lactis subsp. lactis bacteriophage pll98-22.

PubMed

Sanlibaba, Pinar; Buzrul, S; Akkoç, Nefise; Alpas, H; Akçelik, M

2009-03-01

Survival curves of Lactococcus lactis subsp. lactis bacteriophage pll98 inactivated by heat were obtained at seven temperature values (50-80 degrees C) in M17 broth and skim milk. Deviations from first-order kinetics in both media were observed as sigmoidal shapes in the survival curves of pll98. An empirical model with four parameters was used to define the thermal inactivation. Number of parameters of the model was reduced from four to two in order to increase the robustness of the model. The reduced model produced comparable fits to the full model. Both the survival data and the calculations done using the reduced model (time necessary to reduce the number of phage pll98 six- or seven- log10) indicated that skim milk is a more protective medium than M17 broth within the assayed temperature range.

CMOS Optoelectronic Lock-In Amplifier With Integrated Phototransistor Array.

PubMed

An Hu; Chodavarapu, Vamsy P

2010-10-01

We describe the design and development of an optoelectronic lock-in amplifier (LIA) for optical sensing and spectroscopy applications. The prototype amplifier is fabricated using Taiwan Semiconductor Manufacturing Co. complementary metal-oxide semiconductor 0.35-μm technology and uses a phototransistor array (total active area is 400 μm × 640μm) to convert the incident optical signals into electrical currents. The photocurrents are then converted into voltage signals using a transimpedance amplifier for subsequent convenient signal processing by the LIA circuitry. The LIA is optimized to be operational at 20-kHz modulation frequency but is operational in the frequency range from 13 kHz to 25 kHz. The system is tested with a light-emitting diode (LED) as the light source. The noise and signal distortions are suppressed with filters and a phase-locked loop (PLL) implemented in the LIA. The output dc voltage of the LIA is proportional to the incident optical power. The minimum measured dynamic reserve and sensitivity are 1.31 dB and 34 mV/μW, respectively. The output versus input relationship has shown good linearity. The LIA consumes an average power of 12.79 mW with a 3.3-V dc power supply.

Asymmetric resonance frequency analysis of in-plane electrothermal silicon cantilevers for nanoparticle sensors

NASA Astrophysics Data System (ADS)

Bertke, Maik; Hamdana, Gerry; Wu, Wenze; Marks, Markus; Suryo Wasisto, Hutomo; Peiner, Erwin

2016-10-01

The asymmetric resonance frequency analysis of silicon cantilevers for a low-cost wearable airborne nanoparticle detector (Cantor) is described in this paper. The cantilevers, which are operated in the fundamental in-plane resonance mode, are used as a mass-sensitive microbalance. They are manufactured out of bulk silicon, containing a full piezoresistive Wheatstone bridge and an integrated thermal heater for reading the measurement output signal and stimulating the in-plane excitation, respectively. To optimize the sensor performance, cantilevers with different cantilever geometries are designed, fabricated and characterized. Besides the resonance frequency, the quality factor (Q) of the resonance curve has a high influence concerning the sensor sensitivity. Because of an asymmetric resonance behaviour, a novel fitting function and method to extract the Q is created, different from that of the simple harmonic oscillator (SHO). For testing the sensor in a long-term frequency analysis, a phase- locked loop (PLL) circuit is employed, yielding a frequency stability of up to 0.753 Hz at an Allan variance of 3.77 × 10-6. This proposed asymmetric resonance frequency analysis method is expected to be further used in the process development of the next-generation Cantor.

Enantiomeric separations of chiral pharmaceuticals using chirally modified tetrahexahedral Au nanoparticles

NASA Astrophysics Data System (ADS)

Shukla, N.; Yang, D.; Gellman, A. J.

2016-06-01

Tetrahexahedral (THH, 24-sided) Au nanoparticles modified with D- or L-cysteine (Cys) have been used as enantioselective separators of the chiral pharmaceutical propranolol (PLL) in solution phase. Polarimetry has been used to measure the rotation of linearly polarized light by solutions containing mixtures of PLL and Cys/THH-Au NPs with varying enantiomeric excesses of each. Polarimetry yields clear evidence of enantiospecific adsorption of PLL onto the Cys/THH-Au NPs. This extends prior work using propylene oxide as a test chiral probe, by using the crystalline THH Au NPs with well-defined facets to separate a real pharmaceutical. This work suggests that chiral nanoparticles, coupled with a density separation method such as centrifugation, could be used for enantiomeric purification of real pharmaceuticals. A simple robust model developed earlier has also been used to extract the enantiospecific equilibrium constants for R- and S-PLL adsorption onto the D- and L-Cys/THH-Au NPs.

Pharmacological and therapeutic properties of carrier bound methotrexate against tumor confined to a third space body compartment.

PubMed

Chu, B C; Howell, S B

1981-11-01

The pharmacokinetics and therapeutic effectiveness of methotrexate (MTX) and MTX covalently bound to bovine serum albumin (MTX-BSA) and poly-l-lysine, MW 3,000 (MTX-PLL 3K) or MW 40,000 to 60,000 (MTX-PLL 40-60K) were compared when these drugs were injected directly into the pleural cavities of BDF1 mice containing the L1210 tumor. Simultaneous measurements od drug levels in both pleural fluid and blood after a single dose demonstrated that free MTX and MTX-PLL 3K were cleared from the pleural cavity and blood within 4 hr, MTX-PLL 40K-60K was cleared within 2 hr, and MTX-BSA was still present in the tumor compartment at 48 hr. The coupling of MTX to these carriers increased its toxicity by extending the half-life of MTX-BSA within the animal and by incorporating a toxic PLL derivative as a carrier. At equitoxic doses, a single dose of MTX-BSA gave a peak increase in lifespan (ILS) of 50% (at 35 mg/kg) compared with a peak ILS of 30 to 35% for both free drug (at 95 mg/kg) and the MTX-PLL derivatives (at 1.4-6 mg/kg). Systemic administration of sufficient leucovorin to provide partial marrow protection compromised the antitumor activity of both MTX and MTX-BSA in the pleural cavity, and although leucovorin permitted higher doses to be used, this resulted in only a small increase in peak ILS for MTX-BSA on a single dose schedule.

First-in-human response of BCL-2 inhibitor venetoclax in T-cell prolymphocytic leukemia.

PubMed

Boidol, Bernd; Kornauth, Christoph; van der Kouwe, Emiel; Prutsch, Nicole; Kazianka, Lukas; Gültekin, Sinan; Hoermann, Gregor; Mayerhoefer, Marius E; Hopfinger, Georg; Hauswirth, Alexander; Panny, Michael; Aretin, Marie-Bernadette; Hilgarth, Bernadette; Sperr, Wolfgang R; Valent, Peter; Simonitsch-Klupp, Ingrid; Moriggl, Richard; Merkel, Olaf; Kenner, Lukas; Jäger, Ulrich; Kubicek, Stefan; Staber, Philipp B

2017-12-07

T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive T-lymphoid malignancy usually refractory to current treatment strategies and associated with short overall survival. By applying next-generation functional testing of primary patient-derived lymphoma cells using a library of 106 US Food and Drug Administration (FDA)-approved anticancer drugs or compounds currently in clinical development, we set out to identify novel effective treatments for T-PLL patients. We found that the B-cell lymphoma 2 (BCL-2) inhibitor venetoclax (ABT-199) demonstrated the strongest T-PLL-specific response when comparing individual ex vivo drug response in 86 patients with refractory hematologic malignancies. Mechanistically, responses to venetoclax correlated with protein expression of BCL-2 but not with expression of the BCL-2 family members myeloid cell leukemia 1 (MCL-1) and BCL-XL in lymphoma cells. BCL-2 expression was inversely correlated with the expression of MCL-1. Based on the ex vivo responses, venetoclax treatment was commenced in 2 late-stage refractory T-PLL patients resulting in clinical responses. Our findings demonstrate first evidence of single-agent activity of venetoclax both ex vivo and in humans, offering a novel agent in T-PLL. © 2017 by The American Society of Hematology.

Advances in the understanding and management of T-cell prolymphocytic leukemia

PubMed Central

Laribi, Kamel; Lemaire, Pierre; Sandrini, Jeremy; Baugier de Materre, Alix

2017-01-01

T-prolymphocytic leukemia (T-PLL) is a rare T-cell neoplasm with an aggressive clinical course. Leukemic T-cells exhibit a post-thymic T-cell phenotype (Tdt−, CD1a−, CD5+, CD2+ and CD7+) and are generally CD4+/CD8−, but CD4+/CD8+ or CD8+/CD4− T-PLL have also been reported. The hallmark of T-PLL is the rearrangement of chromosome 14 involving genes for the subunits of the T-cell receptor (TCR) complex, leading to overexpression of the proto-oncogene TCL1. In addition, molecular analysis shows that T-PLL exhibits substantial mutational activation of the IL2RG-JAK1-JAK3-, STAT5B axis. T-PLL patients have a poor prognosis, due to a poor response to conventional chemotherapy. Monoclonal antibody therapy with antiCD52-alemtuzumab has considerably improved outcomes, but the responses to treatment are transient; hence, patients who achieve a response to therapy are considered for stem cell transplantation (SCT). This combined approach has extended the median survival to four years or more. Nevertheless, new approaches using well-tolerated therapies that target growth and survival signals are needed for most patients unable to receive intensive chemotherapy. PMID:29262669

Imaging trypsin activity through changes in the orientation of liquid crystals coupled to the interactions between a polyelectrolyte and a phospholipid layer.

PubMed

Hu, Qiong-Zheng; Jang, Chang-Hyun

2012-03-01

In this study, we developed a new type of liquid crystal (LC)-based sensor for the real-time and label-free monitoring of enzymatic activity through changes in the orientation of LCs coupled to the interactions between polyelectrolyte and phospholipid. The LCs changed from dark to bright after an aqueous solution of poly-l-lysine (PLL) was transferred onto a self-assembled monolayer of the phospholipid, dioleoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt (DOPG), at the aqueous/LC interface. Interactions between the positively charged PLL and the negatively charged DOPG drove the reorganization of the phospholipid membrane, which induced an orientational transition in the LCs from a homeotropic to planar state. Since the serine endopeptidase trypsin can enzymatically catalyze the hydrolysis of PLL, the dark-to-bright shift in the optical response was not observed after transferring a mixed solution of PLL and trypsin onto the DOPG-decorated LC interface, indicating that no orientational transitions in the LCs occurred. However, the optical response from dark to bright was observed when the mixture in the optical cell was replaced by an aqueous solution of PLL. Control experiments with trypsin or an aqueous mixture of PLL and deactivated trypsin further confirmed the feasibility of this approach. The detection limit of trypsin was determined to be ~1 μg/mL. This approach holds great promise for use in the development of LC-based sensors for the detection of enzymatic reactions in cases where the biological polyelectrolyte substrates of enzymes could disrupt the organization of the membrane and induce orientational transitions of LCs at the aqueous/LC interface. © 2012 American Chemical Society

Electrochemical DNA biosensor for bovine papillomavirus detection using polymeric film on screen-printed electrode.

PubMed

Nascimento, Gustavo A; Souza, Elaine V M; Campos-Ferreira, Danielly S; Arruda, Mariana S; Castelletti, Carlos H M; Wanderley, Marcela S O; Ekert, Marek H F; Bruneska, Danyelly; Lima-Filho, José L

2012-01-01

A new electrochemical DNA biosensor for bovine papillomavirus (BPV) detection that was based on screen-printed electrodes was comprehensively studied by electrochemical methods of cyclic voltammetry (CV) and differential pulse voltammetry (DPV). A BPV probe was immobilised on a working electrode (gold) modified with a polymeric film of poly-L-lysine (PLL) and chitosan. The experimental design was carried out to evaluate the influence of polymers, probe concentration (BPV probe) and immobilisation time on the electrochemical reduction of methylene blue (MB). The polymer poly-L-lysine (PLL), a probe concentration of 1 μM and an immobilisation time of 60 min showed the best result for the BPV probe immobilisation. With the hybridisation of a complementary target sequence (BPV target), the electrochemical signal decreased compared to a BPV probe immobilised on the modified PLL-gold electrode. Viral DNA that was extracted from cattle with papillomatosis also showed a decrease in the MB electrochemical reduction, which suggested that the decreased electrochemical signal corresponded to a bovine papillomavirus infection. The hybridisation specificity experiments further indicated that the biosensor could discriminate the complementary sequence from the non-complementary sequence. Thus, the results showed that the development of analytical devices, such as a biosensor, could assist in the rapid and efficient detection of bovine papillomavirus DNA and help in the prevention and treatment of papillomatosis in cattle. Copyright © 2012 Elsevier B.V. All rights reserved.

Statewide Implementation of Parenting with Love and Limits Among Youth with Co-Existing Internalizing and Externalizing Functional Impairments Reduces Return to Service Rates and Treatment Costs.

PubMed

Sterrett-Hong, Emma M; Karam, Eli; Kiaer, Lynn

2017-09-01

Many community mental health (CMH) systems contain inefficiencies, contributing to unmet need for services among youth. Using a quasi-experimental research design, we examined the implementation of an adapted structural-strategic family intervention, Parenting with Love and Limits, in a state CMH system to increase efficiency of services to youth with co-existing internalizing and externalizing functional impairments (PLL n = 296; Treatment-As-Usual n = 296; 54% male; 81% Caucasian). Youth receiving PLL experienced shorter treatment durations and returned to CMH services at significantly lower rates than youth receiving treatment-as-usual. They also demonstrated significant decreases in internalizing and externalizing symptoms over time. Findings lay the foundation for further examination of the role of an adapted structural-strategic family treatment in increasing the efficiency of CMH systems.

Electrodeposited reduced graphene oxide incorporating polymerization of l-lysine on electrode surface and its application in simultaneous electrochemical determination of ascorbic acid, dopamine and uric acid.

PubMed

Zhang, Dongdong; Li, Lingzhi; Ma, Weina; Chen, Xia; Zhang, Yanmin

2017-01-01

This paper demonstrates a novel strategy for the construction of a graphene hybrid composites film, which was fabricated by electrodeposited reduced graphene oxide (ERGO) incorporating polymerization of l-lysine (PLL) onto glassy carbon electrode (GCE). Here we show that graphene films can be prepared on electrodes directly from GO dispersions by one-step electrodeposition technique based on electropolymerized PLL as a positively charged polymer interface to adsorb negatively charged GO nanosheets through electrostatic attraction. The thickness of graphene film can be easily controlled by using the electrodeposition technique, a distinct advantage over previously developed methods. The electrochemically reduced process of GO and electropolymerization of l-lysine were investigated by cyclic voltammetry with a wide potential range. The surface morphology of the modified electrode was characterized by scanning electron microscopy. The ERGO/PLL/GCE shows conducive to electron transfer kinetics for Fe(CN) 6 3- /Fe(CN) 6 4- redox probes, compared with bare GCE, PLL/GCE and ERGO/GCE. The electrochemical behaviors of ascorbic acid (AA), dopamine (DA) and uric acid (UA) at ERGO/PLL/GCE were investigated by cyclic voltammetry, and the results suggest that the modified electrode exhibits enhanced electrocatalytic activity toward these important molecules. Under physiological condition and in the co-existence system of AA, DA and UA, the ERGO/PLL/GCE showed linear voltammetric responses in the concentration of 100μM-1200μM for AA, 2.0μM-60μM for DA and 20μM-200μM for UA, and with the detection limits (S/N=3) of 2.0μM, 0.10μM and 0.15μM for AA, DA and UA, respectively. The developed method has been applied to simultaneous determination of AA, DA and UA in human urine with satisfactory recoveries of 104.2%, 95.4% and 99.9%, respectively. This work demonstrates that the attractive features of ERGO/PLL provide promising applications in simultaneous determination of AA, DA and UA in physiological and pathological studies. Copyright © 2016 Elsevier B.V. All rights reserved.

Protein adsorption and biomimetic mineralization behaviors of PLL-DNA multilayered films assembled onto titanium

NASA Astrophysics Data System (ADS)

Gao, Wenli; Feng, Bo; Ni, Yuxiang; Yang, Yongli; Lu, Xiong; Weng, Jie

2010-11-01

Titanium and its alloys are frequently used as surgical implants in load bearing situations, such as hip prostheses and dental implants, owing to their biocompatibility, mechanical and physical properties. In this paper, a layer-by-layer (LBL) self-assembly technique, based on the polyelectrolyte-mediated electrostatic adsorption of poly-L-lysine (PLL) and DNA, was used to the formation of multilayer on titanium surfaces. Then bovine serum albumin (BSA) adsorption and biomimetic mineralization of modified surfaces were studied. The chemical composition and wettability of assembled substrates were investigated by X-ray photoelectron spectroscopy (XPS), fluorescence microscopy and water contact angle measurement, respectively. The XPS analysis indicated that the layers were assembled successfully through electrostatic attractions. The measurement with ultraviolet (UV) spectrophotometer revealed that the LBL films enhanced ability of BSA adsorption onto titanium. The adsorption quantity of BSA on the surface terminated with PLL was higher than that of the surface terminated with DNA, and the samples of TiOH/P/D/P absorbed BSA most. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) showed that samples of assembled PLL or/and DNA had better bioactivity in inducing HA formation. Thus the assembling of PLL and DNA onto the surface of titanium in turn via a layer-by-layer self-assembly technology can improve the bioactivity of titanium.

AOTF-based near-infrared imaging spectrometer for rapid identification of camouflaged target

NASA Astrophysics Data System (ADS)

Gao, Zhifan; Zeng, Libo; Wu, Qiongshui

2014-11-01

Acousto-optic tunable filter (AOTF) is a novel device for spectrometer. The electronic tunability qualifies it with the most compelling advantages of higher wavelength scan rate over the conventional spectrometers that are mechanically tuned, and the feature of large angular aperture makes the AOTF particularly suitable in imaging applications. In this research, an AOTF-based near-infrared imaging spectrometer was developed. The spectrometer consists of a TeO2 AOTF module, a near-infrared imaging lens assembly, an AOTF controller, an InGaAs array detector, an image acquisition card, and a PC. A precisely designed optical wedge is placed at the emergent surface of the AOTF to deal with the inherent dispersion of the TeO2 that may degrade the spatial resolution. The direct digital synthesizer (DDS) techniques and the phase locked loop (PLL) techniques are combined for radio frequency (RF) signal synthesis. The PLL is driven by the DDS to take advantage of both their merits of high frequency resolution, high frequency scan rate and strong spurious signals resistance capability. All the functions relating to wavelength scan, image acquisition, processing, storge and display are controlled by the PC. Calibration results indicate that the spectral range is 898~1670 nm, the spectral resolution is 6.8 nm(@1064 nm), the wavelength separation between frames in the spectral image assembly is 1.0 nm, and the processing time of a single image is less than 1 ms if a TV camera with 640×512 detector is incorporated. A prototype device was assembled to test the capability of differentiating samples with similar appearances, and satisfactory results were achieved. By this device, the chemical compositions and the distribution information can be obtained simultaneously. This system has the most advantages of no moving parts, fast wavelength scan and strong vibration resistance. The proposed imaging spectrometer has a significant application prospect in the area of identification of camouflaged target from complex backgrounds. In addition, only the objective lens and its accessories are required to be replaced for its use in microscopic spectral imaging system, which may be popularized to a large number of other possible applications.

Preparation, characterization and in vitro evaluation of ε-polylysine-loaded polymer blend microparticles for potential pancreatic cancer therapy.

PubMed

Chevalier, Merari T; García, Mónica C; Gonzalez, Daniela; Gomes-Filho, Sandro M; Bassères, Daniela S; Farina, Hernan; Alvarez, Vera A

2017-09-01

Peptide active ingredients show great promise regarding the treatment of various health-endangering diseases. It is reported that L-lysine inhibits the proliferation of several tumour lines in vitro and in vivo. However, proteins and peptide drugs possess certain disadvantages such as in vivo instability and short biological half-life. On the grounds that drug delivery systems can overcome a wide spectrum of bioactive compounds issues, a biopolymeric blend-based microparticulated system capable of delivering ε-polylysine (PLL) was developed. PLL-loaded poly((L)Lactic acid)/poly(D,L-Lactide)-co-poly(ethylene glycol)-based microparticles (PLL-PB-MPs) were prepared and fully characterised exhibiting a narrow size distribution (1.2 ± 0.12 µm), high loading efficiency (81%) and improved thermal stability (T d from 250 °C to 291 °C). The cytotoxicity and antiproliferative effect of PLL-PB-MPs in pancreatic adenocarcinoma cell lines BxPC3 and MIA PaCa-2 were confirmed. Due to their physicochemical and biopharmaceutical properties, PB-MPs constitute a promising carrier to deliver bioactive peptides.

Characterization and cell behavior of titanium surfaces with PLL/DNA modification via a layer-by-layer technique.

PubMed

Gao, Wenli; Feng, Bo; Lu, Xiong; Wang, Jianxin; Qu, Shuxin; Weng, Jie

2012-08-01

This study describes the fabrication of two types of multilayered films onto titanium by layer-by-layer (LBL) self-assembly, using poly-L-lysine (PLL) as the cationic polyelectrolyte and deoxyribonucleic acid (DNA) as the anionic polyelectrolyte. The assembling process of each component was studied using atomic force microscopy (AFM) and quartz crystal balance (QCM). Zeta potential of the LBL-coated microparticles was measured by dynamic light scattering. Titanium substrates with or without multilayered films were used in osteoblast cell culture experiments to study cell proliferation, viability, differentiation, and morphology. Results of AFM and QCM indicated the progressive build-up of the multilayered coatings. The surface morphology of three types of multilayered films showed elevations in the nanoscale range. The data of zeta potential showed that the surface terminated with PLL displayed positive charge while the surface terminated with DNA displayed negative charge. The proliferation of osteoblasts on modified titanium films was found to be greater than that on control (p < 0.05) after 3 and 7 days culture, respectively. Alamar blue measurement showed that the PLL/DNA-modified films have higher cell viability (p < 0.05) than the control. Still, the alkaline phosphatase activity assay revealed a better differentiated phenotype on three types of multilayered surfaces compared to noncoated controls. Collectively our results suggest that PLL/DNA were successfully used to surface engineer titanium via LBL technique, and enhanced its cell biocompatibility. Copyright © 2012 Wiley Periodicals, Inc.

Biodegradable Nanoparticles of mPEG-PLGA-PLL Triblock Copolymers as Novel Non-Viral Vectors for Improving siRNA Delivery and Gene Silencing

PubMed Central

Du, Jing; Sun, Ying; Shi, Qiu-Sheng; Liu, Pei-Feng; Zhu, Ming-Jie; Wang, Chun-Hui; Du, Lian-Fang; Duan, You-Rong

2012-01-01

Degradation of mRNA by RNA interference is one of the most powerful and specific mechanisms for gene silencing. However, insufficient cellular uptake and poor stability have limited its usefulness. Here, we report efficient delivery of siRNA via the use of biodegradable nanoparticles (NPs) made from monomethoxypoly(ethylene glycol)-poly(lactic-co-glycolic acid)-poly-l-lysine (mPEG-PLGA-PLL) triblock copolymers. Various physicochemical properties of mPEG-PLGA-PLL NPs, including morphology, size, surface charge, siRNA encapsulation efficiency, and in vitro release profile of siRNA from NPs, were characterized by scanning electron microscope, particle size and zeta potential analyzer, and high performance liquid chromatography. The levels of siRNA uptake and targeted gene inhibition were detected in human lung cancer SPC-A1-GFP cells stably expressing green fluorescent protein. Examination of the cultured SPC-A1-GFP cells with fluorescent microscope and flow cytometry showed NPs loading Cy3-labeled siRNA had much higher intracellular siRNA delivery efficiencies than siRNA alone and Lipofectamine-siRNA complexes. The gene silencing efficiency of mPEG-PLGA-PLL NPs was higher than that of commercially available transfecting agent Lipofectamine while showing no cytotoxicity. Thus, the current study demonstrates that biodegradable NPs of mPEG-PLGA-PLL triblock copolymers can be potentially applied as novel non-viral vectors for improving siRNA delivery and gene silencing. PMID:22312268

Inducement of a spontaneously wrinkled polydimethylsiloxane surface and its potential as a cell culture substrate.

PubMed

Kim, Da Som; Lee, Ho Won; Lee, Jong Hyun; Kwon, Hyuck Gi; Lee, Sang Wook; Han, Seung Jin; Jeong, Ok Chan

2018-06-18

Spontaneous wrinkling of a polydimethylsiloxane (PDMS) surface was induced by repeated thermal shrinkage of liquid PDMS coated onto a cured PDMS layer. We investigated and evaluated the potential of the resulting surface as a cell culture substrate by monitoring the viability, spreading area, and proliferation rate of MG-63 cells cultured on native, wrinkled, and poly-L-lysine (PLL)-coated PDMS surfaces. Cells seeded on the wrinkled and PLL-coated PDMS surfaces spread and adhered better than those on native surfaces. The numbers of attached cells growing on wrinkled and PLL-coated PDMS surfaces were higher than those of cells on a native PDMS surface. The spreading area of cells on the wrinkled surface was similar to that of cells on the PLL-coated surface, and was much larger than that on native PDMS. The proliferation rate of cells on the wrinkled surface was more than double that of cells on native PDMS. Reverse-transcription polymerase chain reaction (RT-PCR) analysis of integrin mRNA expression showed that cells on the wrinkled surface were more tightly attached due to higher expression of the protein than exhibited in cells on native PDMS. Thus, the novel findings of this study are that the induction of a wrinkled PDMS surface through a simple curing process produces a suitable cell culture substrate without need of surface modification, and that its effectiveness is comparable to that of a PLL-coated PDMS surface. Copyright © 2018 Elsevier B.V. All rights reserved.

Gadolinium-loaded polymeric nanoparticles modified with Anti-VEGF as multifunctional MRI contrast agents for the diagnosis of liver cancer.

PubMed

Liu, Yongjun; Chen, Zhijin; Liu, Chunxi; Yu, Dexin; Lu, Zaijun; Zhang, Na

2011-08-01

Molecular imaging is essential to increase the sensitivity and selectivity of cancer diagnosis especially in the early stage of tumor. Here, we designed a novel multifunctional polymeric nanoparticle contrast agent (Anti-VEGF PLA-PEG-PLL-Gd NP) simultaneously modified with Gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) and anti-vascular endothelial growth factor (VEGF) antibody to deliver Gd-DTPA to the tumor area and achieve the early diagnosis of hepatocellular carcinoma (HCC). The Anti-VEGF PLA-PEG-PLL-Gd NPs exhibited high T(1) relaxivity and no obvious cytotoxicity under the experimental concentrations in human hepatocellular carcinoma (HepG2) cells. The results of in vitro cell uptake experiments demonstrated that the uptake process of NPs was both concentration and time depended. Compared with non-targeted NPs, the Anti-VEGF antibody modified NPs showed much higher cell uptake in the HepG2 cells. During in vivo studies, the targeted NPs showed significantly signal intensity enhancement at the tumor site (mouse hepatocarcinoma tumor, H22) compared with non-targeted NPs and Gd-DTPA injection in tumor-bearing mice and the imaging time was significantly prolonged from less than an hour (Gd-DTPA injection group) to 12 h. These results demonstrated that this novel MRI contrast agent Anti-VEGF PLA-PEG-PLL-Gd NPs showed great potential in the early diagnosis of liver tumors. Copyright © 2011 Elsevier Ltd. All rights reserved.

In vivo modulation of foreign body response on polyurethane by surface entrapment technique.

PubMed

Khandwekar, Anand P; Patil, Deepak P; Hardikar, Anand A; Shouche, Yogesh S; Doble, Mukesh

2010-11-01

Implanted polymeric materials, such as medical devices, provoke the body to initiate an inflammatory reaction, known as the foreign body response (FBR), which causes several complications. In this study, polyurethane (Tecoflex®, PU) surface modified with the nonionic surfactant Tween80® (PU/T80) and the cell adhesive PLL-RGD peptide (PU/PLL-RGD) by a previously described entrapment technique were implanted in the peritoneal cavity of Wistar rats for 30 days. Implants were retrieved and examined for tissue reactivity and cellular adherence by various microscopic and analytical techniques. Surface-induced inflammatory response was assessed by real-time PCR based quantification of proinflammatory cytokine transcripts, namely, TNF-α and IL-1β, normalized to housekeeping gene GAPDH. Cellular adherence and their distribution profile were assessed by microscopic examination of H&E stained implant sections. It was observed that PU/PLL-RGD followed by the bare PU surface exhibited severe inflammatory and fibrotic response with an average mean thickness of 19 and 12 μm, respectively, in 30 days. In contrast, PU/T80 surface showed only a cellular monolayer of 2-3 μm in thickness, with a mild inflammatory response and no fibrotic encapsulation. The PU/PLL-RGD peptide-modified substrate promoted an enhanced rate of macrophage cell fusion to form foreign body giant cell (FBGCs), whereas FBGCs were rarely observed on Tween80®-modified substrate. The expression levels of proinflammatory cytokines (TNF-α and IL-1β) were upregulated on PU/PLL-RGD surface followed by bare PU, whereas the cytokine expressions were significantly suppressed on PU/T80 surface. Thus, our study highlights modulation of foreign body response on polyurethane surfaces through surface entrapment technique in the form of differential responses observed on PLL-RGD and Tween80® modified surfaces with the former effective in triggering tissue cell adhesion thereby fibrous encapsulation, while the later being mostly resistant to this phenomenon.

One-dimensional poly(L-lysine)-block-poly(L-threonine) assemblies exhibit potent anticancer activity by enhancing membranolysis.

PubMed

Chen, Yu-Fon; Shiau, Ai-Li; Chang, Sue-Joan; Fan, Nai-Shin; Wang, Chung-Teng; Wu, Chao-Liang; Jan, Jeng-Shiung

2017-06-01

Herein, we report the oncolytic activity of cationic, one-dimensional (1D) fibril assemblies formed from coil-sheet poly(L-lysine)-block-poly(L-threonine) (PLL-b-PLT) block copolypeptides for cancer therapy. The 1D fibril assemblies can efficiently interact with negatively charged cellular and mitochondrial membranes via electrostatic interactions, leading to necrosis via membrane lysis and apoptosis via the mitochondria-lytic effect. The concept is analogous to that of 1D drug carriers that exhibit enhanced cell penetration. In comparison to free PLL chains, PLL-b-PLT fibril assemblies exhibit selective cytotoxicity toward cancer cells, low hemolysis activity, enhanced membranolytic activity, and a different apoptosis pathway, which may be due to differences in the peptide-membrane interactions. Antitumor studies using a metastatic LL2 lung carcinoma model indicate that the fibril assemblies significantly inhibited tumor growth, improved survival in tumor-bearing mice and suppressed lung metastasis without obvious body weight loss. An additive efficacy was also observed for treatment with both PLL-b-PLT and cisplatin. These results support the feasibility of using 1D fibril assemblies as potential apoptotic anticancer therapeutics. We report that cationic, one-dimensional (1D) fibril assemblies formed by coil-sheet poly(L-lysine)-block-poly(L-threonine) (PLL-b-PLT) block copolypeptides exhibited potent anticancer activity by enhancing membranolysis. The 1D fibril assemblies can efficiently interact with negatively charged cellular and mitochondrial membranes via electrostatic interactions, leading to necrosis via membrane lysis and apoptosis via mitochondria-lytic effect. Moreover, the fibril assemblies exhibited low hemolytic activity and selective cytotoxicity toward cancer cell, which is advantageous as compared to PLL and most antimicrobial/anticancerous peptides. This study provides a new concept of using cationic, 1D fibril assemblies for cancer therapy. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Therapeutic supermolecular micelles of vitamin E succinate-grafted ε-polylysine as potential carriers for curcumin: Enhancing tumour penetration and improving therapeutic effect on glioma.

PubMed

Xu, He-Lin; Fan, Zi-Liang; ZhuGe, De-Li; Shen, Bi-Xin; Jin, Bing-Hui; Xiao, Jian; Lu, Cui-Tao; Zhao, Ying-Zheng

2017-10-01

Severe toxicity and poor tumour penetration are two intrinsic limited factors to hinder the broad clinical application for most of first-line chemotherapeutics. In this study, a novel vitamin E succinate-grafted ε-polylysine (VES-g-PLL) polymer was synthesized by using ε-polylysine as backbone. By adjusting VES graft ratio, VES-g-PLL (50) with a theoretic VES graft ratio of 50% could self-assemble into a supermolecular micelle with a hydrodynamic diameter (D h ) of ca.20nm, and Zeta potential of 19.6mV. VES-g-PLL micelles themselves displayed a strong anti-tumour effect on glioma. The poorly water-soluble curcumin was effectively encapsulated in VES-g-PLL micelles with the drug loading amount and entrapment efficiency reaching 4.32% and 82.27%, respectively. In a physiologic medium, curcumin-loaded VES-g-PLL micelles (Cur-Micelles) not only remained stable without obvious drug leakage but also sustained the release of its encapsulated curcumin for a long time. Because of the ultra-small size and positively-charged surface, Cur-Micelles penetrated the deeper tumour zone than free curcumin, resulting in a significant inhibition of tumour spheroids growth. Moreover, in vivo strong antitumor effect of Cur-Micelles was also exhibited at assistance of ultrasound-targeted microbubble destruction and the real-time MRI imaging demonstrated a nearly complete suppression of glioma after 28days of treatment. TUNEL staining showed that the therapeutic mechanism of Cur-Micelles was relevant to the apoptosis of tumour cells. Finally, in vivo nontoxicity of Cur-Micelles against normal organs including heart, liver, spleen, lung and kidney tissues was also demonstrated by the HE staining. In conclusion, VES-g-PLL micelles may serve as a potential carrier for curcumin to enhance tumour penetration and improve therapeutic effect on glioma. Copyright © 2017 Elsevier B.V. All rights reserved.

The effect of the triblock properties on the morphologies and photophysical properties of nanoparticle loaded with carboxylic dendrimer phthalocyanine

NASA Astrophysics Data System (ADS)

Lv, Huafei; Chen, Zhe; Yu, Xinxin; Pan, Sujuan; Zhang, Tiantian; Xie, Shusen; Yang, Hongqin; Peng, Yiru

2016-09-01

Photodynamic therapy (PDT) is an emerging alternative treatment for various cancers and age-related macular degeneration. Phthalocyanines (Pcs) and their substituted derivatives are under intensive investigation as the second generation photosensitizers. A big challenge for the application of Pcs is poor solubility and limited accumulation in the tumor tissues, which severely reduced its PDT efficacy. Nano-delivery systems such as polymeric micelles are promising tools for increasing the solubility and improving delivery efficiency of Pcs for PDT application. In this paper, nanoparticles of amphiphilic triblock copolymer poly(L-lysine)-b-poly (ethylene glycol)-b-poly(L-lysine) were developed to encapsulate 1-2 generation carboxylic poly (benzyl aryl ether) dendrimer. The morphologies and photophysical properties of polymeric nanoparticles loaded with 1-2 generation dendritic phthalocyanines (G1-ZnPc(COOH)8/m and G2-ZnPc(COOH)16/m) were studied by AFM, UV/Vis and fluorescent spectroscopic method. The morphologies of self-assembled PLL-PEG-PLL aggregates exhibited concentration dependence. Its morphologies changed from cocoon-like to spheral. The diameters of G1-ZnPc(COOH)8/m and G2-ZnPc(COOH)16/m were in the range of 33-147 nm, increasing with the increase of the concentration of PLL-PEG-PLL. The morphologies of G2-ZnPc(COOH)16/m also changed from cocoon-like to sphere with the increase of the concentration of PLL-PEG-PLL. It was found that, the no obviously Q change was observed between the free phthalocyanines and nanoparticles. The fluorescence intensity of polymer nanoparticles were higher enhanced compared with free dendritic phthalocyanines. The dendrimer phthalocyanine loaded with poly(L-lysine)-b-poly (ethylene glycol)-b-poly(L-lysine) presented suitable physical stability, improved photophysical properties suggesting it may be considered as a promising formulation for PDT.

Non-linear control of the output stage of a solar microinverter

NASA Astrophysics Data System (ADS)

Lopez-Santos, Oswaldo; Garcia, Germain; Martinez-Salamero, Luis; Avila-Martinez, Juan C.; Seguier, Lionel

2017-01-01

This paper presents a proposal to control the output stage of a two-stage solar microinverter to inject real power into the grid. The input stage of the microinverter is used to extract the maximum available power of a photovoltaic module enforcing a power source behavior in the DC-link to feed the output stage. The work here reported is devoted to control a grid-connected power source inverter with a high power quality level at the grid side ensuring the power balance of the microinverter regulating the voltage of the DC-link. The proposed control is composed of a sinusoidal current reference generator and a cascade type controller composed by a current tracking loop and a voltage regulation loop. The current reference is obtained using a synchronized generator based on phase locked loop (PLL) which gives the shape, the frequency and phase of the current signal. The amplitude of the reference is obtained from a simple controller regulating the DC-link voltage. The tracking of the current reference is accomplished by means of a first-order sliding mode control law. The solution takes advantage of the rapidity and inherent robustness of the sliding mode current controller allowing a robust behavior in the regulation of the DC-link using a simple linear controller. The analytical expression to determine the power quality indicators of the micro-inverter's output is theoretically solved giving expressions relating the converter parameters. The theoretical approach is validated using simulation and experimental results.

Monolayers of derivatized poly(l-lysine)-grafted poly(ethylene glycol) on metal oxides as a class of biomolecular interfaces

PubMed Central

Ruiz-Taylor, L. A.; Martin, T. L.; Zaugg, F. G.; Witte, K.; Indermuhle, P.; Nock, S.; Wagner, P.

2001-01-01

We report on the design and characterization of a class of biomolecular interfaces based on derivatized poly(l-lysine)-grafted poly(ethylene glycol) copolymers adsorbed on negatively charged surfaces. As a model system, we synthesized biotin-derivatized poly(l-lysine)-grafted poly(ethylene glycol) copolymers, PLL-g-[(PEGm)(1−x) (PEG-biotin)x], where x varies from 0 to 1. Monolayers were produced on titanium dioxide substrates and characterized by x-ray photoelectron spectroscopy. The specific biorecognition properties of these biotinylated surfaces were investigated with the use of radiolabeled streptavidin alone and within complex protein mixtures. The PLL-g-PEG-biotin monolayers specifically capture streptavidin, even from a complex protein mixture, while still preventing nonspecific adsorption of other proteins. This streptavidin layer can subsequently capture biotinylated proteins. Finally, with the use of microfluidic networks and protein arraying, we demonstrate the potential of this class of biomolecular interfaces for applications based on protein patterning. PMID:11158560

Sensorless control of ship propulsion interior permanent magnet synchronous motor based on a new sliding mode observer.

PubMed

Ren, Jun-Jie; Liu, Yan-Cheng; Wang, Ning; Liu, Si-Yuan

2015-01-01

This paper proposes a sensorless speed control strategy for ship propulsion interior permanent magnet synchronous motor (IPMSM) based on a new sliding-mode observer (SMO). In the SMO the low-pass filter and the method of arc-tangent calculation of extended electromotive force (EMF) or phase-locked loop (PLL) technique are not used. The calculation of the rotor speed is deduced from the Lyapunov function stability analysis. In order to reduce system chattering, sigmoid functions with switching gains being adaptively updated by fuzzy logic systems are innovatively incorporated into the SMO. Finally, simulation results for a 4.088 MW ship propulsion IPMSM and experimental results from a 7.5 kW IPMSM drive are provided to verify the effectiveness of the proposed SMO method. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

Encapsulation of curcumin in polyelectrolyte nanocapsules and their neuroprotective activity

NASA Astrophysics Data System (ADS)

Szczepanowicz, Krzysztof; Jantas, Danuta; Piotrowski, Marek; Staroń, Jakub; Leśkiewicz, Monika; Regulska, Magdalena; Lasoń, Władysław; Warszyński, Piotr

2016-09-01

Poor water solubility and low bioavailability of lipophilic drugs can be potentially improved with the use of delivery systems. In this study, encapsulation of nanoemulsion droplets was utilized to prepare curcumin nanocarriers. Nanosize droplets containing the drug were encapsulated in polyelectrolyte shells formed by the layer-by-layer (LbL) adsorption of biocompatible polyelectrolytes: poly-L-lysine (PLL) and poly-L-glutamic acid (PGA). The size of synthesized nanocapsules was around 100 nm. Their biocompatibility and neuroprotective effects were evaluated on the SH-SY5Y human neuroblastoma cell line using cell viability/toxicity assays (MTT reduction, LDH release). Statistically significant toxic effect was clearly observed for PLL coated nanocapsules (reduction in cell viability about 20%-60%), while nanocapsules with PLL/PGA coating did not evoke any detrimental effects on SH-SY5Y cells. Curcumin encapsulated in PLL/PGA showed similar neuroprotective activity against hydrogen peroxide (H2O2)-induced cell damage, as did 5 μM curcumin pre-dissolved in DMSO (about 16% of protection). Determination of concentration of curcumin in cell lysate confirmed that curcumin in nanocapsules has cell protective effect in lower concentrations (at least 20 times) than when given alone. Intracellular mechanisms of encapsulated curcumin-mediated protection engaged the prevention of the H2O2-induced decrease in mitochondrial membrane potential (MMP) but did not attenuate Reactive Oxygen Species (ROS) formation. The obtained results indicate the utility of PLL/PGA shell nanocapsules as a promising, alternative way of curcumin delivery for neuroprotective purposes with improved efficiency and reduced toxicity.

Encapsulation of curcumin in polyelectrolyte nanocapsules and their neuroprotective activity.

PubMed

Szczepanowicz, Krzysztof; Jantas, Danuta; Piotrowski, Marek; Staroń, Jakub; Leśkiewicz, Monika; Regulska, Magdalena; Lasoń, Władysław; Warszyński, Piotr

2016-09-02

Poor water solubility and low bioavailability of lipophilic drugs can be potentially improved with the use of delivery systems. In this study, encapsulation of nanoemulsion droplets was utilized to prepare curcumin nanocarriers. Nanosize droplets containing the drug were encapsulated in polyelectrolyte shells formed by the layer-by-layer (LbL) adsorption of biocompatible polyelectrolytes: poly-L-lysine (PLL) and poly-L-glutamic acid (PGA). The size of synthesized nanocapsules was around 100 nm. Their biocompatibility and neuroprotective effects were evaluated on the SH-SY5Y human neuroblastoma cell line using cell viability/toxicity assays (MTT reduction, LDH release). Statistically significant toxic effect was clearly observed for PLL coated nanocapsules (reduction in cell viability about 20%-60%), while nanocapsules with PLL/PGA coating did not evoke any detrimental effects on SH-SY5Y cells. Curcumin encapsulated in PLL/PGA showed similar neuroprotective activity against hydrogen peroxide (H2O2)-induced cell damage, as did 5 μM curcumin pre-dissolved in DMSO (about 16% of protection). Determination of concentration of curcumin in cell lysate confirmed that curcumin in nanocapsules has cell protective effect in lower concentrations (at least 20 times) than when given alone. Intracellular mechanisms of encapsulated curcumin-mediated protection engaged the prevention of the H2O2-induced decrease in mitochondrial membrane potential (MMP) but did not attenuate Reactive Oxygen Species (ROS) formation. The obtained results indicate the utility of PLL/PGA shell nanocapsules as a promising, alternative way of curcumin delivery for neuroprotective purposes with improved efficiency and reduced toxicity.

On-line capillary electrophoresis-based enzymatic methodology for the study of polymer-drug conjugates.

PubMed

Coussot, G; Ladner, Y; Bayart, C; Faye, C; Vigier, V; Perrin, C

2015-01-09

This work aims at studying the potentialities of an on-line capillary electrophoresis (CE)-based digestion methodology for evaluating polymer-drug conjugates degradability in the presence of free trypsin (in-solution digestion). A sandwich plugs injection scheme with transverse diffusion of laminar profile (TDLFP) mode was used to achieve on-line digestions. Electrophoretic separation conditions were established using poly-l-Lysine (PLL) as reference substrate. Comparison with off-line digestion was carried out to demonstrate the feasibility of the proposed methodology. The applicability of the on-line CE-based digestion methodology was evaluated for two PLL-drug conjugates and for the four first generations of dendrigraft of lysine (DGL). Different electrophoretic profiles presenting the formation of di, tri, and tetralysine were observed for PLL-drug and DGL. These findings are in good agreement with the nature of the linker used to link the drug to PLL structure and the predicted degradability of DGL. The present on-line methodology applicability was also successfully proven for protein conjugates hydrolysis. In summary, the described methodology provides a powerful tool for the rapid study of biodegradable polymers. Copyright © 2014 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brewer, Forrest; Incandela, Joseph

This project was slated to design and develop Rad-Hard IP components for 1Gb/s links and supporting hardware designs such as PLL, SER/DES, pad drivers and receivers and custom protocol hardware for the 1Gb/s channel. Also included in the proposal was a study of a hardened memory to be used as a packet buffer for channel and data concentrator components to meet the 1 Gb/s specification. Over the course of the proposal, technology change and innovation of hardware designs lead us away from the 1 Gb/s goal to contemplate much higher performance link IP which, we believed better met the goalsmore » of physics experiments. Note that CERN microelectronics had managed to create a 4.7 Gb/s link designed to drive optical fibers and containing infrastructure for connecting much lower bandwidth front-end devices. Our own work to that point had shown the possibility of constructing a link with much lower power, lower physical overhead but of equivalent performance that could be designed to integrate directly onto the front-end ASIC (ADC and data encoding) designs. Substantial overall power savings and experimental simplicity could be achieved by eliminating data transmission to data concentrators and data concentrators and related hardened buffering themselves, with conversion to optical media at a removed distance from the experiment core. We had already developed and tested Rad-Hard SER/DES components (1Gb in 130nm standard cells) and redundant Pad Drivers/Receivers (3+ Gb/s designed and measured performance), and had a viable 1Gb/s link design based on redundant a stuttered clock receiver and classical PLL, so the basic goals of the proposal had been achieved. Below, in chronological order, are the products and tools we constructed, as well as our tests and publications.« less

Poly-L-lysine/hydroxyapatite/carbon nanotube hybrid nanocomposite applied for piezoelectric immunoassay of carbohydrate antigen 19-9.

PubMed

Ding, Yanjun; Liu, Jia; Jin, Xiaoyong; Lu, Haixia; Shen, Guoli; Yu, Ruqin

2008-02-01

Hybrid composites are of special scientific interest for biochemical applications wherein the abilities to modulate the morphology and property of the hybrid material are important. In this paper, the formation of poly-L-lysine/hydroxyapatite/carbon nanotube (PLL/HA/CNT) hybrid nanoparticles is described and a general design strategy for an immunosensing platform has been proposed on the basis of PLL/HA/CNT nanocomposite adsorption of antibodies. Quartz crystal microbalance (QCM) used as a model transducer and the detection performances of the resulting immunosensor were investigated by use of the immuno-system of carbohydrate antigen 19-9 (CA19-9), an important indicator in the diagnosis of clinical cancers. The hybrid nanocomposite was characterized by the transmission electron microscope (TEM), scanning electron microscope (SEM) and Fourier transform-infrared (FT-IR) spectrum measurements. The frequency response characteristics for the processes of immobilization and immunoreaction of anchored anti-CA19-9 antibodies were studied in detail. It was found that the developed sensing interface has some advantages such as the activation-free immobilization and the high antigen-binding activities of antibodies. The as-prepared immunosensor can allow for the determination of CA19-9 in the concentration range of around 12.5-270.0 U ml(-1). Such an interface design with the hybrid nanocomposite should be tailored as a new alternative used for biosensor design.

Ebola Vaccination Using a DNA Vaccine Coated on PLGA-PLL/γPGA Nanoparticles Administered Using a Microneedle Patch.

PubMed

Yang, Hung-Wei; Ye, Ling; Guo, Xin Dong; Yang, Chinglai; Compans, Richard W; Prausnitz, Mark R

2017-01-01

Ebola DNA vaccine is incorporated into PLGA-PLL/γPGA nanoparticles and administered to skin using a microneedle (MN) patch. The nanoparticle delivery system increases vaccine thermostability and immunogenicity compared to free vaccine. Vaccination by MN patch produces stronger immune responses than intramuscular administration. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ratiometric biosensor array for multiplexed detection of microRNAs based on electrochemiluminescence coupled with cyclic voltammetry.

PubMed

Feng, Xiaobin; Gan, Ning; Zhang, Huairong; Li, Tianhua; Cao, Yuting; Hu, Futao; Jiang, Qianli

2016-01-15

A novel multiplexed ratiometric biosensor array was fabricated on a homemade screen-printed carbon electrode (SPCE) for near-simultaneous detection of microRNA (miRNA)-21 and miRNA-141 based on electrochemiluminescence (ECL) coupled with cyclic voltammetry (CV) method. In the detection system, the ECL signal tags (Ru-SiO2@PLL-Au) were fabricated using poly-l-lysine (PLL) as bridging agent and co-reactant to connect Ru-SiO2 (Ru(bpy)3(2+)-doped silica) and gold nanoparticles (Au NPs), which were respectively modified on two spatial resolved working electrodes (WE1 and WE2) of SPCE. Then the ferrocene (Fc)-labeled hairpin DNA (Fc-HDNA1 and Fc-HDNA2) as CV signal tags and ECL quenching material were immobilized on Ru-SiO2@PLL-Au. Upon miRNA-21 and miRNA-141 adding, the target miRNAs could hybridize with corresponding Fc-HDNA, which could lead to Fc away from Ru-SiO2@PLL-Au. Such conformational changes could recover the ECL of Ru-SiO2@PLL-Au and decreased the CV current of Fc, respectively. This "signal-on" of ECL and "signal-off" of CV were employed for dual-signal ratiometric readout. With the help of a multiplexed switch, two dual-signals from WE1 and WE2 were used for multiplexed detection of miRNA-21 and miRNA-141 down to 6.3 and 8.6fM, respectively. This approach was used in real sample analysis and has significant potential for miRNA biomarkers detection in a clinical laboratory setting. Copyright © 2015 Elsevier B.V. All rights reserved.

Facile preparation of well-defined AB2 Y-shaped miktoarm star polypeptide copolymer via the combination of ring-opening polymerization and click chemistry.

PubMed

Rao, Jingyi; Zhang, Yanfeng; Zhang, Jingyan; Liu, Shiyong

2008-10-01

Well-defined AB2 Y-shaped miktoarm star polypeptide copolymer, PZLL-b-(PBLG)2, was synthesized via a combination of ring-opening polymerization (ROP) of alpha-amino acid N-carboxyanhydride (NCA) and click chemistry, where PZLL is poly(epsilon-benzyloxycarbonyl-L-lysine) and PBLG is poly(gamma-benzyl-L-glutamate). First, two types of primary-amine-containing initiators, N-aminoethyl 3,5-bis(propargyloxyl)-benzamide and 3-azidopropylamine, were synthesized and employed for the ROP of NCA, leading to the formation of dialkynyl-terminated PZLL and azide-terminated PBLG, dialkynyl-PZLL and PBLG-N3, respectively. The subsequent copper(I)-catalyzed cycloaddition reaction between dialkynyl-PZLL and slightly excess PBLG-N3 led to facile preparation of PZLL-b-(PBLG)2 Y-shaped miktoarm star polypeptide copolymer. The excess PBLG-N3 was scavenged off by reacting with alkynyl-functionalized Wang resin. The obtained Y-shaped miktoarm star polypeptide copolymer was characterized by gel permeation chromatograph (GPC), Fourier transform-infrared spectroscopy (FT-IR), and (1)H NMR. Moreover, after the hydrolysis of protecting benzyl and benzyloxycarbonyl groups of PZLL-b-(PBLG)2, water-soluble pH-responsive Y-shaped miktoarm star polypeptide copolymer, PLL-b-(PLGA)2, was obtained, where PLL is poly(L-lysine) and PLGA is poly(L-glutamic acid). It can self-assemble into PLGA-core micelles at acidic pH and PLL-core micelles at alkaline pH, accompanied with the coil-to-helix transition of PLGA and PLL sequences, respectively. The spontaneous pH-responsive supramolecular assembly of PLL-b-(PLGA)2 miktoarm star polypeptide copolymer has been investigated via a combination of (1)H NMR, laser light scattering (LLS), transmission electron microscopy (TEM), and circular dichroism (CD) spectroscopy.

Synthesis and characterization of poly-L-leucine initialized and immobilized by rehydrated hydrotalcite: understanding stability and the nature of interaction.

PubMed

Miranda, Ronald-Alexander; Finocchio, Elisabetta; Llorca, Jordi; Medina, Francisco; Ramis, Gianguido; Sueiras, Jesús E; Segarra, Anna M

2013-10-07

PLLs were synthesized by the ring-opening polycondensation (ROP) method using α-L-leucine N-carboxyanhydride (NCA) and initialized by triethylamine (Et3N), water or rehydrated hydrotalcite (HTrus). The role of temperature, different initiators and water in ROP was further investigated. In general, the initiators used in the polymerization reaction lead to PLL alpha-helical chains containing 5-40 monomers with NCA endgroups via a monomer-activated mechanism. However, the water has a twofold effect on ROP, as both a nucleophile and a base, which involves competition between two different types of initiating mechanisms (nucleophilic attack or deprotonation of the NCA monomer) in the polymerization reaction. This competition provides as a main product NCA endgroups with an alpha-helical structure and leads to the formation of the PLL cyclic-chains and beta-sheet structures which reduce the polymer Mw and the PD of the polypeptide. Furthermore, the water can hydrolyze the NCA endgroups resulting in PLL alpha-helical chains that contain living groups as the main product. On the other hand, the HTrus presents a double role: as both an initiator and a support. The polymers synthesized in the presence of HTrus presented a HT-carboxylate endgroup. The PLLs immobilized in HTrus through an anion-exchange method performed for just 30 minutes presented the PLL immobilized in the interlayer space of the HTrus. The PLL chains of the immobilized counterpart are stabilized by H-bonding with the M-OH of the HT structure. All the polypeptides and biohybrid materials synthesized have been characterized using different techniques (EA, ICP, XRD, Raman, MALDI-TOF, ESI-TOF, FT-IR at increasing temperatures, TG/DT analyses and TEM).

ECL gate array with integrated PLL-based clock recovery and synthesis for high-speed data and telecom applications

NASA Astrophysics Data System (ADS)

Rosky, David S.; Coy, Bruce H.; Friedmann, Marc D.

1992-03-01

A 2500 gate mixed signal gate array has been developed that integrates custom PLL-based clock recovery and clock synthesis functions with 2500 gates of configurable logic cells to provide a single chip solution for 200 - 1244 MHz fiber based digital interface applications. By customizing the digital logic cells, any of the popular telecom and datacom standards may be implemented.

Alpha-helix to beta-sheet transition in long-chain poly-l-lysine: Formation of alpha-helical fibrils by poly-l-lysine.

PubMed

Cieślik-Boczula, Katarzyna

2017-06-01

The temperature-induced α-helix to β-sheet transition in long-chain poly-l-lysine (PLL), accompanied by the gauche-to-trans isomerization of CH 2 groups in the hydrocarbon side chains of Lys amino acid residues, and formation of β-sheet as well as α-helix fibrillar aggregates of PLL have been studied using Fourier-transform infrared (FT-IR) and vibrational circular dichroism (VCD) spectroscopy, and transmission electron microscopy (TEM). In a low-temperature alkaline water solution or in a methanol-rich water mixture, the secondary structure of PLL is represented by α-helical conformations with unordered and gauche-rich hydrocarbon side chains. Under these conditions, PLL molecules aggregate into α-helical fibrils. PLLs dominated by extended antiparallel β-sheet structures with highly ordered trans-rich hydrocarbon side chains are formed in a high-temperature range at alkaline pD and aggregate into fibrillar, protofibrillar, and spherical forms. Presented data support the idea that fibrillar aggregation is a varied phenomenon possible in repetitive structural elements with not only a β-sheet-rich conformation, but also an α-helical-rich conformation. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

CMOS serial link for fully duplexed data communication

NASA Astrophysics Data System (ADS)

Lee, Kyeongho; Kim, Sungjoon; Ahn, Gijung; Jeong, Deog-Kyoon

1995-04-01

This paper describes a CMOS serial link allowing fully duplexed 500 Mbaud serial data communication. The CMOS serial link is a robust and low-cost solution to high data rate requirements. A central charge pump PLL for generating multiphase clocks for oversampling is shared by several serial link channels. Fully duplexed serial data communication is realized in the bidirectional bridge by separating incoming data from the mixed signal on the cable end. The digital PLL accomplishes process-independent data recovery by using a low-ratio oversampling, a majority voting, and a parallel data recovery scheme. Mostly, digital approach could extend its bandwidth further with scaled CMOS technology. A single channel serial link and a charge pump PLL are integrated in a test chip using 1.2 micron CMOS process technology. The test chip confirms upto 500 Mbaud unidirectional mode operation and 320 Mbaud fully duplexed mode operation with pseudo random data patterns.

Nano-patterned SU-8 surface using nanosphere-lithography for enhanced neuronal cell growth

NASA Astrophysics Data System (ADS)

Kim, Eunhee; Yoo, Seung-Jun; Kim, Eunjung; Kwon, Tae-Hwan; Zhang, Li; Moon, Cheil; Choi, Hongsoo

2016-04-01

Mimicking the nanoscale surface texture of the extracellular matrix can affect the regulation of cellular behavior, including adhesion, differentiation, and neurite outgrowth. In this study, SU-8-based polymer surfaces with well-ordered nanowell arrays were fabricated using nanosphere lithography with polystyrene nanoparticles. We show that the SU-8 surface with nanowells resulted in similar neuronal development of rat pheochromocytoma (PC12) cells compared with an unpatterned poly-L-lysine (PLL)-coated SU-8 surface. Additionally, even after soaking the substrate in cell culture medium for two weeks, cells on the nanowell SU-8 surface showed long-term neurite outgrowth compared to cells on the PLL-coated SU-8 surface. The topographical surface modification of the nanowell array demonstrates potential as a replacement for cell adhesive material coatings such as PLL, for applications requiring long-term use of polymer-based implantable devices.

Comparison of user volume control settings for portable music players with three earphone configurations in quiet and noisy environments.

PubMed

Henry, Paula; Foots, Ashley

2012-03-01

Listening to music is one of the most common forms of recreational noise exposure. Previous investigators have demonstrated that maximum output levels from headphones can exceed safe levels. Although preferred listening levels (PLL) in quiet environments may be at acceptable levels, the addition of background noise will add to the overall noise exposure of a listener. Use of listening devices that block out some of the background noise would potentially allow listeners to select lower PLLs for their music. Although one solution is in-the-ear earphones, an alternative solution is the use of earmuffs in conjunction with earbuds. There were two objectives to this experiment. The first was to determine if an alternative to in-the-ear earphones for noise attenuation (the addition of earmuffs to earbuds) would allow for lower PLLs through a portable media player (PMP) than earbuds. The second was to determine if a surrounding background noise would yield different PLLs than a directional noise source. This was an experimental study. Twenty-four adults with normal hearing. PLLs were measured for three earphone configurations in three listening conditions. The earphone configurations included earbuds, canal earphones, and earbuds in combination with hearing protection devices (HPDs). The listening conditions included quiet, noise from one loudspeaker, and noise from four surrounding loudspeakers. Participants listened in each noise and earphone combination for as long as they needed to determine their PLL for that condition. Once the participant determined their PLL, investigators made a 5 sec recording of the music through a probe tube microphone. The average PLLs in each noise and earphone combination were used as the dependent variable. Ear canal level PLLs were converted to free-field equivalents to compare to noise exposure standards and previously published data. The average PLL as measured in the ear canal was 74 dBA in the quiet conditions and 84 dBA in the noise conditions. Paired comparisons of the PLL in the presence of background noise for each pair of earphone configurations indicated significant differences for each comparison. An inverse relationship was observed between attenuation and PLL whereby the greater the attenuation, the lower the PLL. A comparison of the single noise source condition versus the surrounding noise condition did not result in a significant effect. The present work suggests that earphones that take advantage of noise attenuation can reduce the level at which listeners set music in the presence of background noise. An alternative to in-the-ear earphones for noise attenuation is the addition of earmuffs to earbuds. American Academy of Audiology.

Centering a DDR Strobe in the Middle of a Data Packet

NASA Technical Reports Server (NTRS)

Johnson, Michael; Nelson, Dave; Seefeldt, James; Roper, Weston; Passow, Craig

2014-01-01

The Orion CEV Northstar ASIC (application- specific integrated circuit) project required a DDR (double data rate) memory bus driver/receiver (DDR PHY block) to interface with external DDR memory. The DDR interface (JESD79C) is based on a source synchronous strobe (DQS\\) that is sent along with each packet of data (DQ). New data is provided concurrently with each edge of strobe and is sent irregularly. In order to capture this data, the strobe needs to be delayed and used to latch the data into a register. A circuit solves the need for training a DDR PRY block by incorporating a PVT-compensated delay element in the strobe path. This circuit takes an external reference clock signal and uses the regular clock to calibrate a known delay through a data path. The compensated delay DQS signal is then used to capture the DQ data in a normal register. This register structure can be configured as a FIFO (first in first out), in order to transfer data from the DDR domain to the system clock domain. This design is different in that it does not rely upon the need for training the system response, nor does it use a PLL (phase locked loop) or a DLL (delay locked loop) to provide an offset of the strobe signal. The circuit is created using standard ASIC building blocks, plus the PVT (process, voltage, and temperature) compensated delay line. The design uses a globally available system clock as a reference, alleviating the need to operate synchronously with the remote memory. The reference clock conditions the PVT compensated delay line to provide a pre-determined amount of delay to any data signal that passes through this delay line. The delay line is programmed in degrees of offset, so that one could think of the clock period representing 360deg of delay. In an ideal environment, delaying the strobe 1/4 of a clock cycle (90deg) would place the strobe in the middle of the data packet. This delayed strobe can then be used to clock the data into a register, satisfying setup and hold requirements of the system.

Prolymphocytic leukaemia: surface morphology in 21 cases as seen by scanning electron microscopy and comparison with B-type CLL and CLL in 'prolymphocytoid' transformation.

PubMed

Polliack, A; Leizerowitz, R; Berrebi, A; Gamliel, H; Galili, N; Gurfel, D; Catovsky, D

1984-08-01

The surface architecture of leukaemic cells obtained from 21 cases of proven prolymphocytic leukaemia (PLL) and eight cases of chronic lymphocytic leukaemia (CLL) with 'prolymphocytoid' transformation (PL-CLL) was compared with the cell surface morphology of leukaemic cells obtained from 46 cases of B-type CLL, using the scanning electron microscope (SEM). All cases were defined by cytochemistry, immunological markers and transmission electron microscopy prior to SEM examination. B-CLL cells showed the well-recognized spectrum of surface architecture described in earlier studies. The majority of cells had moderate numbers of short microvilli, although in a minority, cells with relatively smooth surfaces predominated. In seven of the eight cases of PL-CLL, cells were villous in nature and in this respect similar to CLL cells; however, more cells with dense microvilli were seen. The prolymphocytic cells were recognized by their larger size and in 18 of the 19 cases of B-derived PLL, villous cells predominated. Two cases of T-derived PLL showed variable cell surface morphology ranging from smooth to moderately villous. It appears that B-PLL cells are most frequently villous and display more surface microvilli than B-CLL cells. B-prolymphocytes display the surface features regarded as characteristic for neoplastic B-cells as seen in patients with B-type lymphoma and leukaemia.

Gold Nanoparticles Stabilized with MPEG-Grafted Poly(l-lysine): in Vitro and in Vivo Evaluation of a Potential Theranostic Agent

PubMed Central

2015-01-01

As the number of diagnostic and therapeutic applications utilizing gold nanoparticles (AuNPs) increases, so does the need for AuNPs that are stable in vivo, biocompatible, and suitable for bioconjugation. We investigated a strategy for AuNP stabilization that uses methoxypolyethylene glycol-graft-poly(l-lysine) copolymer (MPEG-gPLL) bearing free amino groups as a stabilizing molecule. MPEG-gPLL injected into water solutions of HAuCl4 with or without trisodium citrate resulted in spherical (Zav = 36 nm), monodisperse (PDI = 0.27), weakly positively charged nanoparticles (AuNP3) with electron-dense cores (diameter: 10.4 ± 2.5 nm) and surface amino groups that were amenable to covalent modification. The AuNP3 were stable against aggregation in the presence of phosphate and serum proteins and remained dispersed after their uptake into endosomes. MPEG-gPLL-stabilized AuNP3 exhibited high uptake and very low toxicity in human endothelial cells, but showed a high dose-dependent toxicity in epithelioid cancer cells. Highly stable radioactive labeling of AuNP3 with 99mTc allowed imaging of AuNP3 biodistribution and revealed dose-dependent long circulation in the blood. The minor fraction of AuGNP3 was found in major organs and at sites of experimentally induced inflammation. Gold analysis showed evidence of a partial degradation of the MPEG-gPLL layer in AuNP3 particles accumulated in major organs. Radiofrequency-mediated heating of AuNP3 solutions showed that AuNP3 exhibited heating behavior consistent with 10 nm core nanoparticles. We conclude that PEG-pPLL coating of AuNPs confers “stealth” properties that enable these particles to exist in vivo in a nonaggregating, biocompatible state making them suitable for potential use in biomedical applications such as noninvasive radiofrequency cancer therapy. PMID:25496453

Femtogram Mass Biosensor Using Self-Sensing Cantilever for Allergy Check

NASA Astrophysics Data System (ADS)

Sone, Hayato; Ikeuchi, Ayumi; Izumi, Takashi; Okano, Haruki; Hosaka, Sumio

2006-03-01

A self-sensing mass biosensor with a femtogram mass sensitivity has been developed using a piezoresistive microcantilever. The mass change due to antigen and antibody adsorption on the cantilever in water was detected by the resonance frequency shift of the cantilever. We constructed a prototype harmonic vibration sensor using a commercial piezoresistive cantilever, Wheatstone bridge circuits, a positive feedback controller, an exciting piezoactuator and a phase-locked loop (PLL) demodulator. As experimental results, a mass sensitivity of about 190 fg/Hz, and a mass resolution of about 500 fg were obtained in water. The mass sensitivity is 100 times higher than that of a quartz crystal oscillation method. We demonstrated that the sensor can detect the reaction between an antibody of immunoglobulin (IgG) and an antigen of egg albumen (OVA). We confirmed that the binding ratio between the antibody and the antigen was about 1 : 2. The detection method is available for allergy check because the measured reaction ratio occurring on the cantilever concurs with the theoretical method.

VCSEL-based optical transceiver module operating at 25 Gb/s and using a single CMOS IC

NASA Astrophysics Data System (ADS)

Afriat, Gil; Horwitz, Lior; Lazar, Dror; Issachar, Assaf; Pogrebinsky, Alexander; Ran, Adee; Shoor, Ehud; Bar, Roi; Saba, Rushdy

2012-01-01

We present here a low cost, small form factor, optical transceiver module composed of a CMOS IC transceiver, 850 nm emission wavelength VCSEL modulated at 25 Gb/s, and an InGaAs/InP PIN Photo Diode (PD). The transceiver IC is fabricated in a standard 28 nm CMOS process and integrates the analog circuits interfacing the VCSEL and PD, namely the VCSEL driver and Transimpedance Amplifier (TIA), as well as all other required transmitter and receiver circuits like Phase Locked Loop (PLL), Post Amplifier and Clock & Data Recovery (CDR). The transceiver module couples into a 62.5/125 um multi-mode (OM1) TX/RX fiber pair via a low cost plastic cover realizing the transmitter and receiver lens systems and demonstrates BER < 10-12 at the 25 Gb/s data rate over a distance of 3 meters. Using a 50/125 um laser optimized multi-mode fiber (OM3), the same performance was achieved over a distance of 30 meters.

Novel Concrete Temperature Monitoring Method Based on an Embedded Passive RFID Sensor Tag.

PubMed

Liu, Yongsheng; Deng, Fangming; He, Yigang; Li, Bing; Liang, Zhen; Zhou, Shuangxi

2017-06-22

This paper firstly introduces the importance of temperature control in concrete measurement, then a passive radio frequency identification (RFID) sensor tag embedded for concrete temperature monitoring is presented. In order to reduce the influences of concrete electromagnetic parameters during the drying process, a T-type antenna is proposed to measure the concrete temperature at the required depth. The proposed RFID sensor tag is based on the EPC generation-2 ultra-high frequency (UHF) communication protocol and operates in passive mode. The temperature sensor can convert the sensor signals to corresponding digital signals without an external reference clock due to the adoption of phase-locked loop (PLL)-based architecture. Laboratory experimentation and on-site testing demonstrate that our sensor tag embedded in concrete can provide reliable communication performance in passive mode. The maximum communicating distance between reader and tag is 7 m at the operating frequency of 915 MHz and the tested results show high consistency with the results tested by a thermocouple.

Chip Scale Atomic Resonator Frequency Stabilization System With Ultra-Low Power Consumption for Optoelectronic Oscillators.

PubMed

Zhao, Jianye; Zhang, Yaolin; Lu, Haoyuan; Hou, Dong; Zhang, Shuangyou; Wang, Zhong

2016-07-01

We present a long-term chip scale stabilization scheme for optoelectronic oscillators (OEOs) based on a rubidium coherent population trapping (CPT) atomic resonator. By locking a single mode of an OEO to the (85)Rb 3.035-GHz CPT resonance utilizing an improved phase-locked loop (PLL) with a PID regulator, we achieved a chip scale frequency stabilization system for the OEO. The fractional frequency stability of the stabilized OEO by overlapping Allan deviation reaches 6.2 ×10(-11) (1 s) and  ∼ 1.45 ×10 (-11) (1000 s). This scheme avoids a decrease in the extra phase noise performance induced by the electronic connection between the OEO and the microwave reference in common injection locking schemes. The total physical package of the stabilization system is [Formula: see text] and the total power consumption is 400 mW, which provides a chip scale and portable frequency stabilization approach with ultra-low power consumption for OEOs.

Novel Concrete Temperature Monitoring Method Based on an Embedded Passive RFID Sensor Tag

PubMed Central

Liu, Yongsheng; Deng, Fangming; He, Yigang; Li, Bing; Liang, Zhen; Zhou, Shuangxi

2017-01-01

This paper firstly introduces the importance of temperature control in concrete measurement, then a passive radio frequency identification (RFID) sensor tag embedded for concrete temperature monitoring is presented. In order to reduce the influences of concrete electromagnetic parameters during the drying process, a T-type antenna is proposed to measure the concrete temperature at the required depth. The proposed RFID sensor tag is based on the EPC generation-2 ultra-high frequency (UHF) communication protocol and operates in passive mode. The temperature sensor can convert the sensor signals to corresponding digital signals without an external reference clock due to the adoption of phase-locked loop (PLL)-based architecture. Laboratory experimentation and on-site testing demonstrate that our sensor tag embedded in concrete can provide reliable communication performance in passive mode. The maximum communicating distance between reader and tag is 7 m at the operating frequency of 915 MHz and the tested results show high consistency with the results tested by a thermocouple. PMID:28640188

Target-specific cellular uptake of PLGA nanoparticles coated with poly(L-lysine)-poly(ethylene glycol)-folate conjugate.

PubMed

Kim, Sun Hwa; Jeong, Ji Hoon; Chun, Ki Woo; Park, Tae Gwan

2005-09-13

Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles with anionic surface charge were surface coated with cationic di-block copolymer, poly(L-lysine)-poly(ethylene glycol)-folate (PLL-PEG-FOL) conjugate, for enhancing their site-specific intracellular delivery against folate receptor overexpressing cancer cells. The PLGA nanoparticles coated with the conjugate were characterized in terms of size, surface charge, and change in surface composition by XPS. By employing the flow cytometry method and confocal image analysis, the extent of cellular uptake was comparatively evaluated under various conditions. PLL-PEG-FOL coated PLGA nanoparticles demonstrated far greater extent of cellular uptake to KB cells, suggesting that they were mainly taken up by folate receptor-mediated endocytosis. The enhanced cellular uptake was also observed even in the presence of serum proteins, possibly due to the densely seeded PEG chains. The PLL-PEG-FOL coated PLGA nanoparticles could be potentially applied for cancer cell targeted delivery of various therapeutic agents.

The effect of magnetic nanoparticles on neuronal differentiation of induced pluripotent stem cell-derived neural precursors

PubMed Central

Jiráková, Klára; Šeneklová, Monika; Jirák, Daniel; Turnovcová, Karolína; Vosmanská, Magda; Babič, Michal; Horák, Daniel; Veverka, Pavel; Jendelová, Pavla

2016-01-01

Introduction Magnetic resonance (MR) imaging is suitable for noninvasive long-term tracking. We labeled human induced pluripotent stem cell-derived neural precursors (iPSC-NPs) with two types of iron-based nanoparticles, silica-coated cobalt zinc ferrite nanoparticles (CZF) and poly-l-lysine-coated iron oxide superparamagnetic nanoparticles (PLL-coated γ-Fe2O3) and studied their effect on proliferation and neuronal differentiation. Materials and methods We investigated the effect of these two contrast agents on neural precursor cell proliferation and differentiation capability. We further defined the intracellular localization and labeling efficiency and analyzed labeled cells by MR. Results Cell proliferation was not affected by PLL-coated γ-Fe2O3 but was slowed down in cells labeled with CZF. Labeling efficiency, iron content and relaxation rates measured by MR were lower in cells labeled with CZF when compared to PLL-coated γ-Fe2O3. Cytoplasmic localization of both types of nanoparticles was confirmed by transmission electron microscopy. Flow cytometry and immunocytochemical analysis of specific markers expressed during neuronal differentiation did not show any significant differences between unlabeled cells or cells labeled with both magnetic nanoparticles. Conclusion Our results show that cells labeled with PLL-coated γ-Fe2O3 are suitable for MR detection, did not affect the differentiation potential of iPSC-NPs and are suitable for in vivo cell therapies in experimental models of central nervous system disorders. PMID:27920532

Reference clock parameters for digital communications systems applications

NASA Technical Reports Server (NTRS)

Kartaschoff, P.

1981-01-01

The basic parameters relevant to the design of network timing systems describe the random and systematic time departures of the system elements, i.e., master (or reference) clocks, transmission links, and other clocks controlled over the links. The quantitative relations between these parameters were established and illustrated by means of numerical examples based on available measured data. The examples were limited to a simple PLL control system but the analysis can eventually be applied to more sophisticated systems at the cost of increased computational effort.

Optimization of Polyplex Formation between DNA Oligonucleotide and Poly(ʟ-Lysine): Experimental Study and Modeling Approach.

PubMed

Vasiliu, Tudor; Cojocaru, Corneliu; Rotaru, Alexandru; Pricope, Gabriela; Pinteala, Mariana; Clima, Lilia

2017-06-17

The polyplexes formed by nucleic acids and polycations have received a great attention owing to their potential application in gene therapy. In our study, we report experimental results and modeling outcomes regarding the optimization of polyplex formation between the double-stranded DNA (dsDNA) and poly(ʟ-Lysine) (PLL). The quantification of the binding efficiency during polyplex formation was performed by processing of the images captured from the gel electrophoresis assays. The design of experiments (DoE) and response surface methodology (RSM) were employed to investigate the coupling effect of key factors (pH and N/P ratio) affecting the binding efficiency. According to the experimental observations and response surface analysis, the N/P ratio showed a major influence on binding efficiency compared to pH. Model-based optimization calculations along with the experimental confirmation runs unveiled the maximal binding efficiency (99.4%) achieved at pH 5.4 and N/P ratio 125. To support the experimental data and reveal insights of molecular mechanism responsible for the polyplex formation between dsDNA and PLL, molecular dynamics simulations were performed at pH 5.4 and 7.4.

Optimization of Polyplex Formation between DNA Oligonucleotide and Poly(l-Lysine): Experimental Study and Modeling Approach

PubMed Central

Vasiliu, Tudor; Cojocaru, Corneliu; Rotaru, Alexandru; Pricope, Gabriela; Pinteala, Mariana; Clima, Lilia

2017-01-01

The polyplexes formed by nucleic acids and polycations have received a great attention owing to their potential application in gene therapy. In our study, we report experimental results and modeling outcomes regarding the optimization of polyplex formation between the double-stranded DNA (dsDNA) and poly(l-Lysine) (PLL). The quantification of the binding efficiency during polyplex formation was performed by processing of the images captured from the gel electrophoresis assays. The design of experiments (DoE) and response surface methodology (RSM) were employed to investigate the coupling effect of key factors (pH and N/P ratio) affecting the binding efficiency. According to the experimental observations and response surface analysis, the N/P ratio showed a major influence on binding efficiency compared to pH. Model-based optimization calculations along with the experimental confirmation runs unveiled the maximal binding efficiency (99.4%) achieved at pH 5.4 and N/P ratio 125. To support the experimental data and reveal insights of molecular mechanism responsible for the polyplex formation between dsDNA and PLL, molecular dynamics simulations were performed at pH 5.4 and 7.4. PMID:28629130

A 2x2 W-Band Reference Time-Shifted Phase-Locked Transmitter Array in 65nm CMOS Technology

NASA Technical Reports Server (NTRS)

Tang, Adrian; Virbila, Gabriel; Hsiao, Frank; Wu, Hao; Murphy, David; Mehdi, Imran; Siegel, P. H.; Chang, M-C. Frank

2013-01-01

This paper presents a complete 2x2 phased array transmitter system operating at W-band (90-95 GHz) which employs a PLL reference time-shifting approach instead of using traditional mm-wave phase shifters. PLL reference shifting enables a phased array to be distributed over multiple chips without the need for coherent mm-wave signal distribution between chips. The proposed phased array transmitter system consumes 248 mW per array element when implemented in a 65 nm CMOS technology.

Analysis, design, and control of a transcutaneous power regulator for artificial hearts.

PubMed

Qianhong Chen; Siu Chung Wong; Tse, C K; Xinbo Ruan

2009-02-01

Based on a generic transcutaneous transformer model, a remote power supply using a resonant topology for use in artificial hearts is analyzed and designed for easy controllability and high efficiency. The primary and secondary windings of the transcutaneous transformer are positioned outside and inside the human body, respectively. In such a transformer, the alignment and gap may change with external positioning. As a result, the coupling coefficient of the transcutaneous transformer is also varying, and so are the two large leakage inductances and the mutual inductance. Resonant-tank circuits with varying resonant-frequency are formed from the transformer inductors and external capacitors. For a given range of coupling coefficients, an operating frequency corresponding to a particular coupling coefficient can be found, for which the voltage transfer function is insensitive to load. Prior works have used frequency modulation to regulate the output voltage under varying load and transformer coupling. The use of frequency modulation may require a wide control frequency range which may extend well above the load insensitive frequency. In this paper, study of the input-to-output voltage transfer function is carried out, and a control method is proposed to lock the switching frequency at just above the load insensitive frequency for optimized efficiency at heavy loads. Specifically, operation at above resonant of the resonant circuits is maintained under varying coupling-coefficient. Using a digital-phase-lock-loop (PLL), zero-voltage switching is achieved in a full-bridge converter which is also programmed to provide output voltage regulation via pulsewidth modulation (PWM). A prototype transcutaneous power regulator is built and found to to perform excellently with high efficiency and tight regulation under variations of the alignment or gap of the transcutaneous transformer, load and input voltage.

A multi-channel low-power system-on-chip for single-unit recording and narrowband wireless transmission of neural signal.

PubMed

Bonfanti, A; Ceravolo, M; Zambra, G; Gusmeroli, R; Spinelli, A S; Lacaita, A L; Angotzi, G N; Baranauskas, G; Fadiga, L

2010-01-01

This paper reports a multi-channel neural recording system-on-chip (SoC) with digital data compression and wireless telemetry. The circuit consists of a 16 amplifiers, an analog time division multiplexer, an 8-bit SAR AD converter, a digital signal processor (DSP) and a wireless narrowband 400-MHz binary FSK transmitter. Even though only 16 amplifiers are present in our current die version, the whole system is designed to work with 64 channels demonstrating the feasibility of a digital processing and narrowband wireless transmission of 64 neural recording channels. A digital data compression, based on the detection of action potentials and storage of correspondent waveforms, allows the use of a 1.25-Mbit/s binary FSK wireless transmission. This moderate bit-rate and a low frequency deviation, Manchester-coded modulation are crucial for exploiting a narrowband wireless link and an efficient embeddable antenna. The chip is realized in a 0.35- εm CMOS process with a power consumption of 105 εW per channel (269 εW per channel with an extended transmission range of 4 m) and an area of 3.1 × 2.7 mm(2). The transmitted signal is captured by a digital TV tuner and demodulated by a wideband phase-locked loop (PLL), and then sent to a PC via an FPGA module. The system has been tested for electrical specifications and its functionality verified in in-vivo neural recording experiments.

Reduced-Order Structure-Preserving Model for Parallel-Connected Three-Phase Grid-Tied Inverters: Preprint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, Brian B; Purba, Victor; Jafarpour, Saber

Given that next-generation infrastructures will contain large numbers of grid-connected inverters and these interfaces will be satisfying a growing fraction of system load, it is imperative to analyze the impacts of power electronics on such systems. However, since each inverter model has a relatively large number of dynamic states, it would be impractical to execute complex system models where the full dynamics of each inverter are retained. To address this challenge, we derive a reduced-order structure-preserving model for parallel-connected grid-tied three-phase inverters. Here, each inverter in the system is assumed to have a full-bridge topology, LCL filter at the pointmore » of common coupling, and the control architecture for each inverter includes a current controller, a power controller, and a phase-locked loop for grid synchronization. We outline a structure-preserving reduced-order inverter model for the setting where the parallel inverters are each designed such that the filter components and controller gains scale linearly with the power rating. By structure preserving, we mean that the reduced-order three-phase inverter model is also composed of an LCL filter, a power controller, current controller, and PLL. That is, we show that the system of parallel inverters can be modeled exactly as one aggregated inverter unit and this equivalent model has the same number of dynamical states as an individual inverter in the paralleled system. Numerical simulations validate the reduced-order models.« less

Leptin and leptin receptor gene polymorphisms and their association with plasma leptin levels and obesity in a multi-ethnic Malaysian suburban population.

PubMed

Fan, Sook-Ha; Say, Yee-How

2014-06-20

This study was to investigate the prevalence of single nucleotide polymorphisms (SNPs) in leptin gene LEP (A19G and G2548A) and leptin receptor gene LEPR (K109R and Q223R) and their association with fasting plasma leptin level (PLL) and obesity in a Malaysian suburban population in Kampar, Perak. Convenience sampling was performed with informed consents, and the study sample was drawn from patients who were patrons of the Kampar Health Clinic. A total of 408 subjects (mean age, 52.4 ± 13.7 years; 169 men, 239 women; 190 obese, 218 non-obese; 148 Malays, 177 ethnic Chinese, 83 ethnic Indians) participated. Socio-demographic data and anthropometric measurements were taken, and genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The LEP A19G, G2548A and LEPR K109R, Q223R variant allele frequencies were 0.74, 0.67 and 0.61, 0.79, respectively. The genotype and allele distributions of these gene variants were significantly different among ethnic groups, but not among body mass index (BMI) classes. Subjects with LEPR K109 and Q223 allele had significantly higher systolic blood pressure and adiposity indices after adjustment for ethnicity (higher BMI, total body and subcutaneous fat; lower skeletal muscle percentage). Subjects with LEPR 109R allele had lower PLL than their wild-type allele counterparts. The influence of LEP A19G and G2548A SNPs on blood pressures, anthropometrics, and PLL was not evident. Interestingly, synergistic effect of the LEP and LEPR SNPs was observed as subjects homozygous for all four SNPs studied exhibited significantly higher subcutaneous fat and PLL than those with other genotype combinations. The LEP and LEPR SNPs in this study may not be an obesity marker among Malaysians in this population, but were associated with ethnicity. Our findings suggest that each of these SNPs contributes to minor but significant variation in obesity-related traits and in combination they display synergistic effects on subcutaneous fat and PLL.

Leptin and leptin receptor gene polymorphisms and their association with plasma leptin levels and obesity in a multi-ethnic Malaysian suburban population

PubMed Central

2014-01-01

Background This study was to investigate the prevalence of single nucleotide polymorphisms (SNPs) in leptin gene LEP (A19G and G2548A) and leptin receptor gene LEPR (K109R and Q223R) and their association with fasting plasma leptin level (PLL) and obesity in a Malaysian suburban population in Kampar, Perak. Methods Convenience sampling was performed with informed consents, and the study sample was drawn from patients who were patrons of the Kampar Health Clinic. A total of 408 subjects (mean age, 52.4 ± 13.7 years; 169 men, 239 women; 190 obese, 218 non-obese; 148 Malays, 177 ethnic Chinese, 83 ethnic Indians) participated. Socio-demographic data and anthropometric measurements were taken, and genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results The LEP A19G, G2548A and LEPR K109R, Q223R variant allele frequencies were 0.74, 0.67 and 0.61, 0.79, respectively. The genotype and allele distributions of these gene variants were significantly different among ethnic groups, but not among body mass index (BMI) classes. Subjects with LEPR K109 and Q223 allele had significantly higher systolic blood pressure and adiposity indices after adjustment for ethnicity (higher BMI, total body and subcutaneous fat; lower skeletal muscle percentage). Subjects with LEPR 109R allele had lower PLL than their wild-type allele counterparts. The influence of LEP A19G and G2548A SNPs on blood pressures, anthropometrics, and PLL was not evident. Interestingly, synergistic effect of the LEP and LEPR SNPs was observed as subjects homozygous for all four SNPs studied exhibited significantly higher subcutaneous fat and PLL than those with other genotype combinations. Conclusions The LEP and LEPR SNPs in this study may not be an obesity marker among Malaysians in this population, but were associated with ethnicity. Our findings suggest that each of these SNPs contributes to minor but significant variation in obesity-related traits and in combination they display synergistic effects on subcutaneous fat and PLL. PMID:24947733

Determination of IgE antibodies to the benzylpenicilloyl determinant: a comparison of the sensitivity and specificity of three radio allergo sorbent test methods.

PubMed

Garcia, J J; Blanca, M; Moreno, F; Vega, J M; Mayorga, C; Fernandez, J; Juarez, C; Romano, A; de Ramon, E

1997-01-01

The quantitation of in vitro IgE antibodies to the benzylpenicilloyl determinant (BPO) is a useful tool for evaluating suspected penicillin allergic subjects. Although many different methods have been employed, few studies have compared their diagnostic specificity and sensitivity. In this study, the sensitivity and specificity of three different radio allergo sorbent test (RAST) methods for quantitating specific IgE antibodies to the BPO determinant were compared. Thirty positive control sera (serum samples from penicillin allergic subjects with a positive clinical history and a positive penicillin skin test) and 30 negative control sera (sera from subjects with no history of penicillin allergy and negative skin tests) were tested for BPO-specific IgE antibodies by RAST using three different conjugates coupled to the solid phase: benzylpenicillin conjugated to polylysine (BPO-PLL), benzylpenicillin conjugated to human serum albumin (BPO-HSA), and benzylpenicillin conjugated to an aminospacer (BPO-SP). Receiver operator control curves (ROC analysis) were carried out by determining different cut-off points between positive and negative values. Contingence tables were constructed and sensitivity, specificity, negative predictive values (PV-), and positive predictive values (PV+) were calculated. Pearson correlation coefficients (r) and intraclass correlation coefficients (ICC) were determined and the differences between methods were compared by chi 2 analysis. Analysis of the areas defined by the ROC curves showed statistical differences among the three methods. When cut-off points for optimal sensitivity and specificity were chosen, the BPO-HSA assay was less sensitive and less specific and had a lower PV- and PV+ than the BPO-PLL and BPO-SP assays. Assessment of r and ICC indicated that the correlation was very high, but the concordance between the PLL and SP methods was higher than between the PLL and HSA or SP and HSA methods. We conclude that for quantitating IgE antibodies by RAST to the BPO determinant, BPO-SP or BPO-PLL conjugates offer advantages in sensitivity and specificity compared with BPO-HSA. These results support and extend previous in vitro studies by our group and highlight the importance of the carrier for RAST assays.

Antimicrobial coatings on polyethylene terephthalate based on curcumin/cyclodextrin complex embedded in a multilayer polyelectrolyte architecture.

PubMed

Shlar, Ilya; Droby, Samir; Rodov, Victor

2018-04-01

Bacterial contamination is a growing concern worldwide. The aim of this work was to develop an antimicrobial coating based on curcumin-cyclodextrin inclusion complex and using polyethylene terephthalate (PET) film as a support matrix. After a pre-treatment aimed to provide sufficient electric charge to the PET surface, it was electrostatically coated with repeated multilayers comprising alternately deposited positively-charged poly-l-lysine (PLL) and negatively-charged poly-l-glutamic acid (PLGA) and carboxymethyl-β-cyclodextrin (CMBCD). The coatings had an architecture (PLL-PLGA) 6 -(PLL-PLGA-PLL-CMBCD) n , with the number of repeated multilayers n varying from 5 to 20. The CMBCD molecules were either covalently cross-linked using carbodiimide crosslinker chemistry or left unbound. The surface morphology, structure and elemental composition of the coatings were analysed by scanning electron microscopy and energy dispersive x-ray spectroscopy. To impart antimicrobial properties to the coatings they were loaded with a natural phenolic compound curcumin forming inclusion complexes with β-cyclodextrin. The non-cross-linked coatings showed bactericidal activity towards Escherichia coli in the dark, and this activity was further enhanced upon illumination with white light. Curcumin was released from the non-cross-linked coatings into an aqueous medium in the form of cyclodextrin inclusion complex. After the cross-linking, the coating lost its dark antimicrobial activity but retained the photodynamic properties. Stabilized cross-linked curcumin-loaded coatings can serve a basis for developing photoactivated antimicrobial surfaces controlling bacterial contamination and spread. Copyright © 2018 Elsevier B.V. All rights reserved.

Structural basis for regulation of GPR56/ADGRG1 by its alternatively spliced extracellular domains

PubMed Central

Salzman, Gabriel S.; Ackerman, Sarah D.; Ding, Chen; Koide, Akiko; Leon, Katherine; Luo, Rong; Stoveken, Hannah M.; Fernandez, Celia G.; Tall, Gregory G.; Piao, Xianhua; Monk, Kelly R.; Koide, Shohei; Araç, Demet

2016-01-01

Summary Adhesion G-protein-coupled receptors (aGPCRs) play critical roles in diverse neurobiological processes including brain development, synaptogenesis, and myelination. aGPCRs have large alternatively spliced extracellular regions (ECRs) that likely mediate intercellular signaling; however, the precise roles of ECRs remain unclear. The aGPCR GPR56/ADGRG1 regulates both oligodendrocyte and cortical development. Accordingly, human GPR56 mutations cause myelination defects and brain malformations. Here, we determined the crystal structure of the GPR56 ECR, the first structure of any complete aGPCR ECR, in complex with an inverse-agonist monobody, revealing a GPCR-Autoproteolysis-Inducing domain and a previously unidentified domain that we term Pentraxin/Laminin/neurexin/sex-hormone-binding-globulin-Like (PLL). Strikingly, PLL domain deletion caused increased signaling and characterizes a GPR56 splice variant. Finally, we show that an evolutionarily conserved residue in the PLL domain is critical for oligodendrocyte development in vivo. Thus, our results suggest that the GPR56 ECR has unique and multifaceted regulatory functions, providing novel insights into aGPCR roles in neurobiology. PMID:27657451

Optimized labeling of bone marrow mesenchymal cells with superparamagnetic iron oxide nanoparticles and in vivo visualization by magnetic resonance imaging

PubMed Central

2011-01-01

Background Stem cell therapy has emerged as a promising addition to traditional treatments for a number of diseases. However, harnessing the therapeutic potential of stem cells requires an understanding of their fate in vivo. Non-invasive cell tracking can provide knowledge about mechanisms responsible for functional improvement of host tissue. Superparamagnetic iron oxide nanoparticles (SPIONs) have been used to label and visualize various cell types with magnetic resonance imaging (MRI). In this study we performed experiments designed to investigate the biological properties, including proliferation, viability and differentiation capacity of mesenchymal cells (MSCs) labeled with clinically approved SPIONs. Results Rat and mouse MSCs were isolated, cultured, and incubated with dextran-covered SPIONs (ferumoxide) alone or with poly-L-lysine (PLL) or protamine chlorhydrate for 4 or 24 hrs. Labeling efficiency was evaluated by dextran immunocytochemistry and MRI. Cell proliferation and viability were evaluated in vitro with Ki67 immunocytochemistry and live/dead assays. Ferumoxide-labeled MSCs could be induced to differentiate to adipocytes, osteocytes and chondrocytes. We analyzed ferumoxide retention in MSCs with or without mitomycin C pretreatment. Approximately 95% MSCs were labeled when incubated with ferumoxide for 4 or 24 hrs in the presence of PLL or protamine, whereas labeling of MSCs incubated with ferumoxide alone was poor. Proliferative capacity was maintained in MSCs incubated with ferumoxide and PLL for 4 hrs, however, after 24 hrs it was reduced. MSCs incubated with ferumoxide and protamine were efficiently visualized by MRI; they maintained proliferation and viability for up to 7 days and remained competent to differentiate. After 21 days MSCs pretreated with mitomycin C still showed a large number of ferumoxide-labeled cells. Conclusions The efficient and long lasting uptake and retention of SPIONs by MSCs using a protocol employing ferumoxide and protamine may be applicable to patients, since both ferumoxides and protamine are approved for human use. PMID:21542946

Hardware Verification of Laser Noise Cancellation and Gravitational Wave Extraction using Time-Delay Interferometry

NASA Astrophysics Data System (ADS)

Mitryk, Shawn; Mueller, Guido

The Laser Interferometer Space Antenna (LISA) is a space-based modified Michelson interfer-ometer designed to measure gravitational radiation in the frequency range from 30 uHz to 1 Hz. The interferometer measurement system (IMS) utilizes one-way laser phase measurements to cancel the laser phase noise, reconstruct the proof-mass motion, and extract the gravitational wave (GW) induced laser phase modulations in post-processing using a technique called time-delay interferometry (TDI). Unfortunately, there exist few hard-ware verification experiments of the IMS. The University of Florida LISA Interferometry Simulator (UFLIS) is designed to perform hardware-in-the-loop simulations of the LISA interferometry system, modeling the characteris-tics of the LISA mission as accurately as possible. This depends, first, on replicating the laser pre-stabilization by locking the laser phase to an ultra-stable Zerodur cavity length reference using the PDH locking method. Phase measurements of LISA-like photodetector beat-notes are taken using the UF-phasemeter (PM) which can measure the laser BN frequency to within an accuracy of 0.22 uHz. The inter-space craft (SC) laser links including the time-delay due to the 5 Gm light travel time along the LISA arms, the laser Doppler shifts due to differential SC motion, and the GW induced laser phase modulations are simulated electronically using the electronic phase delay (EPD) unit. The EPD unit replicates the laser field propagation between SC by measuring a photodetector beat-note frequency with the UF-phasemeter and storing the information in memory. After the requested delay time, the frequency information is added to a Doppler offset and a GW-like frequency modulation. The signal is then regenerated with the inter-SC laser phase affects applied. Utilizing these components, I will present the first complete TDI simulations performed using the UFLIS. The LISA model is presented along-side the simulation, comparing the generation and measurement of LISA-like signals. Phasemeter measurements are used in post-processing and combined in the linear combinations defined by TDI, thus, canceling the laser phase and phase-lock loop noise to extract the applied GW modulation buried under the noise. Nine order of magnitude common mode laser noise cancellation is achieved at a frequency of 1 mHz and the GW signal is clearly visible after the laser and PLL noise cancellation.

Electrochemical impedance spectroscopy study on polymerization of L-lysine on electrode surface and its application for immobilization and detection of suspension cells.

PubMed

Huang, Baozhen; Jia, Ningming; Chen, Lina; Tan, Liang; Yao, Shouzhuo

2014-07-15

Poly-L-lysine (PLL), which has been employed as a conductive polymer in the construction of some electrochemical sensors, can be prepared using L-lysine by cyclic voltammetry (CV) with a wide potential range. However, the presented explanation and description about its polymerization mechanism seems oversimplified because the self-reaction of electrode and the electrolysis of solvent at high potential are ignored. This work presents an intensive investigation on the relevant reactions during the process of PLL-polymerization using CV, X-ray photoelectron spectroscopy, Fourier transform-infrared spectroscopy, and electrochemical impedance spectroscopy. At a higher positive potential, the transfer from lysine molecules to cation radicals and the polymerization reaction on the glassy carbon electrode (GCE) could be achieved, accompanied by the activation of GCE, the formation of oxygen-containing functional groups, and the generation of oxygen derived from the oxidation of water. The adsorbed oxygen had a seriously negative effect on the formation of PLL unless it suffered reduction at a lower negative potential. The charge transfer through the electrochemical polymerized PLL film was seriously hindered by the immobilization of suspension cells due to the electrostatic interaction. The charge-transfer resistance difference (ΔR(ct)) was increased with the enhancement of the cell number (N(cells)) and the 1/ΔR(ct) value displayed a linear response with 1/N(cells) in the range of 5.0 × 10(2)-1.0 × 10(5) cells with a detection limit of 180 cells estimated at a signal-to-noise ratio of 3. A sensitive electrochemical sensor for the quantitative detection of suspension cells was developed.

Bioinspired Star-Shaped Poly(l-lysine) Polypeptides: Efficient Polymeric Nanocarriers for the Delivery of DNA to Mesenchymal Stem Cells.

PubMed

Walsh, David P; Murphy, Robert D; Panarella, Angela; Raftery, Rosanne M; Cavanagh, Brenton; Simpson, Jeremy C; O'Brien, Fergal J; Heise, Andreas; Cryan, Sally-Ann

2018-05-07

The field of tissue engineering is increasingly recognizing that gene therapy can be employed for modulating in vivo cellular response thereby guiding tissue regeneration. However, the field lacks a versatile and biocompatible gene delivery platform capable of efficiently delivering transgenes to mesenchymal stem cells (MSCs), a cell type often refractory to transfection. Herein, we describe the extensive and systematic exploration of three architectural variations of star-shaped poly(l-lysine) polypeptide (star-PLL) with varying number and length of poly(l-lysine) arms as potential nonviral gene delivery vectors for MSCs. We demonstrate that star-PLL vectors are capable of self-assembling with pDNA to form stable, cationic nanomedicines. Utilizing high content screening, live cell imaging, and mechanistic uptake studies we confirm the intracellular delivery of pDNA by star-PLLs to MSCs is a rapid process, which likely proceeds via a clathrin-independent mechanism. We identify a star-PLL composition with 64 poly(l-lysine) arms and five l-lysine subunits per arm as a particularly efficient vector that is capable of delivering both reporter genes and the therapeutic transgenes bone morphogenetic protein-2 and vascular endothelial growth factor to MSCs. This composition facilitated a 1000-fold increase in transgene expression in MSCs compared to its linear analogue, linear poly(l-lysine). Furthermore, it demonstrated comparable transgene expression to the widely used vector polyethylenimine using a lower pDNA dose with significantly less cytotoxicity. Overall, this study illustrates the ability of the star-PLL vectors to facilitate efficient, nontoxic nucleic acid delivery to MSCs thereby functioning as an innovative nanomedicine platform for tissue engineering applications.

Preconditioning methods influence tumor property in an orthotopic bladder urothelial carcinoma rat model

PubMed Central

MIYAZAKI, KOZO; MORIMOTO, YUJI; NISHIYAMA, NOBUHIRO; SATOH, HIROYUKI; TANAKA, MASAMITSU; SHINOMIYA, NARIYOSHI; ITO, KEIICHI

2014-01-01

Urothelial carcinoma (UC) is an extremely common type of cancer that occurs in the bladder. It has a particularly high rate of recurrence. Therefore, preclinical studies using animal models are essential to determine effective forms of treatment. In the present study, in order to establish an orthotopic bladder UC animal model with clinical relevance, the effects of preconditioning methods on properties of the developed tumor were evaluated. The bladder cavity was pretreated with phosphate-buffered saline (PBS), acid-base, trypsin (TRY) or poly (L-lysine) (PLL) and then rat UC cells (AY-27) (4×106 cells) were inoculated. The results demonstrated that, two weeks later, the tumorigenic rate (88%) and tumor count (2.3 per rat) were not significantly different among the preconditioning methods, whereas tumor volume and invasion depth into bladder tissue were significantly different. Average tumor volumes were >50 mm3 in the PBS and acid-base-treated groups and <10 mm3 in the TRY- and PLL-treated groups. The percentage of invasive tumors (T2 or more advanced stage) was ∼75% of total tumors in the PBS- and acid-base-treated groups, whereas the percentages were reduced in the TRY- and PLL-treated groups (58 and 32%, respectively). Non-invasive tumors (Ta or T1) accounted for 54% of tumors in the PLL-treated group, which was 2-5-fold higher than the percentages in the remaining groups. Properties of the developed tumor in the rat orthotopic UC model were different depending on preconditioning methods. Therefore, different animal models suitable for a discrete preclinical examination may be established by using the appropriate preconditioning condition. PMID:24649309

[Marrow stromal cells cultured in N2-supplemented medium: implications on the generation of neural cells].

PubMed

Castillo-Díaz, L; de la Cuétara-Bernal, K; García-Varona, A Y

Most of the culture system for in vitro maintenance and neural differentiation of marrow stromal cells (MSCs) use synthetic media supplemented with 10 or 20% fetal bovine serum (FBS). Serum, however, is comprised of unknown quantities of undefined substances which could interfere the effect of exogenous substances on neural differentiation of MSCs. AIM. Here we describe survival of MSCs cultured in culture conditions where serum was reduced at 0.5 and 1% using Bottenstein and Sato's N2 formula (1979) and poly-L-lysine (PLL)-coated substrate. Stromal cells isolated from rat femurs were cultivated in Dulbecco's modified Eagle medium at 10, 1, 0.5% FBS or in serum free medium containing N2 formula. In serum free medium or at low serum concentration culture surface was coated with PLL. Cell survival was determined by MTT method or by counting viable cells. Survival of MSCs cultured in N2 supplement was reduced at about 40% of that observed in 10% FBS containing medium. Under these conditions cell morphology was also affected. When N2 containing medium was supplemented with FBS at 0.5 or 1% a significant increase of survival with respect to that observed in N2-supplemented cultures was observed. Cells seeded on PLL-coated surface increased their survival by contrast with their homologous cultures seeded on uncoated surface. The culture system which combines N2 formula with FBS 1% and PLL-coated surface is useful for the maintenance of MSCs. These conditions offer advantages for the study of differentiation of these cells because they reduce the confounding influence of serum. The possible implication of this culture system for the study of neural differentiation by these cells is discussed.

Simulation of Tracer Concentration Data in the Brush Creek Drainage Flow Using an Integrated Puff Model.

NASA Astrophysics Data System (ADS)

Rao, K. Shankar; Eckman, Richard M.; Hosker, Rayford P., Jr.

1989-07-01

During the 1984 ASCOT field study in Brush Creek Valley, two perfluorocarbon tracers were released into the nocturnal drainage flow at two different heights. The resulting surface concentrations were sampled at 90 sites, and vertical concentration profiles at 11 sites. These detailed tracer measurements provide a valuable dataset for developing and testing models of pollutant transport and dispersion in valleys.In this paper, we present the results of Gaussian puff model simulations of the tracer releases in Brush Creek Valley. The model was modified to account for the restricted lateral dispersion in the valley, and for the gross elevation differences between the release site and the receptors. The variable wind fields needed to transport the puffs were obtained by interpolation between wind profiles measured using tethered balloons at five along-valley sites. Direct turbulence measurements were used to estimate diffusion. Subsidence in the valley flow was included for elevated releases.Two test simulations-covering different nights, tracers, and release heights-were performed. The predicted hourly concentrations were compared with observations at 51 ground-level locations. At most sites, the predicted and observed concentrations agree within a factor of 2 to 6. For the elevated release simulation, the observed mean concentration is 40 pL/L, the predicted mean is 21 pL/L, the correlation coefficient between the observed and predicted concentrations is 0.24, and the index of agreement is 0.46. For the surface release simulation, the observed mean is 85 pL/L, and the predicted mean is 73 pL/L. The correlation coefficient is 0.23, and the index of agreement is 0.42. The results suggest that this modified puff model can be used as a practical tool for simulating pollutant transport and dispersion in deep valleys.

Unconventional Maturation of Dendritic Cells Induced by Particles from the Laminated Layer of Larval Echinococcus granulosus

PubMed Central

Casaravilla, Cecilia; Pittini, Álvaro; Rückerl, Dominik; Seoane, Paula I.; Jenkins, Stephen J.; MacDonald, Andrew S.; Ferreira, Ana M.; Allen, Judith E.

2014-01-01

The larval stage of the cestode parasite Echinococcus granulosus causes hydatid disease in humans and livestock. This infection is characterized by the growth in internal organ parenchymae of fluid-filled structures (hydatids) that elicit surprisingly little inflammation in spite of their massive size and persistence. Hydatids are protected by a millimeter-thick layer of mucin-based extracellular matrix, termed the laminated layer (LL), which is thought to be a major factor determining the host response to the infection. Host cells can interact both with the LL surface and with materials that are shed from it to allow parasite growth. In this work, we analyzed the response of dendritic cells (DCs) to microscopic pieces of the native mucin-based gel of the LL (pLL). In vitro, this material induced an unusual activation state characterized by upregulation of CD86 without concomitant upregulation of CD40 or secretion of cytokines (interleukin 12 [IL-12], IL-10, tumor necrosis factor alpha [TNF-α], and IL-6). When added to Toll-like receptor (TLR) agonists, pLL-potentiated CD86 upregulation and IL-10 secretion while inhibiting CD40 upregulation and IL-12 secretion. In vivo, pLL also caused upregulation of CD86 and inhibited CD40 upregulation in DCs. Contrary to expectations, oxidation of the mucin glycans in pLL with periodate did not abrogate the effects on cells. Reduction of disulfide bonds, which are known to be important for LL structure, strongly diminished the impact of pLL on DCs without altering the particulate nature of the material. In summary, DCs respond to the LL mucin meshwork with a “semimature” activation phenotype, both in vitro and in vivo. PMID:24842926

Patient-Customized Drug Combination Prediction and Testing for T-cell Prolymphocytic Leukemia Patients.

PubMed

He, Liye; Tang, Jing; Andersson, Emma I; Timonen, Sanna; Koschmieder, Steffen; Wennerberg, Krister; Mustjoki, Satu; Aittokallio, Tero

2018-05-01

The molecular pathways that drive cancer progression and treatment resistance are highly redundant and variable between individual patients with the same cancer type. To tackle this complex rewiring of pathway cross-talk, personalized combination treatments targeting multiple cancer growth and survival pathways are required. Here we implemented a computational-experimental drug combination prediction and testing (DCPT) platform for efficient in silico prioritization and ex vivo testing in patient-derived samples to identify customized synergistic combinations for individual cancer patients. DCPT used drug-target interaction networks to traverse the massive combinatorial search spaces among 218 compounds (a total of 23,653 pairwise combinations) and identified cancer-selective synergies by using differential single-compound sensitivity profiles between patient cells and healthy controls, hence reducing the likelihood of toxic combination effects. A polypharmacology-based machine learning modeling and network visualization made use of baseline genomic and molecular profiles to guide patient-specific combination testing and clinical translation phases. Using T-cell prolymphocytic leukemia (T-PLL) as a first case study, we show how the DCPT platform successfully predicted distinct synergistic combinations for each of the three T-PLL patients, each presenting with different resistance patterns and synergy mechanisms. In total, 10 of 24 (42%) of selective combination predictions were experimentally confirmed to show synergy in patient-derived samples ex vivo The identified selective synergies among approved drugs, including tacrolimus and temsirolimus combined with BCL-2 inhibitor venetoclax, may offer novel drug repurposing opportunities for treating T-PLL. Significance: An integrated use of functional drug screening combined with genomic and molecular profiling enables patient-customized prediction and testing of drug combination synergies for T-PLL patients. Cancer Res; 78(9); 2407-18. ©2018 AACR . ©2018 American Association for Cancer Research.

Combined use of leptin and mechanical stress has osteogenic effects on ossification of the posterior longitudinal ligament.

PubMed

Chen, Shuai; Zhu, Haifeng; Wang, Gangliang; Xie, Ziang; Wang, Jiying; Chen, Jian

2018-06-16

To evaluate the effects of leptin/leptin receptor (LepR) combined with mechanical stress on the development of ossification of the posterior longitudinal ligament (OPLL), which is a disease characterized by ectopic bone formation of the posterior longitudinal ligament (PLL) and can lead to radiculopathy and myelopathy. Six human samples of the PLL were analyzed for the expression of leptin and LepR by RT-PCR and western blotting. PLL cells were stimulated with leptin and mechanical stress delivered via a Flexcell tension system, and osteogenic differentiation was evaluated by RT-PCR and western blotting analysis of osteogenic marker expression as well as by alkaline phosphatase (ALP) staining and alizarin red S staining. Activation of mitogen-activated protein kinase (MAPK), Janus kinase (JAK) 2-signal transducer, activator of transcription (STAT) 3 and phosphatidylinositol 3-kinase (PI3K)-Akt was evaluated by western blotting. Samples from the OPLL group had higher LepR mRNA and protein levels and lower leptin levels than those from healthy controls. Exposure to leptin and Flexcell increased the number of ALP-positive cells and calcium nodules in a dose-dependent manner; this effect was accompanied by upregulation of the osteogenic markers osteocalcin, runt-related transcription factor 2 (RUNX2) and osteopontin. Extracellular signal-regulated kinase, P38 MAPK, JAK2, STAT3, PI3K and Akt signaling, was also activated by the combined effects of leptin and mechanical stress. Leptin and LepR are differentially expressed in OPLL tissues, and the combined use of leptin/LepR and mechanical stress promotes osteogenic differentiation of PLL cells via MAPK, JAK2-STAT3 and PI3K/Akt signaling. These slides can be retrieved under Electronic Supplementary Material.

A power scalable PLL frequency synthesizer for high-speed Δ—Σ ADC

NASA Astrophysics Data System (ADS)

Siyang, Han; Baoyong, Chi; Xinwang, Zhang; Zhihua, Wang

2014-08-01

A 35-130 MHz/300-360 MHz phase-locked loop frequency synthesizer for Δ—Σ analog-to-digital converter (ADC) in 65 nm CMOS is presented. The frequency synthesizer can work in low phase-noise mode (300-360 MHz) or in low-power mode (35-130 MHz) to satisfy the ADC's requirements. To switch between these two modes, a high frequency GHz LC VCO followed by a divided-by-four frequency divider and a low frequency ring VCO followed by a divided-by-two frequency divider are integrated on-chip. The measured results show that the frequency synthesizer achieves a phase-noise of -132 dBc/Hz at 1 MHz offset and an integrated RMS jitter of 1.12 ps with 1.74 mW power consumption from a 1.2 V power supply in low phase-noise mode. In low-power mode, the frequency synthesizer achieves a phase-noise of -112 dBc/Hz at 1 MHz offset and an integrated RMS jitter of 7.23 ps with 0.92 mW power consumption from a 1.2 V power supply.

PLL Based Energy Efficient PV System with Fuzzy Logic Based Power Tracker for Smart Grid Applications.

PubMed

Rohini, G; Jamuna, V

This work aims at improving the dynamic performance of the available photovoltaic (PV) system and maximizing the power obtained from it by the use of cascaded converters with intelligent control techniques. Fuzzy logic based maximum power point technique is embedded on the first conversion stage to obtain the maximum power from the available PV array. The cascading of second converter is needed to maintain the terminal voltage at grid potential. The soft-switching region of three-stage converter is increased with the proposed phase-locked loop based control strategy. The proposed strategy leads to reduction in the ripple content, rating of components, and switching losses. The PV array is mathematically modeled and the system is simulated and the results are analyzed. The performance of the system is compared with the existing maximum power point tracking algorithms. The authors have endeavored to accomplish maximum power and improved reliability for the same insolation of the PV system. Hardware results of the system are also discussed to prove the validity of the simulation results.

PLL Based Energy Efficient PV System with Fuzzy Logic Based Power Tracker for Smart Grid Applications

PubMed Central

Rohini, G.; Jamuna, V.

2016-01-01

This work aims at improving the dynamic performance of the available photovoltaic (PV) system and maximizing the power obtained from it by the use of cascaded converters with intelligent control techniques. Fuzzy logic based maximum power point technique is embedded on the first conversion stage to obtain the maximum power from the available PV array. The cascading of second converter is needed to maintain the terminal voltage at grid potential. The soft-switching region of three-stage converter is increased with the proposed phase-locked loop based control strategy. The proposed strategy leads to reduction in the ripple content, rating of components, and switching losses. The PV array is mathematically modeled and the system is simulated and the results are analyzed. The performance of the system is compared with the existing maximum power point tracking algorithms. The authors have endeavored to accomplish maximum power and improved reliability for the same insolation of the PV system. Hardware results of the system are also discussed to prove the validity of the simulation results. PMID:27294189

A 1.2 Gb/s Data Transmission Unit in CMOS 0.18 μm technology for the ALICE Inner Tracking System front-end ASIC

NASA Astrophysics Data System (ADS)

Mazza, G.; Aglieri Rinella, G.; Benotto, F.; Corrales Morales, Y.; Kugathasan, T.; Lattuca, A.; Lupi, M.; Ravasenga, I.

2017-02-01

The upgrade of the ALICE Inner Tracking System is based on a Monolithic Active Pixel Sensor and ASIC designed in a CMOS 0.18 μ m process. In order to provide the required output bandwidth (1.2 Gb/s for the inner layers and 400 Mb/s for the outer ones) on a single high speed serial link, a custom Data Transmission Unit (DTU) has been developed in the same process. The DTU includes a clock multiplier PLL, a double data rate serializer and a pseudo-LVDS driver with pre-emphasis and is designed to be SEU tolerant.

The feasibility of using magnetic nanoparticles modified as gene vector.

PubMed

Chen, D; Tang, Q; Xue, W; Wang, X

2010-06-01

To evaluate the feasibility of using magnetic nanoparticles (MNPs) as gene vector and the effect of magnetic field on efficiency of transfection. Magnetic nanoparticles were prepared by controlling some chemical reaction parameters through a partially reduction precipitation method with ferric chloride aqueous solution as precursor material. The surface of particles was modified by polyethyleneimine (PEI) agents. The appearance, the size distribution, structure and phase constitute of MNPs were characterized by Transmission electron microscope (TEM), X-ray diffraction (XRD); the potential of absorbing DNA of MNPs was analysed by electrophoresis. Transfection was determined by delivering reporter gene, PGL2-control encoding luciferase, to different cell lines using MNPs-PLL as vector. The effect of magnetic field on the efficiency of transfection was determined using Nd-Fe-B permanent magnet. Foreign gene could be delivered to various cell lines by MNPs-PLL and expressed with high efficiency but the transfection efficiency and time course varied in the different cell lines studied. Magnetic field could enhance the efficiency of transfection by 5-10 fold. MNPs- PLL can be used as a novel non-viral gene vector in vitro, which offers a basis for gene delivery in vivo.

[Building immune microsphere against tumor necrosis factor-alpha (TNF-alpha)].

PubMed

Wang, Qin; Wu, Xiongfei; Wang, Junxia; Liu, Hong; Li, Lian; Jin, Xiyu

2005-12-01

We have constructed the immune microsphere against tumor necrosis factor-alpha (TNF-alpha) prospectively, hoping to establish the experiment groundwork in more researches which could be used in specific elimination of the TNF-alpha by blood purification method for the future. The recombinant human tumor necrosis factor-alpha monoclonal antibody (rHTNF-alpha McAb) was wrapped on the polystyrene microsphere (PSM) carrier connecting poly-L-lysine (PLL) beforehand. They were earmarked by the fluorescein isothiocyanate (FITC) respectively. The packing conditions were examined using the inversted and fluorescence microscopes and the spectrophotometer. The results showed that the best conditions for wrapping were 20 degrees C, pH9.5 and 60 minutes. The PLL content was not changed in the washing fluid after coating, which indicated the wrapping was quite firm. At the same temperature and same coating time, the rHTNF-alpha McAb coated on the PLL was obviously substantial when the concentration of glutaraldehyde solution was 0.2%. The findings demonstrated that the built immune microsphers can be used as a novel adsorption material. This method is simple and economic, and it offers a new approach to the related studies.

Evaluation of Thermostabilities of Enzymes, Mediators and Immobilizing Membranes for Enzyme Sensors

NASA Astrophysics Data System (ADS)

Yamada, Yohei; Ohnishi, Yuki; Hayashi, Tetsuya; Isobe, Yoshifumi; Yabutani, Tomoki

The stability of the constituents of electrochemical measurement, electron mediators, enzymes and enzyme-immobilizing membranes was evaluated under high temperature (maximum 75°C) by electrochemical analysis, UV-Vis spectrometry (UV-Vis) and UV circular dichroism (CD). As a result of stability evaluation of mediators at 75°C, electrochemical activity of 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid ammonium salt (ABTS), potassium ferricyanide (K3[Fe(CN)6]) and ferrocenemethanol (FcOH) were not changed, but 2,6-dichloroindophenol (DCIP), p-benzoquinone (p-BQ), vitaminK3 (VK3) were greatly decreased. The stability of diaphorase from Bacillus stearothermophilus (DI) were compared between in-solution and in several types of membranes, Agarose H, Poly-L-lysine (PLL) and poly-ion-complex (PIC) by electrochemical analysis. In solution, activity and secondary structure of DI were changed at 65°C or higher. This tendency of activity was not much different in Agarose H but in PLL, the activity was almost kept until 70°C. It was suggested that DI was fixed on the electrodes in high concentration and the elimination of DI seldom arise in PLL from the magnitude of the current response and the results of prolonged stability evaluation.

Versatile all-digital time interval measuring system

NASA Astrophysics Data System (ADS)

Vyhlidal, David; Cech, Miroslav

2011-06-01

This paper describes a design and performance of a versatile all-digital time interval measuring system. The measurement method is based on an interpolation principle. In this principle the time interval is first roughly digitized by a coarse counter driven by a high stability reference clock and the fractions between the clock periods are measured by two Time-to-Digital Converter chips TDC-GPX manufactured by Acam messelectronic. Control circuits allow programmable customization of the system to satisfy many applications such as laser range finding, event counting, or time-of-flight measurements in various physics experiments. The system has two reference clocks inputs and two independent channels for measuring start and stop events. Only one 40 MHz reference is required for the measurement. The second reference can be, for example, 1 PPS (Pulse per Second) signal from a GPS (Global Positioning System) to time tag events. Time intervals are measured using the highest resolution mode of the TDC-GPX chips. The resolution of each chip is software programmable and is PLL (Phase Locked Loop) stabilized against temperature and voltage variations. The system can achieve a timing resolution better than 15 ps rms with up to 90 kHz repetition rate. The time interval measurement range is from 0 ps up to 1 second. The power consumption of the whole system is 18 W including an embedded computer board and an LCD (Liquid Crystal Display) screen. The embedded computer controls the whole system, collects and evaluates measurement data and with the display provides a user interface. The system is implemented using commercially available components.

Joint Carrier-Phase Synchronization and LDPC Decoding

NASA Technical Reports Server (NTRS)

Simon, Marvin; Valles, Esteban

2009-01-01

A method has been proposed to increase the degree of synchronization of a radio receiver with the phase of a suppressed carrier signal modulated with a binary- phase-shift-keying (BPSK) or quaternary- phase-shift-keying (QPSK) signal representing a low-density parity-check (LDPC) code. This method is an extended version of the method described in Using LDPC Code Constraints to Aid Recovery of Symbol Timing (NPO-43112), NASA Tech Briefs, Vol. 32, No. 10 (October 2008), page 54. Both methods and the receiver architectures in which they would be implemented belong to a class of timing- recovery methods and corresponding receiver architectures characterized as pilotless in that they do not require transmission and reception of pilot signals. The proposed method calls for the use of what is known in the art as soft decision feedback to remove the modulation from a replica of the incoming signal prior to feeding this replica to a phase-locked loop (PLL) or other carrier-tracking stage in the receiver. Soft decision feedback refers to suitably processed versions of intermediate results of iterative computations involved in the LDPC decoding process. Unlike a related prior method in which hard decision feedback (the final sequence of decoded symbols) is used to remove the modulation, the proposed method does not require estimation of the decoder error probability. In a basic digital implementation of the proposed method, the incoming signal (having carrier phase theta theta (sub c) plus noise would first be converted to inphase (I) and quadrature (Q) baseband signals by mixing it with I and Q signals at the carrier frequency [wc/(2 pi)] generated by a local oscillator. The resulting demodulated signals would be processed through one-symbol-period integrate and- dump filters, the outputs of which would be sampled and held, then multiplied by a soft-decision version of the baseband modulated signal. The resulting I and Q products consist of terms proportional to the cosine and sine of the carrier phase cc as well as correlated noise components. These products would be fed as inputs to a digital PLL that would include a number-controlled oscillator (NCO), which provides an estimate of the carrier phase, theta(sub c).

Hidden Attractors in Dynamical Systems. From Hidden Oscillations in Hilbert-Kolmogorov Aizerman, and Kalman Problems to Hidden Chaotic Attractor in Chua Circuits

NASA Astrophysics Data System (ADS)

Leonov, G. A.; Kuznetsov, N. V.

From a computational point of view, in nonlinear dynamical systems, attractors can be regarded as self-excited and hidden attractors. Self-excited attractors can be localized numerically by a standard computational procedure, in which after a transient process a trajectory, starting from a point of unstable manifold in a neighborhood of equilibrium, reaches a state of oscillation, therefore one can easily identify it. In contrast, for a hidden attractor, a basin of attraction does not intersect with small neighborhoods of equilibria. While classical attractors are self-excited, attractors can therefore be obtained numerically by the standard computational procedure. For localization of hidden attractors it is necessary to develop special procedures, since there are no similar transient processes leading to such attractors. At first, the problem of investigating hidden oscillations arose in the second part of Hilbert's 16th problem (1900). The first nontrivial results were obtained in Bautin's works, which were devoted to constructing nested limit cycles in quadratic systems, that showed the necessity of studying hidden oscillations for solving this problem. Later, the problem of analyzing hidden oscillations arose from engineering problems in automatic control. In the 50-60s of the last century, the investigations of widely known Markus-Yamabe's, Aizerman's, and Kalman's conjectures on absolute stability have led to the finding of hidden oscillations in automatic control systems with a unique stable stationary point. In 1961, Gubar revealed a gap in Kapranov's work on phase locked-loops (PLL) and showed the possibility of the existence of hidden oscillations in PLL. At the end of the last century, the difficulties in analyzing hidden oscillations arose in simulations of drilling systems and aircraft's control systems (anti-windup) which caused crashes. Further investigations on hidden oscillations were greatly encouraged by the present authors' discovery, in 2010 (for the first time), of chaotic hidden attractor in Chua's circuit. This survey is dedicated to efficient analytical-numerical methods for the study of hidden oscillations. Here, an attempt is made to reflect the current trends in the synthesis of analytical and numerical methods.

Resonant Acoustic Measurement of Vapor Phase Transport Phenomenon

NASA Astrophysics Data System (ADS)

Schuhmann, R. J.; Garrett, S. L.; Matson, J. V.

2002-12-01

A major impediment to accurate non steady-state diffusion measurements is the ability to accurately measure and track a rapidly changing gas concentration without disturbing the system. Non-destructive methods that do not interfere with system dynamics have been developed in the past. These methods, however, have tended to be cumbersome or inaccurate at low concentrations. A new experimental approach has been developed to measure gaseous diffusion in free air and through porous materials. The method combines the traditional non steady-state laboratory methodology with resonant acoustic gas analysis. A phase-locked-loop (PLL) resonance frequency tracker is combined with a thermally insulated copper resonator. A piston sealed with a metal bellows excites the fundamental standing wave resonance of the resonator. The PLL maintains a constant phase difference (typically 90§) between the accelerometer mounted on the piston and a microphone near the piston to track the resonance frequency in real time. A capillary or glass bead filled core is fitted into an o-ring sealed opening at the end of the resonator opposite the bellows. The rate at which the tracer gas is replaced by air within the resonator is controlled by the diffusion coefficient of the gas in free air through the capillary (DA) or by the effective diffusion coefficient of the gas through the core (De). The mean molecular weight of the gas mixture in the resonator is directly determined six times each minute from the ratio of the absolute temperature to the square of the fundamental acoustic resonance frequency. Average system stability (temperature divided by frequency squared) is better than 350 ppm. DA values for a 0.3-inch diameter capillary were in excellent agreement with published values. De values for porous media samples (0.5 mm glass beads) of four different lengths (1 through 4 inches) using three different tracer gases (He, CH4, Kr) will be reported. Comments will be offered regarding tracer gas selection and device orientation and their effect on experimental results. [Work supported by the Office of Naval Research.

Guiding neuron development with planar surface gradients of substrate cues deposited using microfluidic devices.

PubMed

Millet, Larry J; Stewart, Matthew E; Nuzzo, Ralph G; Gillette, Martha U

2010-06-21

Wiring the nervous system relies on the interplay of intrinsic and extrinsic signaling molecules that control neurite extension, neuronal polarity, process maturation and experience-dependent refinement. Extrinsic signals establish and enrich neuron-neuron interactions during development. Understanding how such extrinsic cues direct neurons to establish neural connections in vitro will facilitate the development of organized neural networks for investigating the development and function of nervous system networks. Producing ordered networks of neurons with defined connectivity in vitro presents special technical challenges because the results must be compliant with the biological requirements of rewiring neural networks. Here we demonstrate the ability to form stable, instructive surface-bound gradients of laminin that guide postnatal hippocampal neuron development in vitro. Our work uses a three-channel, interconnected microfluidic device that permits the production of adlayers of planar substrates through the combination of laminar flow, diffusion and physisorption. Through simple flow modifications, a variety of patterns and gradients of laminin (LN) and fluorescein isothiocyanate-conjugated poly-l-lysine (FITC-PLL) were deposited to present neurons with an instructive substratum to guide neuronal development. We present three variations in substrate design that produce distinct growth regimens for postnatal neurons in dispersed cell cultures. In the first approach, diffusion-mediated gradients of LN were formed on cover slips to guide neurons toward increasing LN concentrations. In the second approach, a combined gradient of LN and FITC-PLL was produced using aspiration-driven laminar flow to restrict neuronal growth to a 15 microm wide growth zone at the center of the two superimposed gradients. The last approach demonstrates the capacity to combine binary lines of FITC-PLL in conjunction with surface gradients of LN and bovine serum albumin (BSA) to produce substrate adlayers that provide additional levels of control over growth. This work demonstrates the advantages of spatio-temporal fluid control for patterning surface-bound gradients using a simple microfluidics-based substrate deposition procedure. We anticipate that this microfluidics-based patterning approach will provide instructive patterns and surface-bound gradients to enable a new level of control in guiding neuron development and network formation.

PECTATE LYASE-LIKE 9 from Brassica campestris is associated with intine formation.

PubMed

Jiang, Jingjing; Yao, Lina; Yu, Youjian; Liang, Ying; Jiang, Jianxia; Ye, Nenghui; Miao, Ying; Cao, Jiashu

2014-12-01

Brassica campestris pectate lyase-like 9 (BcPLL9) was previously identified as a differentially expressed gene both in buds during late pollen developmental stage and in pistils during fertilization in Chinese cabbage. To characterize the gene's function, antisense-RNA lines of BcPLL9 (bcpll9) were constructed in Chinese cabbage. Self- and cross-fertilization experiments harvested half seed yields when bcpll9 lines were used as pollen donors. In vivo and in vitro pollen germination assays showed that nearly half of the pollen tubes in bcpll9 were irregular with shorter length and uneven surface. Aniline blue staining identified abnormal accumulation of a specific bright blue unknown material in the bcpll9 pollen portion. Scanning electron microscopy observation verified the abnormal outthrust material to be near the pollen germinal furrows. Transmission electron microscopy observation revealed the internal endintine layer was overdeveloped and predominantly occupied the intine. This abnormally formed intine likely induced the wavy structure and growth arrest of the pollen tube in half of the bcpll9 pollen grains, which resulted in less seed yields. Collectively, this study presented a novel PLL gene that has an important function in B. campestris intine formation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Ionic Driven Embedment of Hyaluronic Acid Coated Liposomes in Polyelectrolyte Multilayer Films for Local Therapeutic Delivery

NASA Astrophysics Data System (ADS)

Hayward, Stephen L.; Francis, David M.; Sis, Matthew J.; Kidambi, Srivatsan

2015-10-01

The ability to control the spatial distribution and temporal release of a therapeutic remains a central challenge for biomedical research. Here, we report the development and optimization of a novel substrate mediated therapeutic delivery system comprising of hyaluronic acid covalently functionalized liposomes (HALNPs) embedded into polyelectrolyte multilayer (PEM) platform via ionic stabilization. The PEM platform was constructed from sequential deposition of Poly-L-Lysine (PLL) and Poly(Sodium styrene sulfonate) (SPS) “(PLL/SPS)4.5” followed by adsorption of anionic HALNPs. An adsorption affinity assay and saturation curve illustrated the preferential HALNP deposition density for precise therapeutic loading. (PLL/SPS)2.5 capping layer on top of the deposited HALNP monolayer further facilitated complete nanoparticle immobilization, cell adhesion, and provided nanoparticle confinement for controlled linear release profiles of the nanocarrier and encapsulated cargo. To our knowledge, this is the first study to demonstrate the successful embedment of a translatable lipid based nanocarrier into a substrate that allows for temporal and spatial release of both hydrophobic and hydrophilic drugs. Specifically, we have utilized our platform to deliver chemotherapeutic drug Doxorubicin from PEM confined HALNPs. Overall, we believe the development of our HALNP embedded PEM system is significant and will catalyze the usage of substrate mediated delivery platforms in biomedical applications.

Characterization of two strains of selectively bred guinea-pigs. 2. Differences in immune response to synthetic polypeptides.

PubMed

Lundberg, L; Koch, C; Magnusson, M; Bertelsen, C

1983-06-01

Two strains of guinea-pigs selectively bred for either high (IMM/S) or low (IMM/R) responsiveness to ovalbumin-induced respiratory anaphylaxis were examined for their immune response to a copolymer of L-glutamic acid and L-alanine (GA), a copolymer of L-glutamic acid and L-tyrosine (GT), and to a dinitro-phenyl derivative of a homopolymer of L-lysine (DNP-PLL). Considerable differences between the strains in development of cellular hypersensitivity and in the production of antibodies were observed. Guinea-pigs from IMM/S were all responders to GA and DNP-PLL and non-responders to GT, while guinea-pigs from two of three lines from IMM/R were responders to GT and non-responders to GA and DNP-PLL. The third IMM/R line showed an immune response pattern similar to guinea-pigs of strain IMM/S. Preliminary breeding studies confirmed that the immune response to these three antigens is under the control of dominant autosomal genes, since (IMM/S x IMM/R) F1 animals responded to all three antigens. It is concluded that these three antigens may serve as immune response markers in genetic studies of the differences between guinea-pigs from IMM/S and IMM/R in their ability to develop respiratory anaphylaxis.

SALT, a dedicated readout chip for high precision tracking silicon strip detectors at the LHCb Upgrade

NASA Astrophysics Data System (ADS)

Bugiel, Sz.; Dasgupta, R.; Firlej, M.; Fiutowski, T.; Idzik, M.; Kuczynska, M.; Moron, J.; Swientek, K.; Szumlak, T.

2016-02-01

The Upstream Tracker (UT) silicon strip detector, one of the central parts of the tracker system of the modernised LHCb experiment, will use a new 128-channel readout ASIC called SALT. It will extract and digitise analogue signals from the UT sensors, perform digital signal processing and transmit a serial output data. The SALT is being designed in CMOS 130 nm process and uses a novel architecture comprising of analog front-end and fast (40 MSps) ultra-low power (<0.5 mW) 6-bit ADC in each channel. The prototype ASICs of important functional blocks, like analogue front-end, 6-bit SAR ADC, PLL, and DLL, were designed, fabricated and tested. A prototype of an 8-channel version of the SALT chip, comprising all important functionalities was also designed and fabricated. The architecture and design of the SALT, together with the selected preliminary tests results, are presented.

Optimum design of hybrid phase locked loops

NASA Technical Reports Server (NTRS)

Lee, P.; Yan, T.

1981-01-01

The design procedure of phase locked loops is described in which the analog loop filter is replaced by a digital computer. Specific design curves are given for the step and ramp input changes in phase. It is shown that the designed digital filter depends explicitly on the product of the sampling time and the noise bandwidth of the phase locked loop. This technique of optimization can be applied to the design of digital analog loops for other applications.

Implantable control, telemetry, and solar energy system in the moving actuator type total artificial heart.

PubMed

Ahn, J M; Lee, J H; Choi, S W; Kim, W E; Omn, K S; Park, S K; Kim, W G; Roh, J R; Min, B G

1998-03-01

The moving actuator type total artificial heart (TAH) developed in the Seoul National University has numerous design improvements based upon the digital signal processor (DSP). These improvements include the implantability of all electronics, an automatic control algorithm, and extension of the battery run-time in connection with an amorphous silicon solar system (SS). The implantable electronics consist of the motor drive, main processor, intelligent Li ion battery management (LIBM) based upon the DSP, telemetry system, and transcutaneous energy transmission (TET) system. Major changes in the implantable electronics include decreasing the temperature rise by over 21 degrees C on the motor drive, volume reduction (40 x 55 x 33 mm, 7 cell assembly) of the battery pack using a Li ion (3.6 V/cell, 900 mA.h), and improvement of the battery run-time (over 40 min) while providing the cardiac output (CO) of 5 L/min at 100 mm Hg afterload when the external battery for testing is connected with the SS (2.5 W, 192.192, 1 kg) for the external battery recharge or the partial TAH drive. The phase locked loop (PLL) based telemetry system was implemented to improve stability and the error correction DSP algorithm programmed to achieve high accuracy. A field focused light emitting diode (LED) was used to obtain low light scattering along the propagation path, similar to the optical property of the laser and miniature sized, mounted on the pancake type TET coils. The TET operating resonance frequency was self tuned in a range of 360 to 410 kHz to provide enough power even at high afterloads. An automatic cardiac output regulation algorithm was developed based on interventricular pressure analysis and carried out in several animal experiments successfully. All electronics have been evaluated in vitro and in vivo and prepared for implantation of the TAH. Substantial progress has been made in designing a completely implantable TAH at the preclinical stage.

Advanced technology satellite demodulator development

NASA Technical Reports Server (NTRS)

Ames, Stephen A.

1989-01-01

Ford Aerospace has developed a proof-of-concept satellite 8 phase shift keying (PSK) modulation and coding system operating in the Time Division Multiple Access (TDMA) mode at a data range of 200 Mbps using rate 5/6 forward error correction coding. The 80 Msps 8 PSK modem was developed in a mostly digital form and is amenable to an ASIC realization in the next phase of development. The codec was developed as a paper design only. The power efficiency goal was to be within 2 dB of theoretical at a bit error rate (BER) of 5x10(exp 7) while the measured implementation loss was 4.5 dB. The bandwidth efficiency goal was 2 bits/sec/Hz while the realized bandwidth efficiency was 1.8 bits/sec/Hz. The burst format used a preamble of only 40 8 PSK symbol times including 32 symbols of all zeros and an eight symbol unique word. The modem and associated special test equipment (STE) were fabricated mostly on a specially designed stitch-weld board although a few of the highest rate circuits were built on printed circuit cards. All the digital circuits were ECL to support the clock rates of from 80 MHz to 360 MHz. The transmitter and receiver matched filters were square-root Nyquist bandpass filters realized at the 3.37 GHz i.f. The modem operated as a coherent system although no analog phase locked (PLL) loop was employed. Within the budgetary constraints of the program, the approach to the demodulator has been proven and is eligible to proceed to the next phase of development of a satellite demodulator engineering model. This would entail the development of an ASIC version of the digital portion of the demodulator, and MMIC version of the quadrature detector, and SAW Nyquist filters to realize the bandwidth efficiency.

Radiation pressure excitation of a low temperature atomic force/magnetic force microscope for imaging in 4-300 K temperature range

NASA Astrophysics Data System (ADS)

Ćelik, Ümit; Karcı, Özgür; Uysallı, Yiǧit; Özer, H. Özgür; Oral, Ahmet

2017-01-01

We describe a novel radiation pressure based cantilever excitation method for imaging in dynamic mode atomic force microscopy (AFM) for the first time. Piezo-excitation is the most common method for cantilever excitation, however it may cause spurious resonance peaks. Therefore, the direct excitation of the cantilever plays a crucial role in AFM imaging. A fiber optic interferometer with a 1310 nm laser was used both for the excitation of the cantilever at the resonance and the deflection measurement of the cantilever in a commercial low temperature atomic force microscope/magnetic force microscope (AFM/MFM) from NanoMagnetics Instruments. The laser power was modulated at the cantilever's resonance frequency by a digital Phase Locked Loop (PLL). The laser beam is typically modulated by ˜500 μW, and ˜141.8 nmpp oscillation amplitude is obtained in moderate vacuum levels between 4 and 300 K. We have demonstrated the performance of the radiation pressure excitation in AFM/MFM by imaging atomic steps in graphite, magnetic domains in CoPt multilayers between 4 and 300 K and Abrikosov vortex lattice in BSCCO(2212) single crystal at 4 K for the first time.

Modulation format identification aided hitless flexible coherent transceiver.

PubMed

Xiang, Meng; Zhuge, Qunbi; Qiu, Meng; Zhou, Xingyu; Zhang, Fangyuan; Tang, Ming; Liu, Deming; Fu, Songnian; Plant, David V

2016-07-11

We propose a hitless flexible coherent transceiver enabled by a novel modulation format identification (MFI) scheme for dynamic agile optical networks. The modulation format transparent digital signal processing (DSP) is realized by a block-wise decision-directed least-mean-square (DD-LMS) equalizer for channel tracking, and a pilot symbol aided superscalar phase locked loop (PLL) for carrier phase estimation (CPE). For the MFI, the modulation format information is encoded onto the pilot symbols initially used for CPE. Therefore, the proposed MFI method does not require extra overhead. Moreover, it can identify arbitrary modulation formats including multi-dimensional formats, and it enables tracking of the format change for short data blocks. The performance of the proposed hitless flexible coherent transceiver is successfully evaluated with five modulation formats including QPSK, 16QAM, 64QAM, Hybrid QPSK/8QAM and set-partitioning (SP)-512-QAM. We show that the proposed MFI method induces a negligible performance penalty. Moreover, we experimentally demonstrate that such a hitless transceiver can adapt to fast block-by-block modulation format switching. Finally, the performance improvement of the proposed MFI method is experimentally verified with respect to other commonly used MFI methods.

Radiation pressure excitation of a low temperature atomic force/magnetic force microscope for imaging in 4-300 K temperature range.

PubMed

Çelik, Ümit; Karcı, Özgür; Uysallı, Yiğit; Özer, H Özgür; Oral, Ahmet

2017-01-01

We describe a novel radiation pressure based cantilever excitation method for imaging in dynamic mode atomic force microscopy (AFM) for the first time. Piezo-excitation is the most common method for cantilever excitation, however it may cause spurious resonance peaks. Therefore, the direct excitation of the cantilever plays a crucial role in AFM imaging. A fiber optic interferometer with a 1310 nm laser was used both for the excitation of the cantilever at the resonance and the deflection measurement of the cantilever in a commercial low temperature atomic force microscope/magnetic force microscope (AFM/MFM) from NanoMagnetics Instruments. The laser power was modulated at the cantilever's resonance frequency by a digital Phase Locked Loop (PLL). The laser beam is typically modulated by ∼500 μW, and ∼141.8 nm pp oscillation amplitude is obtained in moderate vacuum levels between 4 and 300 K. We have demonstrated the performance of the radiation pressure excitation in AFM/MFM by imaging atomic steps in graphite, magnetic domains in CoPt multilayers between 4 and 300 K and Abrikosov vortex lattice in BSCCO(2212) single crystal at 4 K for the first time.

Radiation pressure excitation of Low Temperature Atomic Force & Magnetic Force Microscope (LT-AFM/MFM) for Imaging

NASA Astrophysics Data System (ADS)

Karci, Ozgur; Celik, Umit; Oral, Ahmet; NanoMagnetics Instruments Ltd. Team; Middle East Tech Univ Team

2015-03-01

We describe a novel method for excitation of Atomic Force Microscope (AFM) cantilevers by means of radiation pressure for imaging in an AFM for the first time. Piezo excitation is the most common method for cantilever excitation, but it may cause spurious resonance peaks. A fiber optic interferometer with 1310 nm laser was used both to measure the deflection of cantilever and apply a force to the cantilever in a LT-AFM/MFM from NanoMagnetics Instruments. The laser power was modulated at the cantilever`s resonance frequency by a digital Phase Lock Loop (PLL). The force exerted by the radiation pressure on a perfectly reflecting surface by a laser beam of power P is F = 2P/c. We typically modulate the laser beam by ~ 800 μW and obtain 10nm oscillation amplitude with Q ~ 8,000 at 2.5x10-4 mbar. The cantilever's stiffness can be accurately calibrated by using the radiation pressure. We have demonstrated performance of the radiation pressure excitation in AFM/MFM by imaging a hard disk sample between 4-300K and Abrikosov vortex lattice in BSCCO single crystal at 4K to for the first time.

A 1024×768-12μm Digital ROIC for uncooled microbolometer FPAs

NASA Astrophysics Data System (ADS)

Eminoglu, Selim

2017-02-01

This paper reports the development of a new digital microbolometer Readout Integrated Circuit (D-ROIC), called MT10212BD. It has a format of 1024 × 768 (XGA) and a pixel pitch of 12μm. MT10212BD is Mikro Tasarim's second 12μm pitch microbolometer ROIC, which is developed specifically for surface micro machined microbolometer detector arrays with small pixel pitch using high-TCR pixel materials, such as VOx and a Si. MT10212BD has an alldigital system on-chip architecture, which generates programmable timing and biasing, and performs 14-bit analog to digital conversion (ADC). The signal processing chain in the ROIC is composed of pixel bias circuitry, integrator based programmable gain amplifier followed by column parallel ADC circuitry. MT10212BD has a serial programming interface that can be used to configure the programmable ROIC features and to load the Non-Uniformity-Correction (NUC) date to the ROIC. MT10212BD has a total of 8 high-speed serial digital video outputs, which can be programmed to operate in the 2, 4, and 8-output modes and can support frames rates above 60 fps. The high-speed serial digital outputs supports data rates as high as 400 Mega-bits/s, when operated at 50 MHz system clock frequency. There is an on-chip phase-locked-loop (PLL) based timing circuitry to generate the high speed clocks used in the ROIC. The ROIC is designed to support pixel resistance values ranging from 30KΩ to 90kΩ, with a nominal value of 60KΩ. The ROIC has a globally programmable gain in the column readout, which can be adjusted based on the detector resistance value.

Green tea polyphenol tailors cell adhesivity of RGD displaying surfaces: multicomponent models monitored optically

PubMed Central

Peter, Beatrix; Farkas, Eniko; Forgacs, Eniko; Saftics, Andras; Kovacs, Boglarka; Kurunczi, Sandor; Szekacs, Inna; Csampai, Antal; Bosze, Szilvia; Horvath, Robert

2017-01-01

The interaction of the anti-adhesive coating, poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) and its Arg-Gly-Asp (RGD) functionalized form, PLL-g-PEG-RGD, with the green tea polyphenol, epigallocatechin-gallate (EGCg) was in situ monitored. After, the kinetics of cellular adhesion on the EGCg exposed coatings were recorded in real-time. The employed plate-based waveguide biosensor is applicable to monitor small molecule binding and sensitive to sub-nanometer scale changes in cell membrane position and cell mass distribution; while detecting the signals of thousands of adhering cells. The combination of this remarkable sensitivity and throughput opens up new avenues in testing complicated models of cell-surface interactions. The systematic studies revealed that, despite the reported excellent antifouling properties of the coatings, EGCg strongly interacted with them, and affected their cell adhesivity in a concentration dependent manner. Moreover, the differences between the effects of the fresh and oxidized EGCg solutions were first demonstrated. Using a semiempirical quantumchemical method we showed that EGCg binds to the PEG chains of PLL-g-PEG-RGD and effectively blocks the RGD sites by hydrogen bonds. The calculations supported the experimental finding that the binding is stronger for the oxidative products. Our work lead to a new model of polyphenol action on cell adhesion ligand accessibility and matrix rigidity. PMID:28186133

Green tea polyphenol tailors cell adhesivity of RGD displaying surfaces: multicomponent models monitored optically.

PubMed

Peter, Beatrix; Farkas, Eniko; Forgacs, Eniko; Saftics, Andras; Kovacs, Boglarka; Kurunczi, Sandor; Szekacs, Inna; Csampai, Antal; Bosze, Szilvia; Horvath, Robert

2017-02-10

The interaction of the anti-adhesive coating, poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) and its Arg-Gly-Asp (RGD) functionalized form, PLL-g-PEG-RGD, with the green tea polyphenol, epigallocatechin-gallate (EGCg) was in situ monitored. After, the kinetics of cellular adhesion on the EGCg exposed coatings were recorded in real-time. The employed plate-based waveguide biosensor is applicable to monitor small molecule binding and sensitive to sub-nanometer scale changes in cell membrane position and cell mass distribution; while detecting the signals of thousands of adhering cells. The combination of this remarkable sensitivity and throughput opens up new avenues in testing complicated models of cell-surface interactions. The systematic studies revealed that, despite the reported excellent antifouling properties of the coatings, EGCg strongly interacted with them, and affected their cell adhesivity in a concentration dependent manner. Moreover, the differences between the effects of the fresh and oxidized EGCg solutions were first demonstrated. Using a semiempirical quantumchemical method we showed that EGCg binds to the PEG chains of PLL-g-PEG-RGD and effectively blocks the RGD sites by hydrogen bonds. The calculations supported the experimental finding that the binding is stronger for the oxidative products. Our work lead to a new model of polyphenol action on cell adhesion ligand accessibility and matrix rigidity.

PECTATE LYASE-LIKE10 is associated with pollen wall development in Brassica campestris.

PubMed

Jiang, Jingjing; Yao, Lina; Yu, Youjian; Lv, Meiling; Miao, Ying; Cao, Jiashu

2014-11-01

PECTATE LYASE-LIKE10 (PLL10) was previously identified as one of the differentially expressed genes both in microspores during the late pollen developmental stages and in pistils during the fertilization process in Chinese cabbage (Brassica campestris ssp. chinensis). Here, antisense-RNA was used to study the functions of BcPLL10 in Chinese cabbage. Abnormal pollen was identified in the transgenic lines (bcpll10-4, -5, and -6). In fertilization experiments, fewer seeds were harvested when the antisense-RNA lines were used as pollen donor. In vivo and in vitro pollen germination assays less germinated pollen tubes were observed in bcpll10 lines. Scanning electron microscopy observation verified that the tryphine materials were over accumulated around the pollen surface and sticked them together in bcpll10. Moreover, transmission electron microscopy observation revealed that the internal endintine was overdeveloped and predominantly occupied the intine, and disturbed the normal proportional distribution of the two layers in the non-germinal furrow region; and no obvious demarcation existed between them in the germinal furrow region in the bcpll10 pollen. Collectively, this study presented a novel PLL gene that played an important role during the pollen wall development in B. campestris, which may also possess potential importance for male sterility usage in agriculture. © 2014 Institute of Botany, Chinese Academy of Sciences.

Mechanical Adaptability of the MMP-Responsive Film Improves the Functionality of Endothelial Cell Monolayer.

PubMed

Hu, Mi; Chang, Hao; Zhang, He; Wang, Jing; Lei, Wen-Xi; Li, Bo-Chao; Ren, Ke-Feng; Ji, Jian

2017-07-01

Extracellular matrix and cells are inherent in coordinating and adapting to each other during all physiological and pathological processes. Synthetic materials, however, show rarely reciprocal and spatiotemporal responses to cells, and lacking self-adapting properties as well. Here, a mechanical adaptability based on the matrix metalloproteinase (MMPs) sensitive polyelectrolyte film is reported. Poly-lysine (PLL) and methacrylated hyaluronic acid (HA-MA) nanolayers are employed to build the thin film through the layer-by-layer assembly, and it is further crosslinked using MMP sensitive peptides, which endows the films with changeable mechanical properties in response to MMPs. It is demonstrated that stiffness of the (PLL/HA-MA) films increases with the crosslinking, and then decreases in response to a treatment of enzyme. Consequently, the crosslinked (PLL/HA-MA) films reveal effective growth of endothelial cells (ECs), leading to fast formation of EC monolayer. Importantly, significantly improved endothelial function of the EC monolayer, which is characterized by integrity, biomolecules release, expression of function related gene, and antithrombotic properties, is achieved along with the decrosslinking of the film because of EC-secreted MMPs. These results suggest that mechanical adaptability of substrate in Young's modulus plays a significant role in endothelial progression, which shows great application potential in tissue engineering, regenerative medicine, and organ-on-a-chip. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Immobilization of heparin/poly-(L)-lysine nanoparticles on dopamine-coated surface to create a heparin density gradient for selective direction of platelet and vascular cells behavior.

PubMed

Liu, Tao; Liu, Yang; Chen, Yuan; Liu, Shihui; Maitz, Manfred F; Wang, Xue; Zhang, Kun; Wang, Jian; Wang, Yuan; Chen, Junying; Huang, Nan

2014-05-01

Restenosis, thrombosis formation and delayed endothelium regeneration continue to be problematic for coronary artery stent therapy. To improve the hemocompatibility of the cardiovascular implants and selectively direct vascular cell behavior, a novel kind of heparin/poly-l-lysine (Hep/PLL) nanoparticle was developed and immobilized on a dopamine-coated surface. The stability and structural characteristics of the nanoparticles changed with the Hep:PLL concentration ratio. A Hep density gradient was created on a surface by immobilizing nanoparticles with various Hep:PLL ratios on a dopamine-coated surface. Antithrombin III binding quantity was significantly enhanced, and in plasma the APTT and TT times as coagulation tests were prolonged, depending on the Hep density. A low Hep density is sufficient to prevent platelet adhesion and activation. The sensitivity of vascular cells to the Hep density is very different: high Hep density inhibits the growth of all vascular cells, while low Hep density could selectively inhibit smooth muscle cell hyperplasia but promote endothelial progenitor cells and endothelial cell proliferation. These observations provide important guidance for modification of surface heparinization. We suggest that this method will provide a potential means to construct a suitable platform on a stent surface for selective direction of vascular cell behavior with low side effects. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Green tea polyphenol tailors cell adhesivity of RGD displaying surfaces: multicomponent models monitored optically

NASA Astrophysics Data System (ADS)

Peter, Beatrix; Farkas, Eniko; Forgacs, Eniko; Saftics, Andras; Kovacs, Boglarka; Kurunczi, Sandor; Szekacs, Inna; Csampai, Antal; Bosze, Szilvia; Horvath, Robert

2017-02-01

The interaction of the anti-adhesive coating, poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) and its Arg-Gly-Asp (RGD) functionalized form, PLL-g-PEG-RGD, with the green tea polyphenol, epigallocatechin-gallate (EGCg) was in situ monitored. After, the kinetics of cellular adhesion on the EGCg exposed coatings were recorded in real-time. The employed plate-based waveguide biosensor is applicable to monitor small molecule binding and sensitive to sub-nanometer scale changes in cell membrane position and cell mass distribution; while detecting the signals of thousands of adhering cells. The combination of this remarkable sensitivity and throughput opens up new avenues in testing complicated models of cell-surface interactions. The systematic studies revealed that, despite the reported excellent antifouling properties of the coatings, EGCg strongly interacted with them, and affected their cell adhesivity in a concentration dependent manner. Moreover, the differences between the effects of the fresh and oxidized EGCg solutions were first demonstrated. Using a semiempirical quantumchemical method we showed that EGCg binds to the PEG chains of PLL-g-PEG-RGD and effectively blocks the RGD sites by hydrogen bonds. The calculations supported the experimental finding that the binding is stronger for the oxidative products. Our work lead to a new model of polyphenol action on cell adhesion ligand accessibility and matrix rigidity.

Design and realization of the baseband processor in satellite navigation and positioning receiver

NASA Astrophysics Data System (ADS)

Zhang, Dawei; Hu, Xiulin; Li, Chen

2007-11-01

The content of this paper is focused on the Design and realization of the baseband processor in satellite navigation and positioning receiver. Baseband processor is the most important part of the satellite positioning receiver. The design covers baseband processor's main functions include multi-channel digital signal DDC, acquisition, code tracking, carrier tracking, demodulation, etc. The realization is based on an Altera's FPGA device, that makes the system can be improved and upgraded without modifying the hardware. It embodies the theory of software defined radio (SDR), and puts the theory of the spread spectrum into practice. This paper puts emphasis on the realization of baseband processor in FPGA. In the order of choosing chips, design entry, debugging and synthesis, the flow is presented detailedly. Additionally the paper detailed realization of Digital PLL in order to explain a method of reducing the consumption of FPGA. Finally, the paper presents the result of Synthesis. This design has been used in BD-1, BD-2 and GPS.

Influence of the foundation layer on the layer-by-layer assembly of poly-L-lysine and poly(styrenesulfonate) and its usage in the fabrication of 3D microscale features.

PubMed

Zhou, Dejian; Bruckbauer, Andreas; Batchelor, Matthew; Kang, Dae-Joon; Abell, Chris; Klenerman, David

2004-10-12

The layer-by-layer (LBL) assembly of a polypeptide, poly-L-lysine (PLL), with poly(styrenesulfonate) sodium salt (PSS) on flat template-stripped gold (TSG) surfaces precoated with a self-assembled monolayer of alkanethiols terminated with positive (pyridinium), negative (carboxylic acid), and neutral [hexa(ethylene glycol)] groups is investigated. Both the topography and the rate of film thickness growth are found to be strongly dependent on the initial surface foundation layer. LBL assembly of PLL and PSS on patterned TSG surfaces produced by micro contact printing leads to structurally distinct microscale features, including pillars, ridges, and wells, whose height can be controlled with nanometer precision. Copyright 2004 American Chemical Society

In situ crosslinked smart polypeptide nanoparticles for multistage responsive tumor-targeted drug delivery

NASA Astrophysics Data System (ADS)

Yi, Huqiang; Liu, Peng; Sheng, Nan; Gong, Ping; Ma, Yifan; Cai, Lintao

2016-03-01

Smart tumor-targeted drug delivery is crucial for improving the effect of chemotherapy and reducing the adverse effects. Here, we synthesized a smart polypeptide copolymer based on n-butylamine-poly(l-lysine)-b-poly(l-cysteine) (PLL-PLC) with functionalization of folic acid (FA) and 1,2-dicarboxylic-cyclohexene anhydride (DCA) for multistage responsive tumor-targeted drug delivery. The copolymers (FA-PLL(DCA)-PLC) spontaneously crosslinked in situ to form redox and pH dual responsive FA-PLL(DCA)-PLC nanoparticles (FD-NPs), which had a reversible zeta potential around -30 mV at pH 7.4, but switched to +15 mV at pH 5.0. Moreover, FD-NPs effectively loaded DOX with a loading capacity at 15.7 wt%. At pH 7.4, only 24.5% DOX was released within 60 h. However, at pH 5.0, the presence of 10 mM DTT dramatically accelerated DOX release with over 90% of DOX released within 10 h. Although the FD-NPs only enhanced DOX uptake in FA receptor positive (FR+) cancer cells at pH 7.4, a weak acidic condition promoted FD-NP-facilitated DOX uptake in both FR+ HeLa and FR- A549 cells, as well as significantly improving cellular binding and end/lysosomal escape. In vivo studies in a HeLa cancer model demonstrated that the charge-reversible FD-NPs delivered DOX into tumors more effectively than charge-irreversible nanoparticles. Hence, these multistage responsive FD-NPs would serve as highly efficient drug vectors for targeted cancer chemotherapy.Smart tumor-targeted drug delivery is crucial for improving the effect of chemotherapy and reducing the adverse effects. Here, we synthesized a smart polypeptide copolymer based on n-butylamine-poly(l-lysine)-b-poly(l-cysteine) (PLL-PLC) with functionalization of folic acid (FA) and 1,2-dicarboxylic-cyclohexene anhydride (DCA) for multistage responsive tumor-targeted drug delivery. The copolymers (FA-PLL(DCA)-PLC) spontaneously crosslinked in situ to form redox and pH dual responsive FA-PLL(DCA)-PLC nanoparticles (FD-NPs), which had a reversible zeta potential around -30 mV at pH 7.4, but switched to +15 mV at pH 5.0. Moreover, FD-NPs effectively loaded DOX with a loading capacity at 15.7 wt%. At pH 7.4, only 24.5% DOX was released within 60 h. However, at pH 5.0, the presence of 10 mM DTT dramatically accelerated DOX release with over 90% of DOX released within 10 h. Although the FD-NPs only enhanced DOX uptake in FA receptor positive (FR+) cancer cells at pH 7.4, a weak acidic condition promoted FD-NP-facilitated DOX uptake in both FR+ HeLa and FR- A549 cells, as well as significantly improving cellular binding and end/lysosomal escape. In vivo studies in a HeLa cancer model demonstrated that the charge-reversible FD-NPs delivered DOX into tumors more effectively than charge-irreversible nanoparticles. Hence, these multistage responsive FD-NPs would serve as highly efficient drug vectors for targeted cancer chemotherapy. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr07348k

A comparison of methods for DPLL loop filter design

NASA Technical Reports Server (NTRS)

Aguirre, S.; Hurd, W. J.; Kumar, R.; Statman, J.

1986-01-01

Four design methodologies for loop filters for a class of digital phase-locked loops (DPLLs) are presented. The first design maps an optimum analog filter into the digital domain; the second approach designs a filter that minimizes in discrete time weighted combination of the variance of the phase error due to noise and the sum square of the deterministic phase error component; the third method uses Kalman filter estimation theory to design a filter composed of a least squares fading memory estimator and a predictor. The last design relies on classical theory, including rules for the design of compensators. Linear analysis is used throughout the article to compare different designs, and includes stability, steady state performance and transient behavior of the loops. Design methodology is not critical when the loop update rate can be made high relative to loop bandwidth, as the performance approaches that of continuous time. For low update rates, however, the miminization method is significantly superior to the other methods.

Design of Test Loops for Forced Convection Heat Transfer Studies at Supercritical State

NASA Astrophysics Data System (ADS)

Balouch, Masih N.

Worldwide research is being conducted to improve the efficiency of nuclear power plants by using supercritical water (SCW) as the working fluid. One such SCW reactor considered for future development is the CANDU-Supercritical Water Reactor (CANDU-SCWR). For safe and accurate design of the CANDU-SCWR, a detailed knowledge of forced-convection heat transfer in SCW is required. For this purpose, two supercritical fluid loops, i.e. a SCW loop and an R-134a loop are developed at Carleton University. The SCW loop is designed to operate at pressures as high as 28 MPa, temperatures up to 600 °C and mass fluxes of up to 3000 kg/m2s. The R-134a loop is designed to operate at pressures as high as 6 MPa, temperatures up to 140 °C and mass fluxes in the range of 500-6000 kg/m2s. The test loops designs allow for up to 300 kW of heating power to be imparted to the fluid. Both test loops are of the closed-loop design, where flow circulation is achieved by a centrifugal pump in the SCW loop and three parallel-connected gear pumps in the R-134a loop, respectively. The test loops are pressurized using a high-pressure nitrogen cylinder and accumulator assembly, which allows independent control of the pressure, while simultaneously dampening pump induced pressure fluctuations. Heat exchangers located upstream of the pumps control the fluid temperature in the test loops. Strategically located measuring instrumentation provides information on the flow rate, pressure and temperature in the test loops. The test loops have been designed to accommodate a variety of test-section geometries, ranging from a straight circular tube to a seven-rod bundle, achieving heat fluxes up to 2.5 MW/m2 depending on the test-section geometry. The design of both test loops allows for easy reconfiguration of the test-section orientation relative to the gravitational direction. All the test sections are of the directly-heated design, where electric current passing through the pressure retaining walls of the test sections provides the Joule heating required to heat up the fluid to supercritical conditions. A high-temperature dielectric gasket isolates the current carrying parts of the test section from the rest of the assembly. Temperature and pressure drop data are collected at the inlet and outlet, and along the heated length of the test section. The test loops and test sections are designed according to American Society of Mechanical Engineers (ASME) Pressure Piping B31.1, and Boiler and Pressure Vessel Code, Section VIII-Division 1 rules. The final test loops and test sections assemblies are certified by Technical Standards and Safety Authority (TSSA). Every attempt is made to use off-the-shelf components where possible in order to streamline the design process and reduce costs. Following a rigorous selection process, stainless steel Types 316 and 316H are selected as the construction materials for the test loops, and Inconel 625 is selected as the construction material for the test sections. This thesis describes the design of the SCW and R-134a loops along with the three test-section geometries (i.e., tubular, annular and bundle designs).

A study of digital gyro compensation loops. [data conversion routines and breadboard models

NASA Technical Reports Server (NTRS)

1975-01-01

The feasibility is discussed of replacing existing state-of-the-art analog gyro compensation loops with digital computations. This was accomplished by designing appropriate compensation loops for the dry turned TDF gyro, selecting appropriate data conversion and processing techniques and algorithms, and breadboarding the design for laboratory evaluation. A breadboard design was established in which one axis of a Teledyne turned-gimbal TDF gyro was caged digitally while the other was caged using conventional analog electronics. The digital loop was designed analytically to closely resemble the analog loop in performance. The breadboard was subjected to various static and dynamic tests in order to establish the relative stability characteristics and frequency responses of the digital and analog loops. Several variations of the digital loop configuration were evaluated. The results were favorable.

Design of Digital Phase-Locked Loops For Advanced Digital Transponders

NASA Technical Reports Server (NTRS)

Nguyen, Tien M.

1994-01-01

For advanced digital space transponders, the Digital Phased-Locked Loops (DPLLs) can be designed using the available analog loops. DPLLs considered in this paper are derived from the Analog Phase-Locked Loop (APLL) using S-domain mapping techniques.

Iterative LQG Controller Design Through Closed-Loop Identification

NASA Technical Reports Server (NTRS)

Hsiao, Min-Hung; Huang, Jen-Kuang; Cox, David E.

1996-01-01

This paper presents an iterative Linear Quadratic Gaussian (LQG) controller design approach for a linear stochastic system with an uncertain open-loop model and unknown noise statistics. This approach consists of closed-loop identification and controller redesign cycles. In each cycle, the closed-loop identification method is used to identify an open-loop model and a steady-state Kalman filter gain from closed-loop input/output test data obtained by using a feedback LQG controller designed from the previous cycle. Then the identified open-loop model is used to redesign the state feedback. The state feedback and the identified Kalman filter gain are used to form an updated LQC controller for the next cycle. This iterative process continues until the updated controller converges. The proposed controller design is demonstrated by numerical simulations and experiments on a highly unstable large-gap magnetic suspension system.

Light-Triggered Release of DNA from Plasmon-Resonant Nanoparticles

NASA Astrophysics Data System (ADS)

Huschka, Ryan

Plasmon-resonant nanoparticle complexes show promising potential for lighttriggered, controllable delivery of deoxyribonucleic acids (DNA) for research and therapeutic purposes. For example, the approach of RNA interference (RNAi) . using antisense DNA or RNA oligonucleotides to silence activity of a specific pathogenic gene transcript and reduce expression of the encoded protein . is very useful in dissecting genetic function and holds promise as a molecular therapeutic. Herein, we investigate the mechanism and probe the in vitro therapeutic potential of DNA light-triggered release from plasmonic nanoparticles. First, we investigate the mechanism of light-triggered release by dehybridizing double-stranded (dsDNA) via laser illumination from two types of nanoparticle substrates: gold (Au) nanoshells and Au nanorods. Both light-triggered and thermally induced releases are distinctly observable from nanoshell-based complexes. Surprisingly, no analogous measurable light-triggered release was observable from nanorod-based complexes below the DNA melting temperature. These results suggest that a nonthermal mechanism may play a role in light-triggered DNA release. Second, we demonstrate the in vitro light-triggered release of molecules noncovalently attached within dsDNA bound to the Au nanoshell surface. DAPI (4',6- diamidino-2-phenylindole), a bright blue fluorescent molecule that binds reversibly to double-stranded DNA, was chosen to visualize this intracellular light-induced release process. Illumination through the cell membrane of the nanoshell-dsDNA-DAPI complexes dehybridizes the DNA and releases the DAPI molecules within living cells. The DAPI molecules diffuse to the nucleus and associate with the cell's endogenous DNA. This work could have future applications towards drug delivery of molecules that associate with dsDNA. Finally, we demonstrate an engineered Au nanoshell (AuNS)-based therapeutic oligonucleotide delivery vehicle, designed to release its cargo on demand upon illumination with a near-infrared (NIR) laser. A poly(L)lysine peptide (PLL) epilayer coated onto the AuNS surface (AuNS-PLL) is used to capture intact, single-stranded antisense DNA oligonucleotide, or alternatively, double-stranded short-interfering RNA (siRNA) molecules. A green fluorescent protein (GFP)-expressing human lung cancer H1299 cell line was used to determine cellular uptake and GFP gene silencing mediated by AuNS-PLL delivery vector. The light-triggered release of oligonucleotides could have broad applications in the study of cellular processes and in the development of intracellular targeted therapies.

Design and verification of wide-band, simultaneous, multi-frequency, tuning circuits for large moment transmitter loops

NASA Astrophysics Data System (ADS)

Dvorak, Steven L.; Sternberg, Ben K.; Feng, Wanjie

2017-03-01

In this paper we discuss the design and verification of wide-band, multi-frequency, tuning circuits for large-moment Transmitter (TX) loops. Since these multi-frequency, tuned-TX loops allow for the simultaneous transmission of multiple frequencies at high-current levels, they are ideally suited for frequency-domain geophysical systems that collect data while moving, such as helicopter mounted systems. Furthermore, since multi-frequency tuners use the same TX loop for all frequencies, instead of using separate tuned-TX loops for each frequency, they allow for the use of larger moment TX loops. In this paper we discuss the design and simulation of one- and three-frequency tuned TX loops and then present measurement results for a three-frequency, tuned-TX loop.

Phase-locked loops. [analog, hybrid, discrete and digital systems

NASA Technical Reports Server (NTRS)

Gupta, S. C.

1974-01-01

The basic analysis and design procedures are described for the realization of analog phase-locked loops (APLL), hybrid phase-locked loops (HPLL), discrete phase-locked loops, and digital phase-locked loops (DPLL). Basic configurations are diagrammed, and performance curves are given. A discrete communications model is derived and developed. The use of the APLL as an optimum angle demodulator and the Kalman-Bucy approach to APLL design are discussed. The literature in the area of phase-locked loops is reviewed, and an extensive bibliography is given. Although the design of APLLs is fairly well documented, work on discrete, hybrid, and digital PLLs is scattered, and more will have to be done in the future to pinpoint the formal design of DPLLs.

Specific immune response genes of new inbred strains of guinea pigs.

PubMed

Chiba, J; Egashira, Y

1978-01-01

Distribution of specific immune-response (Ir) genes controlling responsiveness to synthetic polypeptide antigens, homopolymer of poly-L-lysine (PLL), copolymer of L-glutamic acid and L-alanine (GA) and copolymer of L-glutamic acid and L-tyrosine (GT), and limiting doses of 2,4-dinitrophenyl guinea pig serum albumin (DNP-GPA) was surveyed in new inbred strains of guinea pigs, JY 1, JY 2, JY 9 and JY 10, established in this Institute. The PLL gene was not found in any of the guinea pigs. The GA gene was found in JY 1 and JY 2 guinea pigs and the GT gene in all the guinea pigs. The gene controlling responsiveness to low doses (1 microgram) of DNP-GPA was found in JY 1, JY 9 and JY 10 guinea pigs. The associated (Ia) antigens was discussed.

In situ synthesis of gold nanoparticles in exponentially-growing layer-by-layer films

PubMed Central

Shen, Liyan; Rapenne, Laetitia; Chaudouet, Patrick; Ji, Jian; Picart, Catherine

2014-01-01

In situ synthesis of inorganic nanoparticles (NPs) in polyelectrolytes multilayers (PEMs) has recently gained much attention. Due to the versatility of their composition, PEMs offer a unique opportunity to synthesize a variety of NPs. So far, mostly cationic precursors have been used and only few studies have investigated the possibility of using amine groups to bind anionic precursors. Here, we use exponentially growing poly(L-lysine)/hyaluronan (PLL/HA) films as a nanoreservoir to bind and sequester aurochlorate (AuCl4−) anions thanks to the large number of free amine groups. The polypeptide-polysaccharide reactive template enabled the formation in a spatially-confined environment of gold NP at a very high yield. The synthesized gold NPs were homogenous and well-dispersed in the nanocomposite. Importantly, there was no particular effect of the film-ending layer (either PLL or HA). The largest particles of ~ 9 nm and the largest amount of gold were obtained at acidic pH of 3. When the pH was increased, smaller and more numerous NPs were synthesized but the total amount of gold was lower. Based on UV-visible spectrometry, FTIR and TEM data, we finally propose a scheme for the mechanism of gold NPs formation, in which several groups of PLL and HA contribute to the binding of gold ions, the nucleation and growth of NPs, and their stabilization in the “bulk” of the film. PMID:22981588

Poly(l-lysine)-graft-folic acid-coupled poly(2-methyl-2-oxazoline) (PLL-g-PMOXA-c-FA): a bioactive copolymer for specific targeting to folate receptor-positive cancer cells.

PubMed

Chen, Yin; Cao, Wenbin; Zhou, Junli; Pidhatika, Bidhari; Xiong, Bin; Huang, Lu; Tian, Qian; Shu, Yiwei; Wen, Weijia; Hsing, I-Ming; Wu, Hongkai

2015-02-04

In this study, we present the preparation, characterization and application of a novel bioactive copolymer poly(l-lysine)-graft-folic acid-coupled poly(2-methyl-2-oxazoline) (PLL-g-PMOXA-c-FA), which has a specific interaction with folate receptor (FR)-positive cancer cells. Glass surface immobilized with PLL-g-PMOXA-c-FA was demonstrated to be adhesive to FR-positive cancer cells (HeLa, JEG-3) while nonadhesive to FR-negative ones (MCF-7, HepG2) in 3 h. The specific interaction between conjugated FA on the substrate and FRs on the cells could hardly be inhibited unless a high concentration (5 mM) of free FA was used due to the multivalent nature of it. The FA functionality ratio of the copolymer on the substrate had a significant influence on the adhesion of HeLa cells, and our experiments revealed that the affinity of the substrate to the cells declined dramatically with the decrease of functionality ratio. This was believed to be caused by the polydispersity of PMOXA tethers, as supported by GPC and ToF-SIMS data. As a proof of concept in the application of our material, we demonstrated successful recovery of HeLa cells from mixture with MCF-7 (1:100) on the copolymer-coated glass, and our results showed that both high sensitivity (95.6 ± 13.3%) and specificity (24.3 ± 8.6%) were achieved.

Dependence of cancer cell adhesion kinetics on integrin ligand surface density measured by a high-throughput label-free resonant waveguide grating biosensor.

PubMed

Orgovan, Norbert; Peter, Beatrix; Bősze, Szilvia; Ramsden, Jeremy J; Szabó, Bálint; Horvath, Robert

2014-02-07

A novel high-throughput label-free resonant waveguide grating (RWG) imager biosensor, the Epic® BenchTop (BT), was utilized to determine the dependence of cell spreading kinetics on the average surface density (v(RGD)) of integrin ligand RGD-motifs. v(RGD) was tuned over four orders of magnitude by co-adsorbing the biologically inactive PLL-g-PEG and the RGD-functionalized PLL-g-PEG-RGD synthetic copolymers from their mixed solutions onto the sensor surface. Using highly adherent human cervical tumor (HeLa) cells as a model system, cell adhesion kinetic data of unprecedented quality were obtained. Spreading kinetics were fitted with the logistic equation to obtain the spreading rate constant (r) and the maximum biosensor response (Δλmax), which is assumed to be directly proportional to the maximum spread contact area (Amax). r was found to be independent of the surface density of integrin ligands. In contrast, Δλmax increased with increasing RGD surface density until saturation at high densities. Interpreting the latter behavior with a simple kinetic mass action model, a 2D dissociation constant of 1753 ± 243 μm(-2) (corresponding to a 3D dissociation constant of ~30 μM) was obtained for the binding between RGD-specific integrins embedded in the cell membrane and PLL-g-PEG-RGD. All of these results were obtained completely noninvasively without using any labels.

Sequential chemoimmunotherapy of fludarabine, mitoxantrone, and cyclophosphamide induction followed by alemtuzumab consolidation is effective in T-cell prolymphocytic leukemia.

PubMed

Hopfinger, Georg; Busch, Raymonde; Pflug, Natali; Weit, Nicole; Westermann, Anne; Fink, Anna-Maria; Cramer, Paula; Reinart, Nina; Winkler, Dirk; Fingerle-Rowson, Günter; Stilgenbauer, Stephan; Döhner, Hartmut; Kandler, Gabriele; Eichhorst, Barbara; Hallek, Michael; Herling, Marco

2013-06-15

Scarce systematic trial data have prevented uniform therapeutic guidelines for T-cell prolymphocytic leukemia (T-PLL). A central need in this historically refractory tumor is the controlled evaluation of multiagent chemotherapy and its combination with the currently most active single agent, alemtuzumab. This prospective multicenter phase 2 trial assessed response, survival, and toxicity of a novel regimen in previously treated (n = 9) and treatment-naive (n = 16) patients with T-PLL. Induction by fludarabine, mitoxantrone, and cyclophosphamide (FMC), for up to 4 cycles, was followed by alemtuzumab (A) consolidation, up to 12 weeks. Of the 25 patients treated with FMC, 21 subsequently received alemtuzumab. Overall response rate to FMC was 68%, comprising 6 complete remissions (all bone-marrow confirmed) and 11 partial remissions. Alemtuzumab consolidation increased the intent-to-treat overall response rate to 92% (12 complete remissions; 11 partial remissions). Median overall survival after FMC-A was 17.1 months and median progression-free survival was 11.9 months. Progression-free survival tended to be shorter for patients with high-level T-cell leukemia 1 oncoprotein expression. Hematologic toxicities were the most frequent grade 3/4 side effects under FMC-A. Exclusively in the 21 alemtuzumab-consolidated patients, 13 cytomegalovirus reactivations were observed; 9 of these 13 represented a clinically relevant infection. FMC-A is a safe and efficient protocol in T-PLL, which compares favorably to published data. Copyright © 2013 American Cancer Society.

Alginate Encapsulation of Pluripotent Stem Cells Using a Co-axial Nozzle

PubMed Central

Horiguchi, Ikki; Sakai, Yasuyuki

2015-01-01

Pluripotent stem cells (PS cells) are the focus of intense research due to their role in regenerative medicine and drug screening. However, the development of a mass culture system would be required for using PS cells in these applications. Suspension culture is one promising culture method for the mass production of PS cells, although some issues such as controlling aggregation and limiting shear stress from the culture medium are still unsolved. In order to solve these problems, we developed a method of calcium alginate (Alg-Ca) encapsulation using a co-axial nozzle. This method can control the size of the capsules easily by co-flowing N2 gas. The controllable capsule diameter must be larger than 500 µm because too high a flow rate of N2 gas causes the breakdown of droplets and thus heterogeneous-sized capsules. Moreover, a low concentration of Alg-Na and CaCl2 causes non-spherical capsules. Although an Alg-Ca capsule without a coating of Alg-PLL easily dissolves enabling the collection of cells, they can also potentially leak out from capsules lacking an Alg-PLL coating. Indeed, an alginate-PLL coating can prevent cellular leakage but is also hard to break. This technology can be used to research the stem cell niche as well as the mass production of PS cells because encapsulation can modify the micro-environment surrounding cells including the extracellular matrix and the concentration of secreted factors. PMID:26168084

Design and Calibration of the US Army Research Laboratory (ARL) Closed Loop Laboratory Radio Frequency (RF) Propagation Section

DTIC Science & Technology

2016-10-01

ARL-TR-7860 ● OCT 2016 US Army Research Laboratory Design and Calibration of the US Army Research Laboratory (ARL) Closed Loop ...ARL-TR-7860 ● OCT 2016 US Army Research Laboratory Design and Calibration of the US Army Research Laboratory (ARL) Closed Loop Laboratory...Design and Calibration of the US Army Research Laboratory (ARL) Closed Loop Laboratory Radio Frequency (RF) Propagation Section 5a. CONTRACT NUMBER

DOE Office of Scientific and Technical Information (OSTI.GOV)

N. Mittereder, A. Poerschke

This report presents a cold-climate project that examines an alternative approach to ground source heat pump (GSHP) ground loop design. The innovative ground loop design is an attempt to reduce the installed cost of the ground loop heat exchange portion of the system by containing the entire ground loop within the excavated location beneath the basement slab.

Design and implementation of co-operative control strategy for hybrid AC/DC microgrids

NASA Astrophysics Data System (ADS)

Mahmud, Rasel

This thesis is mainly divided in two major sections: 1) Modeling and control of AC microgrid, DC microgrid, Hybrid AC/DC microgrid using distributed co-operative control, and 2) Development of a four bus laboratory prototype of an AC microgrid system. At first, a distributed cooperative control (DCC) for a DC microgrid considering the state-of-charge (SoC) of the batteries in a typical plug-in-electric-vehicle (PEV) is developed. In DC microgrids, this methodology is developed to assist the load sharing amongst the distributed generation units (DGs), according to their ratings with improved voltage regulation. Subsequently, a DCC based control algorithm for AC microgrid is also investigated to improve the performance of AC microgrid in terms of power sharing among the DGs, voltage regulation and frequency deviation. The results validate the advantages of the proposed methodology as compared to traditional droop control of AC microgrid. The DCC-based control methodology for AC microgrid and DC microgrid are further expanded to develop a DCC-based power management algorithm for hybrid AC/DC microgrid. The developed algorithm for hybrid microgrid controls the power flow through the interfacing converter (IC) between the AC and DC microgrids. This will facilitate the power sharing between the DGs according to their power ratings. Moreover, it enables the fixed scheduled power delivery at different operating conditions, while maintaining good voltage regulation and improved frequency profile. The second section provides a detailed explanation and step-by-step design and development of an AC/DC microgrid testbed. Controllers for the three-phase inverters are designed and tested on different generation units along with their corresponding inductor-capacitor-inductor (LCL) filters to eliminate the switching frequency harmonics. Electric power distribution line models are developed to form the microgrid network topology. Voltage and current sensors are placed in the proper positions to achieve a full visibility over the microgrid. A running average filter (RAF) based enhanced phase-locked-loop (EPLL) is designed and implemented to extract frequency and phase angle information. A PLL-based synchronizing scheme is also developed to synchronize the DGs to the microgrid. The developed laboratory prototype runs on dSpace platform for real time data acquisition, communication and controller implementation.

Clinical and optical intraocular performance of rotationally asymmetric multifocal IOL plate-haptic design versus C-loop haptic design.

PubMed

Alió, Jorge L; Plaza-Puche, Ana B; Javaloy, Jaime; Ayala, María José; Vega-Estrada, Alfredo

2013-04-01

To compare the visual and intraocular optical quality outcomes with different designs of the refractive rotationally asymmetric multifocal intraocular lens (MFIOL) (Lentis Mplus; Oculentis GmbH, Berlin, Germany) with or without capsular tension ring (CTR) implantation. One hundred thirty-five consecutive eyes of 78 patients with cataract (ages 36 to 82 years) were divided into three groups: 43 eyes implanted with the C-Loop haptic design without CTR (C-Loop haptic only group); 47 eyes implanted with the C-Loop haptic design with CTR (C-Loop haptic with CTR group); and 45 eyes implanted with the plate-haptic design (plate-haptic group). Visual acuity, contrast sensitivity, defocus curve, and ocular and intraocular optical quality were evaluated at 3 months postoperatively. Significant differences in the postoperative sphere were found (P = .01), with a more myopic postoperative refraction for the C-Loop haptic only group. No significant differences were detected in photopic and scotopic contrast sensitivity among groups (P ⩾ .05). Significantly better visual acuities were present in the C-Loop haptic with CTR group for the defocus levels of -2.0, -1.5, -1.0, and -0.50 D (P ⩽.03). Statistically significant differences among groups were found in total intraocular root mean square (RMS), high-order intraocular RMS, and intraocular coma-like RMS aberrations (P ⩽.04), with lower values from the plate-haptic group. The plate-haptic design and the C-Loop haptic design with CTR implantation both allow good visual rehabilitation. However, better refractive predictability and intraocular optical quality was obtained with the plate-haptic design without CTR implantation. The plate-haptic design seems to be a better design to support rotational asymmetric MFIOL optics. Copyright 2013, SLACK Incorporated.

Resonance Frequency Readout Circuit for a 900 MHz SAW Device

PubMed Central

Liu, Heng; Zhang, Chun; Weng, Zhaoyang; Guo, Yanshu; Wang, Zhihua

2017-01-01

A monolithic resonance frequency readout circuit with high resolution and short measurement time is presented for a 900 MHz RF surface acoustic wave (SAW) sensor. The readout circuit is composed of a fractional-N phase-locked loop (PLL) as the stimulus source to the SAW device and a phase-based resonance frequency detecting circuit using successive approximation (SAR). A new resonance frequency searching strategy has been proposed based on the fact that the SAW device phase-frequency response crosses zero monotonically around the resonance frequency. A dedicated instant phase difference detecting circuit is adopted to facilitate the fast SAR operation for resonance frequency searching. The readout circuit has been implemented in 180 nm CMOS technology with a core area of 3.24 mm2. In the experiment, it works with a 900 MHz SAW resonator with a quality factor of Q = 130. Experimental results show that the readout circuit consumes 7 mW power from 1.6 V supply. The frequency resolution is 733 Hz, and the relative accuracy is 0.82 ppm, and it takes 0.48 ms to complete one measurement. Compared to the previous results in the literature, this work has achieved the shortest measurement time with a trade-off between measurement accuracy and measurement time. PMID:28914799

Resonance Frequency Readout Circuit for a 900 MHz SAW Device.

PubMed

Liu, Heng; Zhang, Chun; Weng, Zhaoyang; Guo, Yanshu; Wang, Zhihua

2017-09-15

A monolithic resonance frequency readout circuit with high resolution and short measurement time is presented for a 900 MHz RF surface acoustic wave (SAW) sensor. The readout circuit is composed of a fractional-N phase-locked loop (PLL) as the stimulus source to the SAW device and a phase-based resonance frequency detecting circuit using successive approximation (SAR). A new resonance frequency searching strategy has been proposed based on the fact that the SAW device phase-frequency response crosses zero monotonically around the resonance frequency. A dedicated instant phase difference detecting circuit is adopted to facilitate the fast SAR operation for resonance frequency searching. The readout circuit has been implemented in 180 nm CMOS technology with a core area of 3.24 mm². In the experiment, it works with a 900 MHz SAW resonator with a quality factor of Q = 130. Experimental results show that the readout circuit consumes 7 mW power from 1.6 V supply. The frequency resolution is 733 Hz, and the relative accuracy is 0.82 ppm, and it takes 0.48 ms to complete one measurement. Compared to the previous results in the literature, this work has achieved the shortest measurement time with a trade-off between measurement accuracy and measurement time.

A PLL-based resampling technique for vibration analysis in variable-speed wind turbines with PMSG: A bearing fault case

NASA Astrophysics Data System (ADS)

Pezzani, Carlos M.; Bossio, José M.; Castellino, Ariel M.; Bossio, Guillermo R.; De Angelo, Cristian H.

2017-02-01

Condition monitoring in permanent magnet synchronous machines has gained interest due to the increasing use in applications such as electric traction and power generation. Particularly in wind power generation, non-invasive condition monitoring techniques are of great importance. Usually, in such applications the access to the generator is complex and costly, while unexpected breakdowns results in high repair costs. This paper presents a technique which allows using vibration analysis for bearing fault detection in permanent magnet synchronous generators used in wind turbines. Given that in wind power applications the generator rotational speed may vary during normal operation, it is necessary to use special sampling techniques to apply spectral analysis of mechanical vibrations. In this work, a resampling technique based on order tracking without measuring the rotor position is proposed. To synchronize sampling with rotor position, an estimation of the rotor position obtained from the angle of the voltage vector is proposed. This angle is obtained from a phase-locked loop synchronized with the generator voltages. The proposed strategy is validated by laboratory experimental results obtained from a permanent magnet synchronous generator. Results with single point defects in the outer race of a bearing under variable speed and load conditions are presented.

Digital frequency offset-locked He–Ne laser system with high beat frequency stability, narrow optical linewidth and optical fibre output

NASA Astrophysics Data System (ADS)

Sternkopf, Christian; Manske, Eberhard

2018-06-01

We report on the enhancement of a previously-presented heterodyne laser source on the basis of two phase-locked loop (PLL) frequency coupled internal-mirror He–Ne lasers. Our new system consists of two digitally controlled He–Ne lasers with slightly different wavelengths, and offers high-frequency stability and very narrow optical linewidth. The digitally controlled system has been realized by using a FPGA controller and transconductance amplifiers. The light of both lasers was coupled into separate fibres for heterodyne interferometer applications. To enhance the laser performance we observed the sensitivity of both laser tubes to electromagnetic noise from various laser power supplies and frequency control systems. Furthermore, we describe how the linewidth of a frequency-controlled He–Ne laser can be reduced during precise frequency stabilisation. The digitally controlled laser source reaches a standard beat frequency deviation of less than 20 Hz (with 1 s gate time) and a spectral full width at half maximum (FWHM) of the beat signal less than 3 kHz. The laser source has enough optical output power to serve a fibre-coupled multi axis heterodyne interferometer. The system can be adjusted to output beat frequencies in the range of 0.1 MHz–20 MHz.

Electrochemical quartz crystal microbalance study of polyelectrolyte film growth under anodic conditions

NASA Astrophysics Data System (ADS)

Nilsson, Sara; Björefors, Fredrik; Robinson, Nathaniel D.

2013-09-01

Coating hard materials such as Pt with soft polymers like poly-L-lysine is a well-established technique for increasing electrode biocompatibility. We have combined quartz crystal microgravimetry with dissipation with electrochemistry (EQCM-D) to study the deposition of PLL onto Pt electrodes under anodic potentials. Our results confirm the change in film growth over time previously reported by others. However, the dissipation data suggest that, after the short initial phase of the process, the rigidity of the film increases with time, rather than decreasing, as previously proposed. In addition to these results, we discuss how gas evolution from water electrolysis and Pt etching in electrolytes containing Cl- affect EQCM-D measurements, how to recognize these effects, and how to reduce them. Despite the challenges of using Pt as an anode in this system, we demonstrate that the various electrochemical processes can be understood and that PLL coatings can be successfully electrodeposited.

Doxorubicin Delivery Using pH and Redox Dual-Responsive Hollow Nanocapsules with a Cationic Electrostatic Barrier

PubMed Central

Teranishi, Ryoma; Matsuki, Ryota; Yuba, Eiji; Harada, Atsushi; Kono, Kenji

2016-01-01

For the delivery of doxorubicin (DOX), pH and redox dual responsive hollow nanocapsules were prepared through the stabilization of polymer vesicles, which spontaneously formed from polyamidoamine dendron-poly(l-lysine) (PAMAM dendron-PLL), by the introduction of disulfide (SS) bonds between PLLs. The SS-bonded nanocapsules exhibited a very slow release of DOX under an extracellular environment because the cationic PLL membrane acted as an electrostatic barrier against the protonated DOX molecules. However, increasing the glutathione concentration to the intracellular level facilitated the immediate release of DOX through the collapse of nanocapsules by the spontaneous cleavage of SS bonds. SS-bonded nanocapsules also escaped from the endosome by the buffering effect of PAMAM dendrons, and DOX delivery into the cytoplasm was achieved. Furthermore, DOX molecules delivered by SS-bonded nanocapsules exhibited an effective in vitro anticancer effect to HeLa cells. PMID:28042818

Quantum transport in graphene in presence of strain-induced pseudo-Landau levels

NASA Astrophysics Data System (ADS)

Settnes, Mikkel; Leconte, Nicolas; Barrios-Vargas, Jose E.; Jauho, Antti-Pekka; Roche, Stephan

2016-09-01

We report on mesoscopic transport fingerprints in disordered graphene caused by strain-field induced pseudomagnetic Landau levels (pLLs). Efficient numerical real space calculations of the Kubo formula are performed for an ordered network of nanobubbles in graphene, creating pseudomagnetic fields up to several hundreds of Tesla, values inaccessible by real magnetic fields. Strain-induced pLLs yield enhanced scattering effects across the energy spectrum resulting in lower mean free path and enhanced localization effects. In the vicinity of the zeroth order pLL, we demonstrate an anomalous transport regime, where the mean free paths increases with disorder. We attribute this puzzling behavior to the low-energy sub-lattice polarization induced by the zeroth order pLL, which is unique to pseudomagnetic fields preserving time-reversal symmetry. These results, combined with the experimental feasibility of reversible deformation fields, open the way to tailor a metal-insulator transition driven by pseudomagnetic fields.

Biodegradable protein-based rockets for drug transportation and light-triggered release.

PubMed

Wu, Zhiguang; Lin, Xiankun; Zou, Xian; Sun, Jianmin; He, Qiang

2015-01-14

We describe a biodegradable, self-propelled bovine serum albumin/poly-l-lysine (PLL/BSA) multilayer rocket as a smart vehicle for efficient anticancer drug encapsulation/delivery to cancer cells and near-infrared light controlled release. The rockets were constructed by a template-assisted layer-by-layer assembly of the PLL/BSA layers, followed by incorporation of a heat-sensitive gelatin hydrogel containing gold nanoparticles, doxorubicin, and catalase. These rockets can rapidly deliver the doxorubicin to the targeted cancer cell with a speed of up to 68 μm/s, through a combination of biocatalytic bubble propulsion and magnetic guidance. The photothermal effect of the gold nanoparticles under NIR irradiation enable the phase transition of the gelatin hydrogel for rapid release of the loaded doxorubicin and efficient killing of the surrounding cancer cells. Such biodegradable and multifunctional protein-based microrockets provide a convenient and efficient platform for the rapid delivery and controlled release of therapeutic drugs.

Emulsion-core and polyelectrolyte-shell nanocapsules: biocompatibility and neuroprotection against SH-SY5Y cells

NASA Astrophysics Data System (ADS)

Piotrowski, Marek; Szczepanowicz, Krzysztof; Jantas, Danuta; Leśkiewicz, Monika; Lasoń, Władysław; Warszyński, Piotr

2013-11-01

The emulsion-core and polyelectrolyte-coated nanocapsules, designed as water-insoluble neuroprotective drug delivery system, were synthesized using layer-by-layer saturation method. The isopropyl myristate was used as oil phase and docusate sodium salt as emulsifier. For the polyelectrolyte shell preparation, synthetic polyelectrolytes, cationic (PDADMAC, PAH, and PLL) and anionic (PGA) were used. The particle size and zeta potential of nanocapsules were characterized by the dynamic light scattering. The average size of synthesized nanocapsules ranged from 80 to 100 nm. Zeta potential values ranged from less than approximately -30 mV for the polyanion layers to greater than approximately +30 mV for the polycation layers. Biocompatibilities of the synthesized nanocarriers were evaluated against SH-SY5Y human neuroblastoma cells using various biochemical assays. The results obtained show that synthesized nanocapsules coated with PLL and PGA were nontoxic to SH-SY5Y cells, and they were used as nanocarriers for model neuroprotective drug (a calpain inhibitor MDL 28170). The neuroprotective action of the encapsulated MDL 28170 against hydrogen peroxide-induced oxidative stress cytotoxicity was evaluated in the same cell line. The results showed that nanoencapsulated form of MDL 28170 were biocompatible and protected SH-SY5Y cells against the H2O2 (0.5 mM/24 h)-induced damage in 20-40 times lower concentrations than those of the same drug added directly to the culture medium. These data suggest that the nanoscale carriers of neuroprotective drugs might serve as novel promising therapeutic agents for oxidative stress-related neurodegenerative processes.

Phase-locked loops. [in analog and digital circuits communication system

NASA Technical Reports Server (NTRS)

Gupta, S. C.

1975-01-01

An attempt to systematically outline the work done in the area of phase-locked loops which are now used in modern communication system design is presented. The analog phase-locked loops are well documented in several books but discrete, analog-digital, and digital phase-locked loop work is scattered. Apart from discussing the various analysis, design, and application aspects of phase-locked loops, a number of references are given in the bibliography.

Labeling Efficacy of Superparamagnetic Iron Oxide Nanoparticles to Human Neural Stem Cells: Comparison of Ferumoxides, Monocrystalline Iron Oxide, Cross-linked Iron Oxide (CLIO)-NH2 and tat-CLIO

PubMed Central

Song, Miyeoun; Kim, Yunhee; Lim, Dongyeol; Song, In-Chan; Yoon, Byung-Woo

2007-01-01

Objective We wanted to compare the human neural stem cell (hNSC) labeling efficacy of different superparamagnetic iron oxide nanoparticles (SPIONs), namely, ferumoxides, monocrystalline iron oxide (MION), cross-linked iron oxide (CLIO)-NH2 and tat-CLIO. Materials and Methods The hNSCs (5 × 105 HB1F3 cells/ml) were incubated for 24 hr in cell culture media that contained 25 µg/ml of ferumoxides, MION or CLIO-NH2, and with or without poly-L-lysine (PLL) and tat-CLIO. The cellular iron uptake was analyzed qualitatively with using a light microscope and this was quantified via atomic absorption spectrophotometry. The visibility of the labeled cells was assessed with MR imaging. Results The incorporation of SPIONs into the hNSCs did not affect the cellular proliferations and viabilities. The hNSCs labeled with tat-CLIO showed the longest retention, up to 72 hr, and they contained 2.15 ± 0.3 pg iron/cell, which are 59 fold, 430 fold and six fold more incorporated iron than that of the hNSCs labeled with ferumoxides, MION or CLIO-NH2, respectively. However, when PLL was added, the incorporation of ferumoxides, MION or CLIO-NH2 into the hNSCs was comparable to that of tat-CLIO. Conclusion For MR imaging, hNSCs can be efficiently labeled with tat-CLIO alone or with a combination of ferumoxides, MION, CLIO-NH2 and the transfection agent PLL. PMID:17923778

Adsorption of transgenic insecticidal Cry1Ab protein to SiO2. 2. Patch-controlled electrostatic attraction.

PubMed

Madliger, Michael; Sander, Michael; Schwarzenbach, René P

2010-12-01

Adsorption governs the fate of Cry proteins from genetically modified Bt crops in soils. The effect of ionic strength (I) on the adsorption of Cry1Ab (isoelectric point IEP(Cry1Ab) ≈ 6) to negatively charged quartz (SiO(2)) and positively charged poly-L-lysine (PLL) was investigated at pH 5 to 8, using quartz crystal microbalance with dissipation monitoring and optical waveguide lightmode spectroscopy. Cry1Ab adsorbed via positively and negatively charged surface patches to SiO(2) and PLL, respectively. This patch controlled electrostatic attraction (PCEA) explains the observed increase in Cry1Ab adsorption to sorbents that carried the same net charge as the protein (SiO(2) at pH > IEP(Cry1Ab) and PLL at pH < IEP(Cry1Ab)) with decreasing I. In contrast, the adsorption of two reference proteins, BSA and HEWL, with different adsorption mechanism, were little affected by similar changes of I. Consistent with PCEA, Cry1Ab desorption from SiO(2) at pH > IEP(Cry1Ab) increased with increasing I and pH. Weak Cry1Ab-SiO(2) PCEA above pH 7 resulted in reversible, concentration dependent adsorption. Solution depletion experiments showed that PCEA also governed Cry1Ab adsorption to SiO(2) particles at environmentally relevant concentrations (a few ng mL(-1)). These results imply that models describing Cry1Ab adsorption to charged surfaces in soils need to account for the nonuniform surface charge distribution of the protein.

Chitosan/γ-poly(glutamic acid) scaffolds with surface-modified albumin, elastin and poly-l-lysine for cartilage tissue engineering.

PubMed

Kuo, Yung-Chih; Ku, Hao-Fu; Rajesh, Rajendiran

2017-09-01

Cartilage has limited ability to self-repair due to the absence of blood vessels and nerves. The application of biomaterial scaffolds using biomimetic extracellular matrix (ECM)-related polymers has become an effective approach to production of engineered cartilage. Chitosan/γ-poly(glutamic acid) (γ-PGA) scaffolds with different mass ratios were prepared using genipin as a cross-linker and a freeze-drying method, and their surfaces were modified with elastin, human serum albumin (HSA) and poly-l-lysine (PLL). The scaffolds were formed through a complex between NH 3 + of chitosan and COO - of γ-PGA, confirmed by Fourier transform infrared spectroscopy, and exhibited an interconnected porous morphology in field emission scanning electron microscopy analysis. The prepared chitosan/γ-PGA scaffolds, at a 3:1 ratio, obtained the required porosity (90%), pore size (≥100μm), mechanical strength (compressive strength>4MPa, Young's modulus>4MPa) and biodegradation (30-60%) for articular cartilage tissue engineering applications. Surface modification of the scaffolds showed positive indications with improved activity toward cell proliferation (deoxyribonucleic acid), cell adhesion and ECM (glycoaminoglycans and type II collagen) secretion of bovine knee chondrocytes compared with unmodified scaffolds. In caspase-3 detection, elastin had a higher inhibitory effect on chondrocyte apoptosis in vitro, followed by HSA, and then PLL. We concluded that utilizing chitosan/γ-PGA scaffolds with surface active biomolecules, including elastin, HSA and PLL, can effectively promote the growth of chondrocytes, secrete ECM and improve the regenerative ability of cartilaginous tissues. Copyright © 2017 Elsevier B.V. All rights reserved.

Substrate-based near-infrared imaging sensors enable fluorescence lifetime contrast via built-in dynamic fluorescence quenching elements.

PubMed

Kumar, Anand T N; Rice, William L; López, Jessica C; Gupta, Suresh; Goergen, Craig J; Bogdanov, Alexei A

2016-04-22

Enzymatic activity sensing in fluorescence lifetime (FLT) mode with "self-quenched" macromolecular near-infrared (NIR) sensors is a highly promising strategy for in vivo imaging of proteolysis. However, the mechanisms of FLT changes in such substrate-based NIR sensors have not yet been studied. We synthesized two types of sensors by linking the near-infrared fluorophore IRDye 800CW to macromolecular graft copolymers of methoxy polyethylene glycol and polylysine (MPEG-gPLL) with varying degrees of MPEGylation and studied their fragmentation induced by trypsin, elastase, plasmin and cathepsins (B,S,L,K). We determined that the efficiency of such NIR sensors in FLT mode depends on sensor composition. While MPEG-gPLL with a high degree of MPEGylation showed rapid (τ 1/2 =0.1-0.2 min) FLT increase (Δτ=0.25 ns) upon model proteinase-mediated hydrolysis in vivo , lower MPEGylation density resulted in no such FLT increase. Temperature-dependence of fluorescence de-quenching of NIR sensors pointed to a mixed dynamic/static-quenching mode of MPEG-gPLL-linked fluorophores. We further demonstrated that although the bulk of sensor-linked fluorophores were de-quenched due to the elimination of static quenching, proteolysis-mediated deletion of a fraction of short (8-10kD) negatively charged fragments of highly MPEGylated NIR sensor is the most likely event leading to a rapid FLT increase phenomenon in quenched NIR sensors. Therefore, the optimization of "built-in" dynamic quenching elements of macromolecular NIR sensors is a potential avenue for improving their response in FLT mode.

Polymer nanoassemblies with hydrophobic pendant groups in the core induce false positive siRNA transfection in luciferase reporter assays.

PubMed

Rheiner, Steven; Reichel, Derek; Rychahou, Piotr; Izumi, Tadahide; Yang, Hsin-Sheng; Bae, Younsoo

2017-08-07

Poly(ethylene glycol)-conjugated polyethylenimine (PEG-PEI) is a widely studied cationic polymer used to develop non-viral vectors for siRNA therapy of genetic disorders including cancer. Cell lines stably expressing luciferase reporter protein typically evaluate the transfection efficacy of siRNA/PEG-PEI complexes, however recent findings revealed that PEG-PEI can reduce luciferase expression independent of siRNA. This study elucidates a cause of the false positive effect in luciferase assays by using polymer nanoassemblies (PNAs) made from PEG, PEI, poly-(l-lysine) (PLL), palmitate (PAL), and deoxycholate (DOC): PEG-PEI (2P), PEG-PEI-PAL (3P), PEG-PLL (2P'), PEG-PLL-PAL (3P'), and PEG-PEI-DOC (2PD). In vitro transfection and western blot assays of luciferase using a colorectal cancer cell line expressing luciferase (HT29/LUC) concluded that 2P and 2P' caused no luciferase expression reduction while hydrophobically modified PNAs induced a 35-50% reduction (3P'<2PD<3P). Although cell viability remained stagnant, 3P triggered cellular stress responses including increased membrane porosity and decreased ATP and cellular protein concentrations. Raman spectroscopy suggested that hydrophobic groups influence PNA conformation changes, which may have caused over-ubiquitination and degradation of luciferase in the cells. These results indicate that hydrophobically modified PEG-PEI induces cellular distress causing over-ubiquitination of the luciferase protein, producing false positive siRNA transfection in the luciferase assay. Copyright © 2017 Elsevier B.V. All rights reserved.

All-digital phase-lock loops for noise-free signals

NASA Technical Reports Server (NTRS)

Anderson, T. O.

1973-01-01

Bit-synchronizers utilize all-digital phase-lock loops that are referenced to a high frequency digital clock. Phase-lock loop of first design acquires frequency within nominal range and tracks phase; second design is modified for random binary data by addition of simple transition detector; and third design acquires frequency over wide dynamic range.

Synthesis of antireflective silica coatings through the synergy of polypeptide layer-by-layer assemblies and biomineralization

NASA Astrophysics Data System (ADS)

Lee, Yung-Lun; Lin, Ting-Xuan; Hsu, Feng-Ming; Jan, Jeng-Shiung

2016-01-01

We report a versatile approach to synthesize silica coatings with antireflective (AR) characteristics through the combination of a layer-by-layer (LbL) assembly technique and biomineralization. LbL assembled decanoyl-modified poly(l-lysine)/poly(l-glutamic acid) (PLL-g-Dec/PLGA) multilayer films were used as templates for silica mineralization, followed by calcination. The specific deposition of silica onto the LbL polypeptide assemblies through amine-catalyzed polycondensation resulted in silica coatings that exhibited the transcription of the nano-/microstructured polypeptide films and their film thickness and porosity can be tuned by varying the number of bilayers, degree of substitution, and PLL molecular weight. AR silica coatings exhibiting more than 6% increase in transmittance in the near UV/visible spectral range can be obtained at an optimized refractive index, thickness, and surface roughness. The abrasion test showed that the silica coatings exhibited sufficient structural durability due to continuous silica nanostructures and low surface roughness. This study demonstrated that nanostructured thin films can be synthesized for AR coatings using the synergy between the LbL assembly technique and biomineralization.We report a versatile approach to synthesize silica coatings with antireflective (AR) characteristics through the combination of a layer-by-layer (LbL) assembly technique and biomineralization. LbL assembled decanoyl-modified poly(l-lysine)/poly(l-glutamic acid) (PLL-g-Dec/PLGA) multilayer films were used as templates for silica mineralization, followed by calcination. The specific deposition of silica onto the LbL polypeptide assemblies through amine-catalyzed polycondensation resulted in silica coatings that exhibited the transcription of the nano-/microstructured polypeptide films and their film thickness and porosity can be tuned by varying the number of bilayers, degree of substitution, and PLL molecular weight. AR silica coatings exhibiting more than 6% increase in transmittance in the near UV/visible spectral range can be obtained at an optimized refractive index, thickness, and surface roughness. The abrasion test showed that the silica coatings exhibited sufficient structural durability due to continuous silica nanostructures and low surface roughness. This study demonstrated that nanostructured thin films can be synthesized for AR coatings using the synergy between the LbL assembly technique and biomineralization. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06948c

Analysis of first and second order binary quantized digital phase-locked loops for ideal and white Gaussian noise inputs

NASA Technical Reports Server (NTRS)

Blasche, P. R.

1980-01-01

Specific configurations of first and second order all digital phase locked loops are analyzed for both ideal and additive white gaussian noise inputs. In addition, a design for a hardware digital phase locked loop capable of either first or second order operation is presented along with appropriate experimental data obtained from testing of the hardware loop. All parameters chosen for the analysis and the design of the digital phase locked loop are consistent with an application to an Omega navigation receiver although neither the analysis nor the design are limited to this application.

A Robust Inner and Outer Loop Control Method for Trajectory Tracking of a Quadrotor

PubMed Central

Xia, Dunzhu; Cheng, Limei; Yao, Yanhong

2017-01-01

In order to achieve the complicated trajectory tracking of quadrotor, a geometric inner and outer loop control scheme is presented. The outer loop generates the desired rotation matrix for the inner loop. To improve the response speed and robustness, a geometric SMC controller is designed for the inner loop. The outer loop is also designed via sliding mode control (SMC). By Lyapunov theory and cascade theory, the closed-loop system stability is guaranteed. Next, the tracking performance is validated by tracking three representative trajectories. Then, the robustness of the proposed control method is illustrated by trajectory tracking in presence of model uncertainty and disturbances. Subsequently, experiments are carried out to verify the method. In the experiment, ultra wideband (UWB) is used for indoor positioning. Extended Kalman Filter (EKF) is used for fusing inertial measurement unit (IMU) and UWB measurements. The experimental results show the feasibility of the designed controller in practice. The comparative experiments with PD and PD loop demonstrate the robustness of the proposed control method. PMID:28925984

IN-PILE CORROSION TEST LOOPS FOR AQUEOUS HOMOGENEOUS REACTOR SOLUTIONS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Savage, H.C.; Jenks, G.H.; Bohlmann, E.G.

1960-12-21

An in-pile corrosion test loop is described which is used to study the effect of reactor radiation on the corrosion of materials of construction and the chemical stability of fuel solutions of interest to the Aqueous Homogeneous Reactor Program at ORNL. Aqueous solutions of uranyl sulfate are circulated in the loop by means of a 5-gpm canned-rotor pump, and the pump loop is designed for operation at temperatures to 300 ts C and pressures to 2000 psia while exposed to reactor radiation in beam-hole facilities of the LITR and ORR. Operation of the first loop in-pile was begun in Octobermore » 1954, and since that time 17 other in-pile loop experiments were completed. Design criteria of the pump loop and its associated auxiliary equipment and instrumentation are described. In-pile operating procedures, safety features, and operating experience are presented. A cost summary of the design, fabrication, and installation of the loop and experimental facillties is also included. (auth)« less

Innovative design of closing loops producing an optimal force system applicable in the 0.022-in bracket slot system.

PubMed

Sumi, Mayumi; Koga, Yoshiyuki; Tominaga, Jun-Ya; Hamanaka, Ryo; Ozaki, Hiroya; Chiang, Pao-Chang; Yoshida, Noriaki

2016-12-01

Most closing loops designed for producing higher moment-to-force (M/F) ratios require complex wire bending and are likely to cause hygiene problems and discomfort because of their complicated configurations. We aimed to develop a simple loop design that can produce optimal force and M/F ratio. A loop design that can generate a high M/F ratio and the ideal force level was investigated by varying the portion and length of the cross-sectional reduction of a teardrop loop and the loop position. The forces and moments acting on closing loops were calculated using structural analysis based on the tangent stiffness method. An M/F ratio of 9.3 (high enough to achieve controlled movement of the anterior teeth) and an optimal force level of approximately 250 g of force can be generated by activation of a 10-mm-high teardrop loop whose cross-section of 0.019 × 0.025 or 0.021 × 0.025 in was reduced in thickness by 50% for a distance of 3 mm from the apex, located between a quarter and a third of the interbracket distance from the canine bracket. The simple loop design that we developed delivers an optimal force and an M/F ratio for the retraction of anterior teeth, and is applicable in a 0.022-in slot system. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Robust Adaptive Flight Control Design of Air-breathing Hypersonic Vehicles

DTIC Science & Technology

2016-12-07

dynamic inversion controller design for a non -minimum phase hypersonic vehicle is derived by Kuipers et al. [2008]. Moreover, integrated guidance and...stabilization time for inner loop variables is lesser than the intermediate loop variables because of the three-loop-control design methodology . The control...adaptive design . Control Engineering Practice, 2016. Michael A Bolender and David B Doman. A non -linear model for the longitudinal dynamics of a

Aviation Human-in-the-Loop Simulation Studies: Experimental Planning, Design, and Data Management

DTIC Science & Technology

2014-01-01

Aviation Human-in-the-Loop Simulation Studies: Experimental Planning, Design , and Data Management Kevin W. Williams1 Bonny Christopher2 Gena...Simulation Studies: Experimental Planning, Design , and Data Management January 2014 6. Performing Organization Code 7. Author(s) 8. Performing...describe the process by which we designed our human-in-the-loop (HITL) simulation study and the methodology used to collect and analyze the results

Phase-lock-loop application for fiber optic receiver

NASA Astrophysics Data System (ADS)

Ruggles, Stephen L.; Wills, Robert W.

1991-02-01

Phase-locked loop circuits are frequently employed in communication systems. In recent years, digital phase-locked loop circuits were utilized in optical communications systems. In an optical transceiver system, the digital phase-locked loop circuit is connected to the output of the receiver to extract a clock signal from the received coded data (NRZ, Bi-Phase, or Manchester). The clock signal is then used to reconstruct or recover the original data from the coded data. A theoretical approach to the design of a digital phase-locked loop circuit operation at 1 and 50 MHz is described. Hardware implementation of a breadboard design to function at 1 MHz and a printed-circuit board designed to function at 50 MHz were assembled using emitter coupled logic (ECL) to verify experimentally the theoretical design.

Phase-lock-loop application for fiber optic receiver

NASA Technical Reports Server (NTRS)

Ruggles, Stephen L.; Wills, Robert W.

1991-01-01

Phase-locked loop circuits are frequently employed in communication systems. In recent years, digital phase-locked loop circuits were utilized in optical communications systems. In an optical transceiver system, the digital phase-locked loop circuit is connected to the output of the receiver to extract a clock signal from the received coded data (NRZ, Bi-Phase, or Manchester). The clock signal is then used to reconstruct or recover the original data from the coded data. A theoretical approach to the design of a digital phase-locked loop circuit operation at 1 and 50 MHz is described. Hardware implementation of a breadboard design to function at 1 MHz and a printed-circuit board designed to function at 50 MHz were assembled using emitter coupled logic (ECL) to verify experimentally the theoretical design.

A novel double loop control model design for chemical unstable processes.

PubMed

Cong, Er-Ding; Hu, Ming-Hui; Tu, Shan-Tung; Xuan, Fu-Zhen; Shao, Hui-He

2014-03-01

In this manuscript, based on Smith predictor control scheme for unstable process in industry, an improved double loop control model is proposed for chemical unstable processes. Inner loop is to stabilize integrating the unstable process and transform the original process to first-order plus pure dead-time dynamic stable process. Outer loop is to enhance the performance of set point response. Disturbance controller is designed to enhance the performance of disturbance response. The improved control system is simple with exact physical meaning. The characteristic equation is easy to realize stabilization. Three controllers are separately design in the improved scheme. It is easy to design each controller and good control performance for the respective closed-loop transfer function separately. The robust stability of the proposed control scheme is analyzed. Finally, case studies illustrate that the improved method can give better system performance than existing design methods. © 2013 ISA Published by ISA All rights reserved.

Building America Case Study: Simplified Air Distribution, Desuperheaters, and Sub-Slab Geothermal Heat Exchangers, Pittsburgh, Pennsylvania

DOE Office of Scientific and Technical Information (OSTI.GOV)

This report presents a cold-climate project that examines an alternative approach to ground source heat pump (GSHP) ground loop design. The innovative ground loop design is an attempt to reduce the installed cost of the ground loop heat exchange portion of the system by containing the entire ground loop within the excavated location beneath the basement slab.

Controlled-Root Approach To Digital Phase-Locked Loops

NASA Technical Reports Server (NTRS)

Stephens, Scott A.; Thomas, J. Brooks

1995-01-01

Performance tailored more flexibly and directly to satisfy design requirements. Controlled-root approach improved method for analysis and design of digital phase-locked loops (DPLLs). Developed rigorously from first principles for fully digital loops, making DPLL theory and design simpler and more straightforward (particularly for third- or fourth-order DPLL) and controlling performance more accurately in case of high gain.

Investigation, development and application of optimal output feedback theory. Volume 2: Development of an optimal, limited state feedback outer-loop digital flight control system for 3-D terminal area operation

NASA Technical Reports Server (NTRS)

Broussard, J. R.; Halyo, N.

1984-01-01

This report contains the development of a digital outer-loop three dimensional radio navigation (3-D RNAV) flight control system for a small commercial jet transport. The outer-loop control system is designed using optimal stochastic limited state feedback techniques. Options investigated using the optimal limited state feedback approach include integrated versus hierarchical control loop designs, 20 samples per second versus 5 samples per second outer-loop operation and alternative Type 1 integration command errors. Command generator tracking techniques used in the digital control design enable the jet transport to automatically track arbitrary curved flight paths generated by waypoints. The performance of the design is demonstrated using detailed nonlinear aircraft simulations in the terminal area, frequency domain multi-input sigma plots, frequency domain single-input Bode plots and closed-loop poles. The response of the system to a severe wind shear during a landing approach is also presented.

Irradiation Testing Vehicles for Fast Reactors from Open Test Assemblies to Closed Loops

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sienicki, James J.; Grandy, Christopher

A review of irradiation testing vehicle approaches and designs that have been incorporated into past Sodium-Cooled Fast Reactors (SFRs) or envisioned for incorporation has been carried out. The objective is to understand the essential features of the approaches and designs so that they can inform test vehicle designs for a future U.S. Fast Test Reactor. Fast test reactor designs examined include EBR-II, FFTF, JOYO, BOR-60, PHÉNIX, JHR, and MBIR. Previous designers exhibited great ingenuity in overcoming design and operational challenges especially when the original reactor plant’s mission changed to an irradiation testing mission as in the EBRII reactor plant. Themore » various irradiation testing vehicles can be categorized as: Uninstrumented open assemblies that fit into core locations; Instrumented open test assemblies that fit into special core locations; Self-contained closed loops; and External closed loops. A special emphasis is devoted to closed loops as they are regarded as a very desirable feature of a future U.S. Fast Test Reactor. Closed loops are an important technology for irradiation of fuels and materials in separate controlled environments. The impact of closed loops on the design of fast reactors is also discussed in this report.« less

Biomolecular strategies for cell surface engineering

NASA Astrophysics Data System (ADS)

Wilson, John Tanner

Islet transplantation has emerged as a promising cell-based therapy for the treatment of diabetes, but its clinical efficacy remains limited by deleterious host responses that underlie islet destruction. In this dissertation, we describe the assembly of ultrathin conformal coatings that confer molecular-level control over the composition and biophysicochemical properties of the islet surface with implications for improving islet engraftment. Significantly, this work provides novel biomolecular strategies for cell surface engineering with broad biomedical and biotechnological applications in cell-based therapeutics and beyond. Encapsulation of cells and tissue offers a rational approach for attenuating deleterious host responses towards transplanted cells, but a need exists to develop cell encapsulation strategies that minimize transplant volume. Towards this end, we endeavored to generate nanothin films of diverse architecture with tunable properties on the extracellular surface of individual pancreatic islets through a process of layer-by-layer (LbL) self assembly. We first describe the formation of poly(ethylene glycol) (PEG)-rich conformal coatings on islets via LbL self assembly of poly(L-lysine)-g-PEG(biotin) and streptavidin. Multilayer thin films conformed to the geometrically and chemically heterogeneous islet surface, and could be assembled without loss of islet viability or function. Significantly, coated islets performed comparably to untreated controls in a murine model of allogenic intraportal islet transplantation, and, to our knowledge, this is the first study to report in vivo survival and function of nanoencapsulated cells or cell aggregates. Based on these findings, we next postulated that structurally similar PLL-g-PEG copolymers comprised of shorter PEG grafts might be used to initiate and propagate the assembly of polyelectrolyte multilayer (PEM) films on pancreatic islets, while simultaneously preserving islet viability. Through control of PLL backbone molecular weight, PEG chain length, and grafting ratio, PLL-g-PEG copolymers were rendered cytocompatible and used to initiate and propagate the growth of cell surface-supported PEM films. Planar characterization of this novel class of PEM films indicated that film thickness and composition may be tailored through appropriate control of layer number and copolymer properties. Furthermore, these investigations have helped establish a conceptual framework for the rational design of cell surface-supported thin films, with the objective of translating the diverse biomedical and biotechnological applications of PEM films to cellular interfaces. Important to the development of effective conformal islet coatings is an inherent strategy through which to incorporate bioactive molecules for directing desired biochemical or cellular responses. Towards this end, PLL-g-PEG copolymers functionalized with biotin, azide, and hydrazide moieties were synthesized and used, either alone or in combination, to capture streptavidin-, triphenylphosphine-, and aldehyde-labeled probes, respectively, on the islet surface. Additionally, PEM films assembled using alginate chemically modified to contain aldehyde groups could be used to introduce hydrazide-functionalized molecules to the islet surface. Hence, modified film constituents may be used as modular elements for controlling the chemical composition cell and tissue surfaces. Finally, we report a strategy for tethering thrombomodulin (TM) to the islet surface. Through site-specific, C-terminal biotinylation of TM and optimization of cell surface biotinylation, TM could be integrated with the islet surface. Re-engineering of islet surfaces with TM resulted in an increased catalytic capacity of islets to generate the powerful anti-inflammatory agent, activated protein C (APC), thereby providing a facile strategy for increasing the local concentration of APC at the site of transplantation.

Feedback control laws for highly maneuverable aircraft

NASA Technical Reports Server (NTRS)

Garrard, William L.; Balas, Gary J.

1994-01-01

During the first half of the year, the investigators concentrated their efforts on completing the design of control laws for the longitudinal axis of the HARV. During the second half of the year they concentrated on the synthesis of control laws for the lateral-directional axes. The longitudinal control law design efforts can be briefly summarized as follows. Longitudinal control laws were developed for the HARV using mu synthesis design techniques coupled with dynamic inversion. An inner loop dynamic inversion controller was used to simplify the system dynamics by eliminating the aerodynamic nonlinearities and inertial cross coupling. Models of the errors resulting from uncertainties in the principal longitudinal aerodynamic terms were developed and included in the model of the HARV with the inner loop dynamic inversion controller. This resulted in an inner loop transfer function model which was an integrator with the modeling errors characterized as uncertainties in gain and phase. Outer loop controllers were then designed using mu synthesis to provide robustness to these modeling errors and give desired response to pilot inputs. Both pitch rate and angle of attack command following systems were designed. The following tasks have been accomplished for the lateral-directional controllers: inner and outer loop dynamic inversion controllers have been designed; an error model based on a linearized perturbation model of the inner loop system was derived; controllers for the inner loop system have been designed, using classical techniques, that control roll rate and Dutch roll response; the inner loop dynamic inversion and classical controllers have been implemented on the six degree of freedom simulation; and lateral-directional control allocation scheme has been developed based on minimizing required control effort.

Molecular Level Investigations of Interfacial Friction of Polymer Brush Surfaces

NASA Astrophysics Data System (ADS)

Perry, Scott

2005-03-01

The development of synthetic polymer lubricants to mimic joint lubrication within the human body will be presented. Unlike most industrial applications involving oils and greases, lubrication of these joints is accomplished in an aqueous environment. Fundamentally, water is a poor lubricant in most settings due to the weak pressure dependence of its viscosity, yet the contacting surfaces of skeletal joints function with low friction throughout a lifetime. Motivated by the molecular structure of materials making up joint surfaces, interfacial friction between polymer brush surfaces under aqueous environments has been probed with an array of molecularly sensitive surface analytical techniques including atomic force microscopy. The brush surfaces, comprised of poly(L-lysine)-g-poly(ethylene glycol) (PLL-g-PEG), have been generated through the spontaneous adsorption of polymer from solution onto oxide substrates and sodium borosilicate surfaces (AFM tip). The character of the polymer films has been investigated in-situ with the quartz crystal microbalance (QCM) and atomic force microscope (AFM) and ex-situ with ellipsometry and X-ray photoelectron spectroscopy (XPS). The interfacial friction measurements have been carried out on polymer-coated substrates with bare or polymer-coated, microsphere-attached tips in over a range of solution conditions. It was found that the adsorption of polymer on oxides strikingly reduced the interfacial friction, resulting in ultra-low friction under certain conditions. By using a series of PLL-g-PEG polymers differing from each other in PEG side-chain length and grafting ratio, we observed that frictional properties of polymer-coated interfaces strongly depend on the architecture of PLL-g-PEG. Polymer-film formation and the influence of polymer architecture will be reviewed while the role of solvent and manifestation of ultra-low friction will be discussed in detail.

Onset age of L2 acquisition influences language network in early and late Cantonese-Mandarin bilinguals.

PubMed

Liu, Xiaojin; Tu, Liu; Wang, Junjing; Jiang, Bo; Gao, Wei; Pan, Ximin; Li, Meng; Zhong, Miao; Zhu, Zhenzhen; Niu, Meiqi; Li, Yanyan; Zhao, Ling; Chen, Xiaoxi; Liu, Chang; Lu, Zhi; Huang, Ruiwang

2017-11-01

Early second language (L2) experience influences the neural organization of L2 in neuro-plastic terms. Previous studies tried to reveal these plastic effects of age of second language acquisition (AoA-L2) and proficiency-level in L2 (PL-L2) on the neural basis of language processing in bilinguals. Although different activation patterns have been observed during language processing in early and late bilinguals by task-fMRI, few studies reported the effect of AoA-L2 and high PL-L2 on language network at resting state. In this study, we acquired resting-state fMRI (R-fMRI) data from 10 Cantonese (L1)-Mandarin (L2) early bilinguals (acquired L2: 3years old) and 11 late bilinguals (acquired L2: 6years old), and analyzed their topological properties of language networks after controlling the language daily exposure and usage as well as PL in L1 and L2. We found that early bilinguals had significantly a higher clustering coefficient, global and local efficiency, but significantly lower characteristic path length compared to late bilinguals. Modular analysis indicated that compared to late bilinguals, early bilinguals showed significantly stronger intra-modular functional connectivity in the semantic and phonetic modules, stronger inter-modular functional connectivity between the semantic and phonetic modules as well as between the phonetic and syntactic modules. Differences in global and local parameters may reflect different patterns of neuro-plasticity respectively for early and late bilinguals. These results suggested that different L2 experience influences topological properties of language network, even if late bilinguals achieve high PL-L2. Our findings may provide a new perspective of neural mechanisms related to early and late bilinguals. Copyright © 2017 Elsevier Inc. All rights reserved.

Cationic Surface Charge Combined with Either Vitronectin or Laminin Dictates the Evolution of Human Embryonic Stem Cells/Microcarrier Aggregates and Cell Growth in Agitated Cultures

PubMed Central

Lam, Alan Tin-Lun; Li, Jian; Chen, Allen Kuan-Liang; Reuveny, Shaul

2014-01-01

The expansion of human pluripotent stem cells (hPSC) for biomedical applications generally compels a defined, reliable, and scalable platform. Bioreactors offer a three-dimensional culture environment that relies on the implementation of microcarriers (MC), as supports for cell anchorage and their subsequent growth. Polystyrene microspheres/MC coated with adhesion-promoting extracellular matrix (ECM) protein, vitronectin (VN), or laminin (LN) have been shown to support hPSC expansion in a static environment. However, they are insufficient to promote human embryonic stem cells (hESC) seeding and their expansion in an agitated environment. The present study describes an innovative technology, consisting of a cationic charge that underlies the ECM coatings. By combining poly-L-lysine (PLL) with a coating of ECM protein, cell attachment efficiency and cell spreading are improved, thus enabling seeding under agitation in a serum-free medium. This coating combination also critically enables the subsequent formation and evolution of hPSC/MC aggregates, which ensure cell viability and generate high yields. Aggregate dimensions of at least 300 μm during early cell growth give rise to ≈15-fold expansion at 7 days' culture. Increasing aggregate numbers at a quasi-constant size of ≈300 μm indicates hESC growth within a self-regulating microenvironment. PLL+LN enables cell seeding and aggregate evolution under constant agitation, whereas PLL+VN requires an intermediate 2-day static pause to attain comparable aggregate sizes and correspondingly high expansion yields. The cells' highly reproducible bioresponse to these defined and characterized MC surface properties is universal across multiple cell lines, thus confirming the robustness of this scalable expansion process in a defined environment. PMID:24641164

Targeted polymeric micelles for siRNA treatment of experimental cancer by intravenous injection.

PubMed

Christie, R James; Matsumoto, Yu; Miyata, Kanjiro; Nomoto, Takahiro; Fukushima, Shigeto; Osada, Kensuke; Halnaut, Julien; Pittella, Frederico; Kim, Hyun Jin; Nishiyama, Nobuhiro; Kataoka, Kazunori

2012-06-26

Small interfering ribonucleic acid (siRNA) cancer therapies administered by intravenous injection require a delivery system for transport from the bloodstream into the cytoplasm of diseased cells to perform the function of gene silencing. Here we describe nanosized polymeric micelles that deliver siRNA to solid tumors and elicit a therapeutic effect. Stable multifunctional micelle structures on the order of 45 nm in size formed by spontaneous self-assembly of block copolymers with siRNA. Block copolymers used for micelle formation were designed and synthesized to contain three main features: a siRNA binding segment containing thiols, a hydrophilic nonbinding segment, and a cell-surface binding peptide. Specifically, poly(ethylene glycol)-block-poly(L-lysine) (PEG-b-PLL) comprising lysine amines modified with 2-iminothiolane (2IT) and the cyclo-Arg-Gly-Asp (cRGD) peptide on the PEG terminus was used. Modification of PEG-b-PLL with 2IT led to improved control of micelle formation and also increased stability in the blood compartment, while installation of the cRGD peptide improved biological activity. Incorporation of siRNA into stable micelle structures containing the cRGD peptide resulted in increased gene silencing ability, improved cell uptake, and broader subcellular distribution in vitro and also improved accumulation in both the tumor mass and tumor-associated blood vessels following intravenous injection into mice. Furthermore, stable and targeted micelles inhibited the growth of subcutaneous HeLa tumor models and demonstrated gene silencing in the tumor mass following treatment with antiangiogenic siRNAs. This new micellar nanomedicine could potentially expand the utility of siRNA-based therapies for cancer treatments that require intravenous injection.

U.S. EPA, Pesticide Product Label, MOGUL AG-461, 10/30/1972

EPA Pesticide Factsheets

2011-04-21

... o o -l cv o In cast' of "()Iltad, Il1lnj('d~;[I,'I\\ llli.;h "~.,, Ith l''''llt~' of \\\\'at,'r fur at I('asl 1", Illilllill's: nlll a pll~'s)(,lan. ... OSA(a~S (::-; drulll label for details) ...

50 Mbps free space direct detection laser diode optical communication system with Q = 4 PPM signaling

NASA Technical Reports Server (NTRS)

Sun, Xiaoli; Davidson, Frederic; Field, Christopher

1990-01-01

A 50 Mbps direct detection optical communication system for use in an intersatellite link was constructed with an AlGaAs laser diode transmitter and a silicon avalanche photodiode photodetector. The system used a Q = 4 PPM format. The receiver consisted of a maximum likelihood PPM detector and a timing recovery subsystem. The PPM slot clock was recovered at the receiver by using a transition detector followed by a PLL. The PPM word clock was recovered by using a second PLL whose input was derived from the presence of back-to-back PPM pulses contained in the received random PPM pulse sequences. The system achieved a bit error rate of 0.000001 at less than 50 detected signal photons/information bit. The receiver was capable of acquiring and maintaining slot and word synchronization for received signal levels greater than 20 photons/information bit, at which the receiver bit error rate was about 0.01.

Fibronectin-based multilayer thin films.

PubMed

Gand, Adeline; Tabuteau, Maud; Chat, Coline; Ladam, Guy; Atmani, Hassan; Van Tassel, Paul R; Pauthe, Emmanuel

2017-08-01

Thin films mimicking the structure and composition of the extra-cellular matrix (ECM) are potentially attractive as biomaterials for cell contacting applications. Layer-by-layer (LbL) assembly of a biological polycation, poly(l-lysine) (PLL), and a common ECM protein, fibronectin (Fn), was employed here to construct nanoscale, ECM mimicking films. Incremental film thickness and interfacial charge magnitude are observed to diminish with layer number, resulting in sub-linear film growth scaling and saturation after about 10 layers. Infrared spectroscopy and electron microscopy together reveal the formation of Fn containing aggregates, whose presence correlates with diminished charge reversal and suppressed LbL assembly. PLL-Fn films induce a significantly greater murine MC3T3-E1 pre-osteoblastic cell proliferation, while maintaining a much higher proportion of Fn in the molecular (as opposed to fibrillar) state, compared to a Fn monolayer, suggesting the enhanced Fn content of these ECM-mimicking films to significantly, and positively, affect cell behavior. Copyright © 2017 Elsevier B.V. All rights reserved.

Rapid and annealing-free self-assembly of DNA building blocks for 3D hydrogel chaperoned by cationic comb-type copolymers.

PubMed

Zhang, Zheng; Wu, Yuyang; Yu, Feng; Niu, Chaoqun; Du, Zhi; Chen, Yong; Du, Jie

2017-10-01

The construction and self-assembly of DNA building blocks are the foundation of bottom-up development of three-dimensional DNA nanostructures or hydrogels. However, most self-assembly from DNA components is impeded by the mishybridized intermediates or the thermodynamic instability. To enable rapid production of complicated DNA objects with high yields no need for annealing process, herein different DNA building blocks (Y-shaped, L- and L'-shaped units) were assembled in presence of a cationic comb-type copolymer, poly (L-lysine)-graft-dextran (PLL-g-Dex), under physiological conditions. The results demonstrated that PLL-g-Dex not only significantly promoted the self-assembly of DNA blocks with high efficiency, but also stabilized the assembled multi-level structures especially for promoting the complicated 3D DNA hydrogel formation. This study develops a novel strategy for rapid and high-yield production of DNA hydrogel even derived from instable building blocks at relatively low DNA concentrations, which would endow DNA nanotechnology for more practical applications.

Synthetic beta-solenoid proteins with the fragment-free computational design of a beta-hairpin extension

PubMed Central

MacDonald, James T.; Kabasakal, Burak V.; Godding, David; Kraatz, Sebastian; Henderson, Louie; Barber, James; Freemont, Paul S.; Murray, James W.

2016-01-01

The ability to design and construct structures with atomic level precision is one of the key goals of nanotechnology. Proteins offer an attractive target for atomic design because they can be synthesized chemically or biologically and can self-assemble. However, the generalized protein folding and design problem is unsolved. One approach to simplifying the problem is to use a repetitive protein as a scaffold. Repeat proteins are intrinsically modular, and their folding and structures are better understood than large globular domains. Here, we have developed a class of synthetic repeat proteins based on the pentapeptide repeat family of beta-solenoid proteins. We have constructed length variants of the basic scaffold and computationally designed de novo loops projecting from the scaffold core. The experimentally solved 3.56-Å resolution crystal structure of one designed loop matches closely the designed hairpin structure, showing the computational design of a backbone extension onto a synthetic protein core without the use of backbone fragments from known structures. Two other loop designs were not clearly resolved in the crystal structures, and one loop appeared to be in an incorrect conformation. We have also shown that the repeat unit can accommodate whole-domain insertions by inserting a domain into one of the designed loops. PMID:27573845

Input filter compensation for switching regulators

NASA Technical Reports Server (NTRS)

Lee, F. C.; Kelkar, S. S.

1982-01-01

The problems caused by the interaction between the input filter, output filter, and the control loop are discussed. The input filter design is made more complicated because of the need to avoid performance degradation and also stay within the weight and loss limitations. Conventional input filter design techniques are then dicussed. The concept of pole zero cancellation is reviewed; this concept is the basis for an approach to control the peaking of the output impedance of the input filter and thus mitigate some of the problems caused by the input filter. The proposed approach for control of the peaking of the output impedance of the input filter is to use a feedforward loop working in conjunction with feedback loops, thus forming a total state control scheme. The design of the feedforward loop for a buck regulator is described. A possible implementation of the feedforward loop design is suggested.

Development and Implementation of a Design Metric for Systems Containing Long-Term Fluid Loops

NASA Technical Reports Server (NTRS)

Steele, John W.

2016-01-01

John Steele, a chemist and technical fellow from United Technologies Corporation, provided a water quality module to assist engineers and scientists with a metric tool to evaluate risks associated with the design of space systems with fluid loops. This design metric is a methodical, quantitative, lessons-learned based means to evaluate the robustness of a long-term fluid loop system design. The tool was developed by a cross-section of engineering disciplines who had decades of experience and problem resolution.

The design of components for an advanced Rankine cycle test facility.

NASA Technical Reports Server (NTRS)

Bond, J. A.

1972-01-01

The design of a facility for testing components of an advanced Rankine cycle power system is summarized. The facility is a three-loop system in which lithium, potassium and NaK-78 are the working fluids of the primary, secondary and heat-rejection loops, respectively. Design bases and performance predictions for the major loop components, including the lithium heater and the potassium boiler, condenser and preheater, are outlined.

Analysis of asymmetric resonance response of thermally excited silicon micro-cantilevers for mass-sensitive nanoparticle detection

NASA Astrophysics Data System (ADS)

Bertke, Maik; Hamdana, Gerry; Wu, Wenze; Suryo Wasisto, Hutomo; Uhde, Erik; Peiner, Erwin

2017-06-01

In this paper, the asymmetric resonance frequency (f 0) responses of thermally in-plane excited silicon cantilevers for a pocket-sized, cantilever-based airborne nanoparticle detector (Cantor) are analysed. By measuring the shift of f 0 caused by the deposition of nanoparticles (NPs), the cantilevers are used as a microbalance. The cantilever sensors are low cost manufactured from silicon by bulk-micromachining techniques and contain an integrated p-type heating actuator and a sensing piezoresistive Wheatstone bridge. f 0 is tracked by a homemade phase-locked loop (PPL) for real-time measurements. To optimize the sensor performance, a new cantilever geometry was designed, fabricated and characterized by its frequency responses. The most significant characterisation parameters of our application are f 0 and the quality factor (Q), which have high influences on sensitivity and efficiency of the NP detector. Regarding the asymmetric resonance signal, a novel fitting function based on the Fano resonance replacing the conventionally used function of the simple harmonic oscillator and a method to calculate Q by its fitting parameters were developed for a quantitative evaluation. To obtain a better understanding of the resonance behaviours, we analysed the origin of the asymmetric line shapes. Therefore, we compared the frequency response of the on-chip thermal excitation with an external excitation using an in-plane piezo actuator. In correspondence to the Fano effect, we could reconstruct the measured resonance curves by coupling two signals with constant amplitude and the expected signal of the cantilever, respectively. Moreover, the phase of the measurement signal can be analysed by this method, which is important to understand the locking process of the PLL circuit. Besides the frequency analysis, experimental results and calibration measurements with different particle types are presented. Using the described analysis method, decent results to optimize a next generation of Cantor are expected.

Water Stream "Loop-the-Loop"

ERIC Educational Resources Information Center

Jefimenko, Oleg

1974-01-01

Discusses the design of a modified loop-the-loop apparatus in which a water stream is used to illustrate centripetal forces and phenomena of high-velocity hydrodynamics. Included are some procedures of carrying out lecture demonstrations. (CC)

The Inverse Optimal Control Problem for a Three-Loop Missile Autopilot

NASA Astrophysics Data System (ADS)

Hwang, Donghyeok; Tahk, Min-Jea

2018-04-01

The performance characteristics of the autopilot must have a fast response to intercept a maneuvering target and reasonable robustness for system stability under the effect of un-modeled dynamics and noise. By the conventional approach, the three-loop autopilot design is handled by time constant, damping factor and open-loop crossover frequency to achieve the desired performance requirements. Note that the general optimal theory can be also used to obtain the same gain as obtained from the conventional approach. The key idea of using optimal control technique for feedback gain design revolves around appropriate selection and interpretation of the performance index for which the control is optimal. This paper derives an explicit expression, which relates the weight parameters appearing in the quadratic performance index to the design parameters such as open-loop crossover frequency, phase margin, damping factor, or time constant, etc. Since all set of selection of design parameters do not guarantee existence of optimal control law, explicit inequalities, which are named the optimality criteria for the three-loop autopilot (OC3L), are derived to find out all set of design parameters for which the control law is optimal. Finally, based on OC3L, an efficient gain selection procedure is developed, where time constant is set to design objective and open-loop crossover frequency and phase margin as design constraints. The effectiveness of the proposed technique is illustrated through numerical simulations.

Study of Fluid Cooling Loop System in Chinese Manned Spacecraft

NASA Astrophysics Data System (ADS)

Jiang, Jun; Xu, Jiwan; Fan, Hanlin; Huang, Jiarong

2002-01-01

change. To solve the questions, a fluid cooling loop system must be applied to Chinese manned spacecraft besides other conventional thermal control methods, such as thermal control coatings, multiplayer insulation blankets, heat pipes, electro-heating adjustment temperature devices, and so on. The paper will introduce the thermal design of inner and outer fluid loop including their constitution and fundamental, etc. The capability of heat transportation and the accuracy of control temperature for the fluid loop will be evaluated and analyzed. To insure the air temperature of sealed cabins within 21+/-4, the inlet liquid temperature of condensing heat exchanger needs to be controlled within 9+/-2. To insure this, the inlet liquid temperature of middle heat exchanger needs to be controlled within 8+/-1.8. The inlet temperature point is controlled by a subsidiary loop adjusting: when the computer receives feedbacks of the deviation and the variety rate of deviation from the controlled temperature point. It drives the temperature control valve to adjust the flow flux distribution between the main loop through radiator and the subsidiary loop which isn't through radiator to control the temperature of the mixed fluid within 8+/-1.8. The paper will also introduce thermal designs of key parts in the cooling loop, such as space radiators, heat exchangers and cooling plates. Thermal simulated tests on the ground and flight tests have been performed to verify correctness of thermal designs. rational and the loop system works order. It realizes the circulation of absorbing heat dissipation to the loop and transferring it to radiator then radiating it to space. (2) loop control system controls inlet temperature of middle heat exchanger within 8+/-1.8 under various thermal cases. Thermal design of the middle heat exchanger insures inlet temperature of condensing heat within 9+/-2. Thereby, the air temperature of sealed cabins is controlled within about 21+/-4 accurately. (3) The thermal designs of the key heat exchanging parts (such as radiator, heat exchangers and cooling plates) in the cooling loop are rational and effective, they meet the requirements of heat exchanging and assure the entire system work order.

Measurement of high-resolution mechanical contraction of cardiac muscle by induced eddy current.

PubMed

Lee, Young-Jae; Lee, Kang-Hwi; Kang, Seung-Jin; Kim, Kyeung-Nam; Khang, Seonah; Koo, Hye Ran; Gi, Sunok; Lee, Joo Hyeon; Lee, Jeong-Whan

2014-01-01

There are many types of devices which help to manage a personal health conditions such as heartbeat chest belt, pedometer and smart watch. And the most common device has the relationship with heart rate or ECG data. However, users have to attach some electrode or fasten the belt on the bare skin to measure bio-signal information. Therefore, most of people want more convenient and short-ready-time and no-need to attach electrode. In this paper, we proposed the high-resolution measuring system of mechanical activity of cardiac muscle and thereby measure heartbeat. The principle of the proposed measuring method is that the alternating current generate alternating magnetic field around coil. This primary magnetic field induces eddy current which makes magnetic field against primary coil in the nearby objects. To measure high-resolution changes of the induced secondary magnetic fields, we used digital Phase-locked loop(PLL) circuit which provides more high-resolution traces of frequency changes than the previous studies based on digital frequency counter method. As a result of our preliminary experiment, peak-peak intervals of the proposed method showed high correlation with R-R intervals of clinical ECG signals(r=0.9249). Also, from signal traces of the proposed method, we might make a conjecture that the contraction of atrium or ventricle is reflected by changing conductivity of cardiac muscle which is beating ceaselessly.

Gas spectroscopy system with transmitters and receivers in SiGe BiCMOS for 225-273 GHz

NASA Astrophysics Data System (ADS)

Schmalz, Klaus; Rothbart, Nick; Borngräber, Johannes; Yilmaz, Selahattin Berk; Kissinger, Dietmar; Hübers, Heinz-Wilhelm

2017-10-01

This paper updates results of our work on gas spectroscopy based on transmitters (TXs) and receivers (RXs) in IHP's 0.13 μm SiGe BiCMOS technology. The improved performance of our system is shown by the absorption spectra of gaseous methanol in the range 241 - 242 GHz at 1.4 Pa, corresponding to an absorption line width of about 1 MHz. The signal-noise ratio (SNR) for the absorption line of methanol at 241.7 GHz is used as measure. The system includes two fractional-n phase-locked loops (PLLs), which allow frequency ramps for the TX and RX, and a superimposed frequency shift keying modulation (FSK) for the TX. Another option includes reference frequency ramps for the PLLs in integer-n mode, which are realized by a direct digital synthesizer (DDS). An SNR of 1515 is observed for the 241.7 GHz absorption line at 1.4 Pa. We extend our single band TX/RX system with the range 238 - 252 GHz to a multi-band system to cover the range 225 - 273 GHz. It is built by combining corresponding pairs of TXs and RXs of three frequency bands in this range. The multi-band operation allows parallel spectra acquisition for these bands. For the TXs and RXs appropriate frequency ramps are generated by their external fractional-n PLL devices.

A 2.4 GHz ULP reconfigurable asymmetric transceiver for single-chip wireless neural recording IC.

PubMed

Tan, Jun; Liew, Wen-Sin; Heng, Chun-Huat; Lian, Yong

2014-08-01

This paper presents a 2.4 GHz ultra-low-power (ULP) reconfigurable asymmetric transceiver and demonstrates its application in wireless neural recording. Fabricated in 0.13 μm CMOS technology, the transceiver is optimized for sensor-gateway communications within a star-shaped network, and supports both the sensor and gateway operation modes. Binary phase-shift keying (BPSK) modulation with high data rate (DR) of 1 to 8 Mbps is used in the uplink from sensor to gateway, while on-off keying (OOK) modulation with low DR of 100 kbps is adopted in the downlink. A fully integrated Class-E PA with moderate output power has also been proposed and achieves power efficiency of 53%. To minimize area usage, inductor reuse is adopted between PA and LNA, and eliminates the need of lossy T/R switch in the RF signal path. When used as sensor, the transceiver with frequency locked phase-locked loop (PLL) achieves TX (BPSK) power efficiency of 28% @ 0 dBm output power, and RX (OOK) sensitivity of -80 dBm @ 100 kbps while consuming only 780 μW . When configured as gateway, the transceiver achieves sensitivity levels of -92, -84.5, and -77 dBm for 1, 5, and 8 Mbps BPSK, respectively. The transceiver is integrated with an 8-channel neural recording front-end, and neural signals from a rat are captured to verify the system functionality.

Investigation of air transportation technology at Ohio University, 1980. [general aviation aircraft and navigation aids

NASA Technical Reports Server (NTRS)

Mcfarland, R. H.

1981-01-01

Specific configurations of first and second order all digital phase locked loops were analyzed for both ideal and additive gaussian noise inputs. In addition, a design for a hardware digital phase locked loop capable of either first or second order operation was evaluated along with appropriate experimental data obtained from testing of the hardware loop. All parameters chosen for the analysis and the design of the digital phase locked loop were consistent with an application to an Omega navigation receiver although neither the analysis nor the design are limited to this application. For all cases tested, the experimental data showed close agreement with the analytical results indicating that the Markov chain model for first and second order digital phase locked loops are valid.

Three-phase Four-leg Inverter LabVIEW FPGA Control Code

DOE Office of Scientific and Technical Information (OSTI.GOV)

In the area of power electronics control, Field Programmable Gate Arrays (FPGAs) have the capability to outperform their Digital Signal Processor (DSP) counterparts due to the FPGA’s ability to implement true parallel processing and therefore facilitate higher switching frequencies, higher control bandwidth, and/or enhanced functionality. National Instruments (NI) has developed two platforms, Compact RIO (cRIO) and Single Board RIO (sbRIO), which combine a real-time processor with an FPGA. The FPGA can be programmed with a subset of the well-known LabVIEW graphical programming language. The use of cRIO and sbRIO for power electronics control has developed over the last few yearsmore » to include control of three-phase inverters. Most three-phase inverter topologies include three switching legs. The addition of a fourth-leg to natively generate the neutral connection allows the inverter to serve single-phase loads in a microgrid or stand-alone power system and to balance the three-phase voltages in the presence of significant load imbalance. However, the control of a four-leg inverter is much more complex. In particular, instead of standard two-dimensional space vector modulation (SVM), the inverter requires three-dimensional space vector modulation (3D-SVM). The candidate software implements complete control algorithms in LabVIEW FPGA for a three-phase four-leg inverter. The software includes feedback control loops, three-dimensional space vector modulation gate-drive algorithms, advanced alarm handling capabilities, contactor control, power measurements, and debugging and tuning tools. The feedback control loops allow inverter operation in AC voltage control, AC current control, or DC bus voltage control modes based on external mode selection by a user or supervisory controller. The software includes the ability to synchronize its AC output to the grid or other voltage-source before connection. The software also includes provisions to allow inverter operation in parallel with other voltage regulating devices on the AC or DC buses. This flexibility allows the Inverter to operate as a stand-alone voltage source, connected to the grid, or in parallel with other controllable voltage sources as part of a microgrid or remote power system. In addition, as the inverter is expected to operate under severe unbalanced conditions, the software includes algorithms to accurately compute real and reactive power for each phase based on definitions provided in the IEEE Standard 1459: IEEE Standard Definitions for the Measurement of Electric Power Quantities Under Sinusoidal, Nonsinusoidal, Balanced, or Unbalanced Conditions. Finally, the software includes code to output analog signals for debugging and for tuning of control loops. The software fits on the Xilinx Virtex V LX110 FPGA embedded in the NI cRIO-9118 FPGA chassis, and with a 40 MHz base clock, supports a modulation update rate of 40 MHz, user-settable switching frequencies and synchronized control loop update rates of tens of kHz, and reference waveform generation, including Phase Lock Loop (PLL), update rate of 100 kHz.« less

Novel design methods for magnetic flux loops in the National Compact Stellarator Experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pomphrey, N.; Lazarus, E.; Zarnstorff, M.

2007-05-15

Magnetic pickup loops on the vacuum vessel (VV) can provide an abundance of equilibrium information for stellarators. A substantial effort has gone into designing flux loops for the National Compact Stellarator Experiment (NCSX) [Zarnstorff et al., Plasma Phys. Controlled Fusion 43, A237 (2001)], a three-field period quasi-axisymmetric stellarator under construction at the Princeton Plasma Physics Laboratory. The design philosophy, to measure all of the magnetic field distributions normal to the VV that can be measured, has necessitated the development of singular value decomposition algorithms for identifying efficient loop locations. Fields are expected to be predominantly stellarator symmetric (SS)--the symmetry ofmore » the machine design--with toroidal mode numbers per torus (n) equal to a multiple of 3 and possessing reflection symmetry in a period. However, plasma instabilities and coil imperfections will generate non-SS fields that must also be diagnosed. The measured symmetric fields will yield important information on the plasma current and pressure profile as well as on the plasma shape. All fields that obey the design symmetries could be measured by placing flux loops in a single half-period of the VV, but accurate resolution of nonsymmetric modes, quantified by the condition number of a matrix, requires repositioning loops to equivalent locations on the full torus. A subarray of loops located along the inside wall of the vertically elongated cross section was designed to detect n=3, m=5 or 6 resonant field perturbations that can cause important islands. Additional subarrays included are continuous in the toroidal and poloidal directions. Loops are also placed at symmetry points of the VV to obtain maximal sensitivity to asymmetric perturbations. Combining results from various calculations which have made extensive use of a database of 2500 free-boundary VMEC equilibria, has led to the choice of 225 flux loops for NCSX, of which 151 have distinct shapes.« less

Experimental design for three-color and four-color gene expression microarrays.

PubMed

Woo, Yong; Krueger, Winfried; Kaur, Anupinder; Churchill, Gary

2005-06-01

Three-color microarrays, compared with two-color microarrays, can increase design efficiency and power to detect differential expression without additional samples and arrays. Furthermore, three-color microarray technology is currently available at a reasonable cost. Despite the potential advantages, clear guidelines for designing and analyzing three-color experiments do not exist. We propose a three- and a four-color cyclic design (loop) and a complementary graphical representation to help design experiments that are balanced, efficient and robust to hybridization failures. In theory, three-color loop designs are more efficient than two-color loop designs. Experiments using both two- and three-color platforms were performed in parallel and their outputs were analyzed using linear mixed model analysis in R/MAANOVA. These results demonstrate that three-color experiments using the same number of samples (and fewer arrays) will perform as efficiently as two-color experiments. The improved efficiency of the design is somewhat offset by a reduced dynamic range and increased variability in the three-color experimental system. This result suggests that, with minor technological improvements, three-color microarrays using loop designs could detect differential expression more efficiently than two-color loop designs. http://www.jax.org/staff/churchill/labsite/software Multicolor cyclic design construction methods and examples along with additional results of the experiment are provided at http://www.jax.org/staff/churchill/labsite/pubs/yong.

A new design approach to innovative spectrometers. Case study: TROPOLITE

NASA Astrophysics Data System (ADS)

Volatier, Jean-Baptiste; Baümer, Stefan; Kruizinga, Bob; Vink, Rob

2014-05-01

Designing a novel optical system is a nested iterative process. The optimization loop, from a starting point to final system is already mostly automated. However this loop is part of a wider loop which is not. This wider loop starts with an optical specification and ends with a manufacturability assessment. When designing a new spectrometer with emphasis on weight and cost, numerous iterations between the optical- and mechanical designer are inevitable. The optical designer must then be able to reliably produce optical designs based on new input gained from multidisciplinary studies. This paper presents a procedure that can automatically generate new starting points based on any kind of input or new constraint that might arise. These starting points can then be handed over to a generic optimization routine to make the design tasks extremely efficient. The optical designer job is then not to design optical systems, but to meta-design a procedure that produces optical systems paving the way for system level optimization. We present here this procedure and its application to the design of TROPOLITE a lightweight push broom imaging spectrometer.

Ground Source Heat Pump Sub-Slab Heat Exchange Loop Performance in a Cold Climate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mittereder, N.; Poerschke, A.

2013-11-01

This report presents a cold-climate project that examines an alternative approach to ground source heat pump (GSHP) ground loop design. The innovative ground loop design is an attempt to reduce the installed cost of the ground loop heat exchange portion of the system by containing the entire ground loop within the excavated location beneath the basement slab. Prior to the installation and operation of the sub-slab heat exchanger, energy modeling using TRNSYS software and concurrent design efforts were performed to determine the size and orientation of the system. One key parameter in the design is the installation of the GSHPmore » in a low-load home, which considerably reduces the needed capacity of the ground loop heat exchanger. This report analyzes data from two cooling seasons and one heating season. Upon completion of the monitoring phase, measurements revealed that the initial TRNSYS simulated horizontal sub-slab ground loop heat exchanger fluid temperatures and heat transfer rates differed from the measured values. To determine the cause of this discrepancy, an updated model was developed utilizing a new TRNSYS subroutine for simulating sub-slab heat exchangers. Measurements of fluid temperature, soil temperature, and heat transfer were used to validate the updated model.« less

Conceptual design of a thermalhydraulic loop for multiple test geometries at supercritical conditions named Supercritical Phenomena Experimental Test Apparatus (SPETA)

NASA Astrophysics Data System (ADS)

Adenariwo, Adepoju

The efficiency of nuclear reactors can be improved by increasing the operating pressure of current nuclear reactors. Current CANDU-type nuclear reactors use heavy water as coolant at an outlet pressure of up to 11.5 MPa. Conceptual SuperCritical Water Reactors (SCWRs) will operate at a higher coolant outlet pressure of 25 MPa. Supercritical water technology has been used in advanced coal plants and its application proves promising to be employed in nuclear reactors. To better understand how supercritical water technology can be applied in nuclear power plants, supercritical water loops are used to study the heat transfer phenomena as it applies to CANDU-type reactors. A conceptual design of a loop known as the Supercritical Phenomena Experimental Apparatus (SPETA) has been done. This loop has been designed to fit in a 9 m by 2 m by 2.8 m enclosure that will be installed at the University of Ontario Institute of Technology Energy Research Laboratory. The loop include components to safely start up and shut down various test sections, produce a heat source to the test section, and to remove reject heat. It is expected that loop will be able to investigate the behaviour of supercritical water in various geometries including bare tubes, annulus tubes, and multi-element-type bundles. The experimental geometries are designed to match the fluid properties of Canadian SCWR fuel channel designs so that they are representative of a practical application of supercritical water technology in nuclear plants. This loop will investigate various test section orientations which are the horizontal, vertical, and inclined to investigate buoyancy effects. Frictional pressure drop effects and satisfactory methods of estimating hydraulic resistances in supercritical fluid shall also be estimated with the loop. Operating limits for SPETA have been established to be able to capture the important heat transfer phenomena at supercritical conditions. Heat balance and flow calculations have been done to appropriately size components in the loop. Sensitivity analysis has been done to find the optimum design for the loop.

Molecular Velcro constructed from polymer loop brushes showing enhanced adhesion force

NASA Astrophysics Data System (ADS)

Zhou, Tian; Han, Biao; Han, Lin; Li, Christopher; Department of Materials Science; Engineering Team; School of Biomedical Engineering, Science; Health Systems Team

2015-03-01

Molecular Velcro is commonly seen in biological systems as the formation of strong physical entanglement at molecular scale could induce strong adhesion, which is crucial to many biological processes. To mimic this structure, we designed, and fabricated polymer loop brushes using polymer single crystals with desired surface functionality and controlled chain folding. Compared with reported loop brushes fabricated using triblock copolymers, the present loop bushes have precise loop sizes, loop grafting density, and well controlled tethering locations on the solid surface. Atomic force microscopy-based force spectroscopy measurements using a polymer chain coated probe reveal that the adhesion force are significantly enhanced on the loop brush surface as compared with its single-strand counterpart. This study directly shows the effect of polymer brush conformation on their properties, and suggests a promising strategy for advanced polymer surface design.

Two-Stage Design Method for Enhanced Inductive Energy Transmission with Q-Constrained Planar Square Loops.

PubMed

Eteng, Akaa Agbaeze; Abdul Rahim, Sharul Kamal; Leow, Chee Yen; Chew, Beng Wah; Vandenbosch, Guy A E

2016-01-01

Q-factor constraints are usually imposed on conductor loops employed as proximity range High Frequency Radio Frequency Identification (HF-RFID) reader antennas to ensure adequate data bandwidth. However, pairing such low Q-factor loops in inductive energy transmission links restricts the link transmission performance. The contribution of this paper is to assess the improvement that is reached with a two-stage design method, concerning the transmission performance of a planar square loop relative to an initial design, without compromise to a Q-factor constraint. The first stage of the synthesis flow is analytical in approach, and determines the number and spacing of turns by which coupling between similar paired square loops can be enhanced with low deviation from the Q-factor limit presented by an initial design. The second stage applies full-wave electromagnetic simulations to determine more appropriate turn spacing and widths to match the Q-factor constraint, and achieve improved coupling relative to the initial design. Evaluating the design method in a test scenario yielded a more than 5% increase in link transmission efficiency, as well as an improvement in the link fractional bandwidth by more than 3%, without violating the loop Q-factor limit. These transmission performance enhancements are indicative of a potential for modifying proximity HF-RFID reader antennas for efficient inductive energy transfer and data telemetry links.

U.S. EPA, Pesticide Product Label, TCIPN, 04/15/1994

EPA Pesticide Factsheets

2011-04-21

... on 7 to 10 dy Intorv ... or e. noe ••• ory to control dI ..... 2" to 2" pll.lnitill. ... che_ pr .... r. i ••• vera. Com (Sw ••• ) 'or fr •• h merke' and Field grown 'or •• ed ...

Loran-C flight test software

NASA Technical Reports Server (NTRS)

Nickum, J. D.

1978-01-01

The software package developed for the KIM-1 Micro-System and the Mini-L PLL receiver to simplify taking flight test data is described along with the address and data bus buffers used in the KIM-1 Micro-system. The interface hardware and timing are also presented to describe completely the software programs.

Interactions of Graphene Oxide Nanomaterials with Natural Organic Matter and Metal Oxide Surfaces

EPA Science Inventory

Interactions of graphene oxide (GO) with silica surfaces were investigated using a quartz crystal microbalance with dissipation monitoring (QCM-D). Both GO deposition and release were monitored on silica- and poly-l-lysine (PLL) coated surfaces as a function of GO concentration a...

Preliminary demonstration of a robust controller design method

NASA Technical Reports Server (NTRS)

Anderson, L. R.

1980-01-01

Alternative computational procedures for obtaining a feedback control law which yields a control signal based on measurable quantitites are evaluated. The three methods evaluated are: (1) the standard linear quadratic regulator design model; (2) minimization of the norm of the feedback matrix, k via nonlinear programming subject to the constraint that the closed loop eigenvalues be in a specified domain in the complex plane; and (3) maximize the angles between the closed loop eigenvectors in combination with minimizing the norm of K also via the constrained nonlinear programming. The third or robust design method was chosen to yield a closed loop system whose eigenvalues are insensitive to small changes in the A and B matrices. The relationship between orthogonality of closed loop eigenvectors and the sensitivity of closed loop eigenvalues is described. Computer programs are described.

High resolution angular sensor. [reducing ring laser gyro output quantization using phase locked loops

NASA Technical Reports Server (NTRS)

Gneses, M. I.; Berg, D. S.

1981-01-01

Specifications for the pointing stabilization system of the large space telescope were used in an investigation of the feasibility of reducing ring laser gyro output quantization to the sub-arc-second level by the use of phase locked loops and associated electronics. Systems analysis procedures are discussed and a multioscillator laser gyro model is presented along with data on the oscillator noise. It is shown that a second order closed loop can meet the measurement noise requirements when the loop gain and time constant of the loop filter are appropriately chosen. The preliminary electrical design is discussed from the standpoint of circuit tradeoff considerations. Analog, digital, and hybrid designs are given and their applicability to the high resolution sensor is examined. the electrical design choice of a system configuration is detailed. The design and operation of the various modules is considered and system block diagrams are included. Phase 1 and 2 test results using the multioscillator laser gyro are included.

Closed Loop System Identification with Genetic Algorithms

NASA Technical Reports Server (NTRS)

Whorton, Mark S.

2004-01-01

High performance control design for a flexible space structure is challenging since high fidelity plant models are di.cult to obtain a priori. Uncertainty in the control design models typically require a very robust, low performance control design which must be tuned on-orbit to achieve the required performance. Closed loop system identi.cation is often required to obtain a multivariable open loop plant model based on closed-loop response data. In order to provide an accurate initial plant model to guarantee convergence for standard local optimization methods, this paper presents a global parameter optimization method using genetic algorithms. A minimal representation of the state space dynamics is employed to mitigate the non-uniqueness and over-parameterization of general state space realizations. This control-relevant system identi.cation procedure stresses the joint nature of the system identi.cation and control design problem by seeking to obtain a model that minimizes the di.erence between the predicted and actual closed-loop performance.

Analysis and design of a 3rd order velocity-controlled closed-loop for MEMS vibratory gyroscopes.

PubMed

Wu, Huan-ming; Yang, Hai-gang; Yin, Tao; Jiao, Ji-wei

2013-09-18

The time-average method currently available is limited to analyzing the specific performance of the automatic gain control-proportional and integral (AGC-PI) based velocity-controlled closed-loop in a micro-electro-mechanical systems (MEMS) vibratory gyroscope, since it is hard to solve nonlinear functions in the time domain when the control loop reaches to 3rd order. In this paper, we propose a linearization design approach to overcome this limitation by establishing a 3rd order linear model of the control loop and transferring the analysis to the frequency domain. Order reduction is applied on the built linear model's transfer function by constructing a zero-pole doublet, and therefore mathematical expression of each control loop's performance specification is obtained. Then an optimization methodology is summarized, which reveals that a robust, stable and swift control loop can be achieved by carefully selecting the system parameters following a priority order. Closed-loop drive circuits are designed and implemented using 0.35 μm complementary metal oxide semiconductor (CMOS) process, and experiments carried out on a gyroscope prototype verify the optimization methodology that an optimized stability of the control loop can be achieved by constructing the zero-pole doublet, and disturbance rejection capability (D.R.C) of the control loop can be improved by increasing the integral term.

Trajectory tracking control for underactuated stratospheric airship

NASA Astrophysics Data System (ADS)

Zheng, Zewei; Huo, Wei; Wu, Zhe

2012-10-01

Stratospheric airship is a new kind of aerospace system which has attracted worldwide developing interests for its broad application prospects. Based on the trajectory linearization control (TLC) theory, a novel trajectory tracking control method for an underactuated stratospheric airship is presented in this paper. Firstly, the TLC theory is described sketchily, and the dynamic model of the stratospheric airship is introduced with kinematics and dynamics equations. Then, the trajectory tracking control strategy is deduced in detail. The designed control system possesses a cascaded structure which consists of desired attitude calculation, position control loop and attitude control loop. Two sub-loops are designed for the position and attitude control loops, respectively, including the kinematics control loop and dynamics control loop. Stability analysis shows that the controlled closed-loop system is exponentially stable. Finally, simulation results for the stratospheric airship to track typical trajectories are illustrated to verify effectiveness of the proposed approach.

An Innovative Hybrid Loop-Pool SFR Design and Safety Analysis Methods: Today and Tomorrow

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hongbin Zhang; Haihua Zhao; Vincent Mousseau

2008-04-01

Investment in commercial sodium cooled fast reactor (SFR) power plants will become possible only if SFRs achieve economic competitiveness as compared to light water reactors and other Generation IV reactors. Toward that end, we have launched efforts to improve the economics and safety of SFRs from the thermal design and safety analyses perspectives at Idaho National Laboratory. From the thermal design perspective, an innovative hybrid loop-pool SFR design has been proposed. This design takes advantage of the inherent safety of a pool design and the compactness of a loop design to further improve economics and safety. From the safety analysesmore » perspective, we have initiated an effort to develop a high fidelity reactor system safety code.« less

A linear quadratic Gaussian with loop transfer recovery proximity operations autopilot for spacecraft. M.S. Thesis - MIT

NASA Technical Reports Server (NTRS)

Chen, George T.

1987-01-01

An automatic control scheme for spacecraft proximity operations is presented. The controller is capable of holding the vehicle at a prescribed location relative to a target, or maneuvering it to a different relative position using straight line-of-sight translations. The autopilot uses a feedforward loop to initiate and terminate maneuvers, and for operations at nonequilibrium set-points. A multivariate feedback loop facilitates precise position and velocity control in the presence of sensor noise. The feedback loop is formulated using the Linear Quadratic Gaussian (LQG) with Loop Transfer Recovery (LTR) design procedure. Linear models of spacecraft dynamics, adapted from Clohessey-Wiltshire Equations, are augmented and loop shaping techniques are applied to design a target feedback loop. The loop transfer recovery procedure is used to recover the frequency domain properties of the target feedback loop. The resulting compensator is integrated into an autopilot which is tested in a high fidelity Space Shuttle Simulator. The autopilot performance is evaluated for a variety of proximity operations tasks envisioned for future Shuttle flights.

On higher order discrete phase-locked loops.

NASA Technical Reports Server (NTRS)

Gill, G. S.; Gupta, S. C.

1972-01-01

An exact mathematical model is developed for a discrete loop of a general order particularly suitable for digital computation. The deterministic response of the loop to the phase step and the frequency step is investigated. The design of the digital filter for the second-order loop is considered. Use is made of the incremental phase plane to study the phase error behavior of the loop. The model of the noisy loop is derived and the optimization of the loop filter for minimum mean-square error is considered.

A control system design approach for flexible spacecraft

NASA Technical Reports Server (NTRS)

Silverberg, L. M.

1985-01-01

A control system design approach for flexible spacecraft is presented. The control system design is carried out in two steps. The first step consists of determining the ideal control system in terms of a desirable dynamic performance. The second step consists of designing a control system using a limited number of actuators that possess a dynamic performance that is close to the ideal dynamic performance. The effects of using a limited number of actuators is that the actual closed-loop eigenvalues differ from the ideal closed-loop eigenvalues. A method is presented to approximate the actual closed-loop eigenvalues so that the calculation of the actual closed-loop eigenvalues can be avoided. Depending on the application, it also may be desirable to apply the control forces as impulses. The effect of digitizing the control to produce the appropriate impulses is also examined.

Digital Phase-Locked Loop With Phase And Frequency Feedback

NASA Technical Reports Server (NTRS)

Thomas, J. Brooks

1991-01-01

Advanced design for digital phase-lock loop (DPLL) allows loop gains higher than those used in other designs. Divided into two major components: counterrotation processor and tracking processor. Notable features include use of both phase and rate-of-change-of-phase feedback instead of frequency feedback alone, normalized sine phase extractor, improved method for extracting measured phase, and improved method for "compressing" output rate.

FY 2017-Progress Report on the Design and Construction of the Sodium Loop SMT-3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Natesan, K.; Momozaki, Y.

This report provides an update on the design of a forced-convection sodium loop to be used for the evaluation of sodium compatibility of advanced Alloy 709 with emphasis on long term exposures of tensile, creep, fatigue, creep fatigue, and fracture toughness ASTM-size specimens in support of ASME Code qualification and NRC licensing. The report is a deliverable (Level 4) in FY17 (M4AT-17AN1602094), under the Work Package AT-17AN160209, “Sodium Compatibility” performed by Argonne National Laboratory (ANL), as part of the Advanced Materials Program for the Advanced Reactor Technology. This work package enables the development of advanced structural materials by providing corrosion,more » microstructure, and mechanical property data from the standpoint of sodium compatibility of advanced structural alloys. The first sodium loop (SMT-1) with a single tank was constructed in 2011 at ANL and has been in operation for exposure of subsize sheet specimens of advanced alloys at a single temperature. The second sodium loop with dual tanks (SMT-2) was constructed in 2013 and has been in operation for the exposure of subsize sheet specimens of advanced alloys at two different temperatures. The current loop (SMT-3) has been designed to incorporate sufficient chamber capacity to expose a large number of ASTM-size specimens to evaluate the sodium effects on tensile, creep, fatigue, creep-fatigue, and fracture toughness properties, in support of ASME Code Qualification and USNRC Licensing. The design of individual components for the third sodium loop SMT-3 is almost complete. The design also has been sent to an outside vendor for piping analysis to be in compliance with ASME Code. A purchase order has been placed with an outside vendor for the fabrication of major components such as the specimen exposure tanks. However, we have contracted with another vendor to establish the piping design in compliance with ASME design codes. The piping design was completed in FY2017 and the information is being transmitted to the tank fabricator. The SMT-3 loop will be located in Building 206 adjacent to the currently operating SMT-2 loop. In addition, we have demolished the aged power supply system in Building 206 and installed a new transformer, wiring, and power panels for the new loop. Procurement of some of the long lead items such as valves, EM pumps, EM flowmeters, etc. is in progress and will continue in FY 2018. The construction of components such as cold trap, economizers, piping arrangement etc. will be performed in the central shops at ANL. About 150 liters of sodium for the loop will be procured in early FY2018. The loop system is designed to circulate sodium through the sample tanks and the associated loop without an operator for an extended period of time. With the three sodium loops (with single-tank, dual-tank and four–tanks), materials can be tested at different sodium temperatures, and large tensile, creep, fatigue, creep-fatigue, and fracture toughness specimens can be exposed to sodium for extended periods of time and generate data on mechanical properties in support of ASME Code Qualification and USNRC Licensing of advanced Alloy 709 for use as a structural material in SFRs.« less

Degradation and Characterization of Antimisting Kerosene (AMK).

DTIC Science & Technology

1982-12-01

EXECUTIVE SUMMARY ................................................... I. INTRODUCTION ............................................... 2 II. DEGRADER...P - density Pll-P22 - normal stress difference P12 - shear stress x EXECUTIVE SI-9ARY CSingle pass degradation of Antinmisting Kerosene (ANIK) has...While the jet thrust experiment is more difficult to execute and interpret than flow experiments, a quality control test based on normal stresses would

Molecular dynamics simulations of DNA-polycation complexes

NASA Astrophysics Data System (ADS)

Ziebarth, Jesse; Wang, Yongmei

2008-03-01

A necessary step in the preparation of DNA for use in gene therapy is the packaging of DNA with a vector that can condense DNA and provide protection from degrading enzymes. Because of the immunoresponses caused by viral vectors, there has been interest in developing synthetic gene therapy vectors, with polycations emerging as promising candidates. Molecular dynamics simulations of the DNA duplex CGCGAATTCGCG in the presence of 20 monomer long sequences of the polycations, poly-L-lysine (PLL) and polyethyleneimine (PEI), with explicit counterions and TIP3P water, are performed to provide insight into the structure and formation of DNA polyplexes. After an initial separation of approximately 50 å, the DNA and polycation come together and form a stable complex within 10 ns. The DNA does not undergo any major structural changes upon complexation and remains in the B-form. In the formed complex, the charged amine groups of the polycation mainly interact with DNA phosphate groups, and rarely occupy electronegative sites in either the major or minor grooves. Differences between complexation with PEI and PLL will be discussed.

Heart Rate Detection During Sleep Using a Flexible RF Resonator and Injection-Locked PLL Sensor.

PubMed

Kim, Sung Woo; Choi, Soo Beom; An, Yong-Jun; Kim, Byung-Hyun; Kim, Deok Won; Yook, Jong-Gwan

2015-11-01

Novel nonintrusive technologies for wrist pulse detection have been developed and proposed as systems for sleep monitoring using three types of radio frequency (RF) sensors. The three types of RF sensors for heart rate measurement on wrist are a flexible RF single resonator, array resonators, and an injection-locked PLL resonator sensor. To verify the performance of the new RF systems, we compared heart rates between presleep time and postsleep onset time. Heart rates of ten subjects were measured using the RF systems during sleep. All three RF devices detected heart rates at 0.2 to 1 mm distance from the skin of the wrist over clothes made of cotton fabric. The wrist pulse signals of a flexible RF single resonator were consistent with the signals obtained by a portable piezoelectric transducer as a reference. Then, we confirmed that the heart rate after sleep onset time significantly decreased compared to before sleep. In conclusion, the RF system can be utilized as a noncontact nonintrusive method for measuring heart rates during sleep.

Factors Affecting the Nonlinear Force Versus Distraction Height Curves in an In Vitro C5-C6 Anterior Cervical Distraction Model.

PubMed

Wen, Junxiang; Xu, Jianwei; Li, Lijun; Yang, Mingjie; Pan, Jie; Chen, Deyu; Jia, Lianshun; Tan, Jun

2017-06-01

In vitro biomechanical study of cervical intervertebral distraction. To investigate the forces required for distraction to different heights in an in vitro C5-C6 anterior cervical distraction model, focusing on the influence of the intervertebral disk, posterior longitudinal ligament (PLL), and ligamentum flavum (LF). No previous studies have reported on the forces required for distraction to various heights or the factors resisting distraction in anterior cervical discectomy and fusion. Anterior cervical distraction at C5-C6 was performed in 6 cadaveric specimens using a biomechanical testing machine, under 4 conditions: A, before disk removal; B, after disk removal; C, after disk and PLL removal; and D, after disk and PLL removal and cutting of the LF. Distraction was performed from 0 to 10 mm at a constant velocity (5 mm/min). Force and distraction height were recorded automatically. The force required increased with distraction height under all 4 conditions. There was a sudden increase in force required at 6-7 mm under conditions B and C, but not D. Under condition A, distraction to 5 mm required a force of 268.3±38.87 N. Under conditions B and C, distraction to 6 mm required <15 N, and further distraction required dramatically increased force, with distraction to 10 mm requiring 115.4±10.67 and 68.4±9.67 N, respectively. Under condition D, no marked increase in force was recorded. Distraction of the intervertebral space was much easier after disk removal. An intact LF caused a sudden marked increase in the force required for distraction, possibly indicating the point at which the LF was fully stretched. This increase in resistance may help to determine the optimal distraction height to avoid stress to the endplate spacer.

Development of a Remodeled Caspar Retractor and Its Application in the Measurement of Distractive Resistance in an In Vitro Anterior Cervical Distraction Model.

PubMed

Wen, Junxiang; Xu, Jianwei; Li, Lijun; Yang, Mingjie; Pan, Jie; Chen, Deyu; Jia, Lianshun; Tan, Jun

2017-06-01

In vitro biomechanical study of the cervical intervertebral distraction using a remodeled Caspar retractor. To investigate the torques required for distraction to different heights in an in vitro C3-C4 anterior cervical distraction model using a remodeled Caspar retractor, focusing on the influence of the intervertebral disk, posterior longitudinal ligament (PLL), and ligamentum flavum (LF). No previous studies have reported on the torques required for distraction to various heights or the factors resisting distraction in anterior cervical discectomy and fusion. Anterior cervical distractions at C3-C4 was performed in 6 cadaveric specimens using a remodeled Caspar retractor, under 4 conditions: A, before disk removal; B, after disk removal; C, after disk and PLL removal; and D, after disk and PLL removal and cutting of the LF. Distraction was performed for 5 teeth, and distractive torque of each tooth was recorded. The torque increased with distraction height under all conditions. There was a sudden increase in torque at the fourth tooth under conditions B and C, but not D. Under condition A, distraction to the third tooth required 84.8±13.3 cN m. Under conditions B and C, distraction to the third tooth required <13 cN m, and further distraction required dramatically increased torque. Under condition D, no marked increase in torque was recorded. Distraction of the intervertebral space was much easier after disk removal. An intact LF caused a sudden marked increase in the force required for distraction, possibly indicating the point at which the LF was fully stretched. This increase in resistance may help to determine the optimal distraction height to avoid excessive stress to the endplate spacer. The remodeled Caspar retractor in the present study may provide a feasible and convenient method for intraoperative measurement of distractive resistance.

Multivariable control of the Space Shuttle Remote Manipulator System using linearization by state feedback. M.S. Thesis

NASA Technical Reports Server (NTRS)

Gettman, Chang-Ching LO

1993-01-01

This thesis develops and demonstrates an approach to nonlinear control system design using linearization by state feedback. The design provides improved transient response behavior allowing faster maneuvering of payloads by the SRMS. Modeling uncertainty is accounted for by using a second feedback loop designed around the feedback linearized dynamics. A classical feedback loop is developed to provide the easy implementation required for the relatively small on board computers. Feedback linearization also allows the use of higher bandwidth model based compensation in the outer loop, since it helps maintain stability in the presence of the nonlinearities typically neglected in model based designs.

Investigation of Inner Loop Flight Control Strategies for High-Speed Research

NASA Technical Reports Server (NTRS)

Newman, Brett; Kassem, Ayman

1999-01-01

This report describes the activities and findings conducted under contract NAS1-19858 with NASA Langley Research Center. Subject matter is the investigation of suitable flight control design methodologies and solutions for large, flexible high-speed vehicles. Specifically, methodologies are to address the inner control loops used for stabilization and augmentation of a highly coupled airframe system possibly involving rigid-body motion, structural vibrations, unsteady aerodynamics, and actuator dynamics. Techniques considered in this body of work are primarily conventional-based, and the vehicle of interest is the High-Speed Civil Transport (HSCT). Major findings include 1) current aeroelastic vehicle modeling procedures require further emphasis and refinement, 2) traditional and nontraditional inner loop flight control strategies employing a single feedback loop do not appear sufficient for highly flexible HSCT class vehicles, 3) inner loop flight control systems will, in all likelihood, require multiple interacting feedback loops, and 4) Ref. H HSCT configuration presents major challenges to designing acceptable closed-loop flight dynamics.

A Robust Design Methodology for Optimal Microscale Secondary Flow Control in Compact Inlet Diffusers

NASA Technical Reports Server (NTRS)

Anderson, Bernhard H.; Keller, Dennis J.

2001-01-01

It is the purpose of this study to develop an economical Robust design methodology for microscale secondary flow control in compact inlet diffusers. To illustrate the potential of economical Robust Design methodology, two different mission strategies were considered for the subject inlet, namely Maximum Performance and Maximum HCF Life Expectancy. The Maximum Performance mission maximized total pressure recovery while the Maximum HCF Life Expectancy mission minimized the mean of the first five Fourier harmonic amplitudes, i.e., 'collectively' reduced all the harmonic 1/2 amplitudes of engine face distortion. Each of the mission strategies was subject to a low engine face distortion constraint, i.e., DC60<0.10, which is a level acceptable for commercial engines. For each of these missions strategies, an 'Optimal Robust' (open loop control) and an 'Optimal Adaptive' (closed loop control) installation was designed over a twenty degree angle-of-incidence range. The Optimal Robust installation used economical Robust Design methodology to arrive at a single design which operated over the entire angle-of-incident range (open loop control). The Optimal Adaptive installation optimized all the design parameters at each angle-of-incidence. Thus, the Optimal Adaptive installation would require a closed loop control system to sense a proper signal for each effector and modify that effector device, whether mechanical or fluidic, for optimal inlet performance. In general, the performance differences between the Optimal Adaptive and Optimal Robust installation designs were found to be marginal. This suggests, however, that Optimal Robust open loop installation designs can be very competitive with Optimal Adaptive close loop designs. Secondary flow control in inlets is inherently robust, provided it is optimally designed. Therefore, the new methodology presented in this paper, combined array 'Lower Order' approach to Robust DOE, offers the aerodynamicist a very viable and economical way of exploring the concept of Robust inlet design, where the mission variables are brought directly into the inlet design process and insensitivity or robustness to the mission variables becomes a design objective.

A Comparison of Multivariable Control Design Techniques for a Turbofan Engine Control

NASA Technical Reports Server (NTRS)

Garg, Sanjay; Watts, Stephen R.

1995-01-01

This paper compares two previously published design procedures for two different multivariable control design techniques for application to a linear engine model of a jet engine. The two multivariable control design techniques compared were the Linear Quadratic Gaussian with Loop Transfer Recovery (LQG/LTR) and the H-Infinity synthesis. The two control design techniques were used with specific previously published design procedures to synthesize controls which would provide equivalent closed loop frequency response for the primary control loops while assuring adequate loop decoupling. The resulting controllers were then reduced in order to minimize the programming and data storage requirements for a typical implementation. The reduced order linear controllers designed by each method were combined with the linear model of an advanced turbofan engine and the system performance was evaluated for the continuous linear system. Included in the performance analysis are the resulting frequency and transient responses as well as actuator usage and rate capability for each design method. The controls were also analyzed for robustness with respect to structured uncertainties in the unmodeled system dynamics. The two controls were then compared for performance capability and hardware implementation issues.

Studies of uranium-sodium suspensions. Part I. Construction and operation of experimental loop

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bett, F L; Hilditch, R J; Mepham, R G

1961-08-01

An experimnental uranium- sodium suspension loop was operated for 4320 hr. The design, construction, commissioning, and operation of the loop to the point where a comnplete stable suspension was obtained is described.

The design of multirate digital control systems

NASA Technical Reports Server (NTRS)

Berg, M. C.

1986-01-01

The successive loop closures synthesis method is the only method for multirate (MR) synthesis in common use. A new method for MR synthesis is introduced which requires a gradient-search solution to a constrained optimization problem. Some advantages of this method are that the control laws for all control loops are synthesized simultaneously, taking full advantage of all cross-coupling effects, and that simple, low-order compensator structures are easily accomodated. The algorithm and associated computer program for solving the constrained optimization problem are described. The successive loop closures , optimal control, and constrained optimization synthesis methods are applied to two example design problems. A series of compensator pairs are synthesized for each example problem. The succesive loop closure, optimal control, and constrained optimization synthesis methods are compared, in the context of the two design problems.

Three-Dimensional Printing of Vitrification Loop Prototypes for Aquatic Species.

PubMed

Tiersch, Nolan J; Childress, William M; Tiersch, Terrence R

2018-05-16

Vitrification is a method of cryopreservation that freezes samples rapidly, while forming an amorphous solid ("glass"), typically in small (μL) volumes. The goal of this project was to create, by three-dimensional (3D) printing, open vitrification devices based on an elliptical loop that could be efficiently used and stored. Vitrification efforts can benefit from the application of 3D printing, and to begin integration of this technology, we addressed four main variables: thermoplastic filament type, loop length, loop height, and method of loading. Our objectives were to: (1) design vitrification loops with varied dimensions; (2) print prototype loops for testing; (3) evaluate loading methods for the devices; and (4) classify vitrification responses to multiple device configurations. The various configurations were designed digitally using 3D CAD (Computer Aided Design) software, and prototype devices were produced with MakerBot ® 3D printers. The thermoplastic filaments used to produce devices were acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA). Vitrification devices were characterized by the film volumes formed with different methods of loading (pipetting or submersion). Frozen films were classified to determine vitrification quality: zero (opaque, or abundant crystalline ice formation); one (translucent, or partial vitrification), or two (transparent, or substantial vitrification, glass). A published vitrification solution was used to conduct experiments. Loading by pipetting formed frozen films more reliably than by submersion, but submersion yielded fewer filling problems and was more rapid. The loop designs that yielded the highest levels of vitrification enabled rapid transfer of heat, and most often were characterized as being longer and consisting of fewer layers (height). 3D printing can assist standardization of vitrification methods and research, yet can also provide the ability to quickly design and fabricate custom devices when needed.

Design and Evaluation of a Water Recirculation Loop Maintenance Device for the Advanced Spacesuit Water Membrane Evaporator

NASA Technical Reports Server (NTRS)

Steele, John W.; Rector, Tony; Bue, Grant C.; Campbell, Colin; Makinen, Janice

2012-01-01

A dual-bed device to maintain the water quality of the Advanced Spacesuit Water Membrane Evaporation (SWME) water recirculation loop has been designed and is undergoing testing. The SWME is a heat rejection device under development at the NASA Johnson Space Center to perform thermal control for advanced spacesuits. One advantage to this technology is the potential for a significantly greater degree of tolerance to contamination when compared to the existing sublimator technology. The driver for the development of a water recirculation maintenance device is to further enhance this advantage through the leveraging of fluid loop management lessons learned from the International Space Station (ISS). A bed design that was developed for a Hamilton Sundstrand military application, and considered for a potential ISS application with the Urine Processor Assembly, provides a low pressure drop means for water maintenance in a recirculation loop. The bed design is coupled with high-capacity ion exchange resins, organic adsorbents, and a cyclic methodology developed for the Extravehicular Mobility Unit Transport Water Loop. The bed design further leverages a sorbent developed for the ISS that introduces a biocide in a microgravity-compatible manner for the Internal Active Thermal Control System. The leveraging of these water maintenance technologies to the SWME recirculation loop is a unique demonstration of applying the valuable lessons learned on the ISS to the next generation of crewed spaceflight Environmental Control and Life Support System hardware.

Design and Evaluation of a Water Recirculation Loop Maintenance Device for the Advanced Spacesuit Water Membrane Evaporator

NASA Technical Reports Server (NTRS)

Steele, John W.; Rector, Tony; Bue, Grant C.; Campbell, Colin; Makinen, Janice

2011-01-01

A dual-bed device to maintain the water quality of the Advanced Spacesuit Water Membrane Evaporation (SWME) water recirculation loop has been designed and is undergoing testing. The SWME is a heat rejection device under development at the NASA Johnson Space Center to perform thermal control for advanced spacesuits. One advantage to this technology is the potential for a significantly greater degree of tolerance to contamination when compared to the existing Sublimator technology. The driver for the development of a water recirculation maintenance device is to further enhance this advantage through the leveraging of fluid loop management lessons-learned from the International Space Station (ISS). A bed design that was developed for a Hamilton Sundstrand military application, and considered for a potential ISS application with the Urine Processor Assembly, provides a low pressure drop means for water maintenance in a recirculation loop. The bed design is coupled with high capacity ion exchange resins, organic adsorbents, and a cyclic methodology developed for the Extravehicular Mobility Unit (EMU) Transport Water loop. The bed design further leverages a sorbent developed for ISS that introduces a biocide in a microgravity-compatible manner for the Internal Active Thermal Control System (IATCS). The leveraging of these water maintenance technologies to the SWME recirculation loop is a clear demonstration of applying the valuable lessons learned on the ISS to the next generation of manned spaceflight Environmental Control and Life Support System (ECLSS) hardware.

NaK Plugging Meter Design for the Feasibility Test Loops

NASA Technical Reports Server (NTRS)

Pearson, J. Boise; Godfroy, Thomas J.; Reid, Robert S.; Polzin, Kurt A.

2008-01-01

The design and predicted performance of a plugging meter for use in the measurement of NaK impurity levels are presented. The plugging meter is incorporated into a Feasibility Test Loop (FTL), which is a small pumped-NaK loop designed to enable the rapid, small-scale evaluation of techniques such as in situ purification methods and to permit the measurement of bulk material transport effects (not mechanisms) under flow conditions that are representative of a fission surface power reactor. The FTL operates at temperatures similar to those found in a reactor, with a maximum hot side temperature of 900 K and a corresponding cold side temperature of 860 K. In the plugging meter a low flow rate bypass loop is cooled until various impurities (primarily oxides) precipitate out of solution. The temperatures at which these impurities precipitate are indicative of the level of impurities in the NaK. The precipitates incrementally plug a small orifice in the bypass loop, which is detected by monitoring changes in the liquid metal flow rate.

Prototype of a gigabit data transmitter in 65 nm CMOS for DEPFET pixel detectors at Belle-II

NASA Astrophysics Data System (ADS)

Kishishita, T.; Krüger, H.; Hemperek, T.; Lemarenko, M.; Koch, M.; Gronewald, M.; Wermes, N.

2013-08-01

This paper describes the recent development of a gigabit data transmitter for the Belle-II pixel detector (PXD). The PXD is an innermost detector currently under development for the upgraded KEK-B factory in Japan. The PXD consists of two layers of DEPFET sensor modules located at 1.8 and 2.2 cm radii. Each module is equipped with three different ASIC types mounted on the detector substrate with a flip-chip technique: (a) SWITCHER for generating steering signals for the DEPFET sensors, (b) DCD for digitizing the signal currents, and (c) DHP for performing data processing and sending the data off the module to the back-end data handling hybrid via ∼ 40 cm Kapton flex and 12-15 m twisted pair (TWP) cables. To meet the requirements of the PXD data transmission, a prototype of the DHP data transmitter has been developed in a 65-nm standard CMOS technology. The transmitter test chip consists of current-mode logic (CML) drivers and a phase-locked loop (PLL) which generates a clock signal for a 1.6 Gbit/s output data stream from an 80 cm reference clock. A programmable pre-emphasis circuit is also implemented in the CML driver to compensate signal losses in the long cable by shaping the transmitted pulse response. The jitter performance was measured as 25 ps (1 σ distribution) by connecting the chip with 38 cm flex and 10 m TWP cables.

Human health monitoring technology

NASA Astrophysics Data System (ADS)

Kim, Byung-Hyun; Yook, Jong-Gwan

2017-05-01

Monitoring vital signs from human body is very important to healthcare and medical diagnosis, because they contain valuable information about arterial occlusions, arrhythmia, atherosclerosis, autonomous nervous system pathologies, stress level, and obstructive sleep apnea. Existing methods, such as electrocardiogram (ECG) sensor and photoplethysmogram (PPG) sensor, requires direct contact to the skin and it can causes skin irritation and the inconvenience of long-term wearing. For reducing the inconvenience in the conventional sensors, microwave and millimeter-wave sensors have been proposed since 1970s using micro-Doppler effect from one's cardiopulmonary activity. The Doppler radar sensor can remotely detect the respiration and heartbeat up to few meters away from the subject, but they have a multiple subject issue and are not suitable for an ambulatory subject. As a compromise, a noncontact proximity vital sign sensor has been recently proposed and developed. The purpose of this paper is to review the noncontact proximity vital sign sensors for detection of respiration, heartbeat rate, and/or wrist pulse. This sensor basically employs near-field perturbation of radio-frequency (RF) planar resonator due to the proximity of the one's chest or radial artery at the wrist. Various sensing systems based on the SAW filter, phase-locked loop (PLL) synthesizer, reflectometer, and interferometer have been proposed. These self-sustained systems can measure the nearfield perturbation and transform it into DC voltage variation. Consequently, they can detect the respiration and heartbeat rate near the chest of subject and pulse from radial artery at the wrist.

Force microscopy experiments with ultrasensitive cantilevers.

PubMed

Rast, S; Gysin, U; Ruff, P; Gerber, Ch; Meyer, E; Lee, D W

2006-04-14

Force microscopy experiments with the pendulum geometry are performed with attonewton sensitivity (Rugar et al 2004 Nature 43 329). Single-crystalline cantilevers with sub-millinewton spring constants were annealed under ultrahigh-vacuum conditions. It is found that annealing with temperatures below 500 °C can improve the quality factor by an order of magnitude. The high force sensitivity of these ultrasoft cantilevers is used to characterize small magnetic and superconductive particles, which are mounted on the end of the cantilever. Their magnetic properties are analysed in magnetic fields as a function of temperature. The transition of a superconducting sample mounted on a cantilever is measured by the detection of frequency shifts. An increase of dissipation is observed below the critical temperature. The magnetic moment of ferromagnetic particles is determined by real time frequency detection with a phase-locked loop (PLL) as a function of the magnetic field. The dissipation between the probing tip and the sample is another important ingredient for ultrasensitive force measurements. It is found that dissipation increases at separations of 30 nm. The origins of this type of dissipation are poorly understood. However, it is predicted theoretically that adsorbates can increase this dissipation channel (Volokitin and Persson 2005 Phys. Rev. Lett. 94 086104). First experiments are performed under ultrahigh vacuum to investigate this type of dissipation. Long-range dissipation is closely related to long-range forces. The distance dependence of the contact potential is found to be an important aspect.

Evaluating Mathematics Achievement of Middle School Students in a Looping Environment

ERIC Educational Resources Information Center

Franz, Dana Pomykal; Thompson, Nicole L.; Fuller, Bob; Hare, R. Dwight; Miller, Nicole C.; Walker, Jacob

2010-01-01

Looping, a school structure where students remain with one group of teachers for two or more school years, is used by middle schools to meet the diverse needs of young adolescents. However, little research exists on how looping effects the academic performance of students. This study was designed to determine if looping influenced middle school…

U.S. EPA, Pesticide Product Label, , 01/20/1984

EPA Pesticide Factsheets

2011-04-14

... "'" ,j: t·· " •• j'- . " . t ~ • !" f nh', -')to;l(r .. , ilP'oqPf"lt'S p, "Pus rT"I,lb,l(c;, r.:,t)''JP11.1 [)y'il'nh'fllf' g·.· .. to.lCll-"'f,U'·' .I"q'· "",I~'" .' t:n'u"pll,1 fyptll ...

DSU Repair Parts Stockouts

DTIC Science & Technology

1976-06-01

37 7. Training of Class IX Suppl- Personnel ----------- 2-40 8. Training of Division PLL Clerks ----------------- 2-42 iv *m1 PAGE 9. Essentiality of...Requisition Followups ---------------------------- 2-78 9. Forecasting Production Leadtimes ----------------- 2-79 10. Repair Parts Essentiality ... essentiality coding are discussed. xi SUMMARY 1. !NTRODUCTION. It has been observed on repeated occasions that major items of equipment are deadlined for

A method for reducing sampling jitter in digital control systems

NASA Technical Reports Server (NTRS)

Anderson, T. O.; HURBD W. J.; Hurd, W. J.

1969-01-01

Digital phase lock loop system is designed by smoothing the proportional control with a low pass filter. This method does not significantly affect the loop dynamics when the smoothing filter bandwidth is wide compared to loop bandwidth.

Multifrequency zero-jitter delay-locked loop

NASA Astrophysics Data System (ADS)

Efendovich, Avner; Afek, Yachin; Sella, Coby; Bikowsky, Zeev

1994-01-01

The approach of an all-digital phase locked loop is used in this delay-locked loop circuit. This design is designated to a system with two processing units, a master CPU and a slave system chip, that share the same bus. It allows maximum utilization of the bus, as the minimal skew between the clocks of the two components significantly reduces idle periods, and also set-up and hold times. Changes in the operating frequency are possible, without falling out of synchronization. Due to the special lead-lag phase detector, the jitter of the clock is zero, when the loop is locked, under any working conditions.

Mitigating Communication Delays in Remotely Connected Hardware-in-the-loop Experiments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cale, James; Johnson, Brian; Dall'Anese, Emiliano

Here, this paper introduces a potential approach for mitigating the effects of communication delays between multiple, closed-loop hardware-in-the-loop experiments which are virtually connected, yet physically separated. The method consists of an analytical method for the compensation of communication delays, along with the supporting computational and communication infrastructure. The control design leverages tools for the design of observers for the compensation of measurement errors in systems with time-varying delays. The proposed methodology is validated through computer simulation and hardware experimentation connecting hardware-in-the-loop experiments conducted between laboratories separated by a distance of over 100 km.

Mitigating Communication Delays in Remotely Connected Hardware-in-the-loop Experiments

DOE PAGES

Cale, James; Johnson, Brian; Dall'Anese, Emiliano; ...

2018-03-30

Here, this paper introduces a potential approach for mitigating the effects of communication delays between multiple, closed-loop hardware-in-the-loop experiments which are virtually connected, yet physically separated. The method consists of an analytical method for the compensation of communication delays, along with the supporting computational and communication infrastructure. The control design leverages tools for the design of observers for the compensation of measurement errors in systems with time-varying delays. The proposed methodology is validated through computer simulation and hardware experimentation connecting hardware-in-the-loop experiments conducted between laboratories separated by a distance of over 100 km.

Implementing Audio Digital Feedback Loop Using the National Instruments RIO System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, G.; Byrd, J. M.

2006-11-20

Development of system for high precision RF distribution and laser synchronization at Berkeley Lab has been ongoing for several years. Successful operation of these systems requires multiple audio bandwidth feedback loops running at relatively high gains. Stable operation of the feedback loops requires careful design of the feedback transfer function. To allow for flexible and compact implementation, we have developed digital feedback loops on the National Instruments Reconfigurable Input/Output (RIO) platform. This platform uses an FPGA and multiple I/Os that can provide eight parallel channels running different filters. We present the design and preliminary experimental results of this system.

Fast Bayesian experimental design: Laplace-based importance sampling for the expected information gain

NASA Astrophysics Data System (ADS)

Beck, Joakim; Dia, Ben Mansour; Espath, Luis F. R.; Long, Quan; Tempone, Raúl

2018-06-01

In calculating expected information gain in optimal Bayesian experimental design, the computation of the inner loop in the classical double-loop Monte Carlo requires a large number of samples and suffers from underflow if the number of samples is small. These drawbacks can be avoided by using an importance sampling approach. We present a computationally efficient method for optimal Bayesian experimental design that introduces importance sampling based on the Laplace method to the inner loop. We derive the optimal values for the method parameters in which the average computational cost is minimized according to the desired error tolerance. We use three numerical examples to demonstrate the computational efficiency of our method compared with the classical double-loop Monte Carlo, and a more recent single-loop Monte Carlo method that uses the Laplace method as an approximation of the return value of the inner loop. The first example is a scalar problem that is linear in the uncertain parameter. The second example is a nonlinear scalar problem. The third example deals with the optimal sensor placement for an electrical impedance tomography experiment to recover the fiber orientation in laminate composites.

Origin and control of instability in SCR/triac three-phase motor controllers

NASA Technical Reports Server (NTRS)

Dearth, J. J.

1982-01-01

The energy savings and reactive power reduction functions initiated by the power factor controller (PFC) are discussed. A three-phase PFC with soft start is examined analytically and experimentally to determine how well it controls the open loop instability and other possible modes of instability. The detailed mechanism of the open loop instability is determined and shown to impose design constraints on the closed loop system. The design is shown to meet those constraints.

Approximations for Quantitative Feedback Theory Designs

NASA Technical Reports Server (NTRS)

Henderson, D. K.; Hess, R. A.

1997-01-01

The computational requirements for obtaining the results summarized in the preceding section were very modest and were easily accomplished using computer-aided control system design software. Of special significance is the ability of the PDT to indicate a loop closure sequence for MIMO QFT designs that employ sequential loop closure. Although discussed as part of a 2 x 2 design, the PDT is obviously applicable to designs with a greater number of inputs and system responses.

Evaluation of an Adaptive Game that Uses EEG Measures Validated during the Design Process as Inputs to a Biocybernetic Loop.

PubMed

Ewing, Kate C; Fairclough, Stephen H; Gilleade, Kiel

2016-01-01

Biocybernetic adaptation is a form of physiological computing whereby real-time data streaming from the brain and body is used by a negative control loop to adapt the user interface. This article describes the development of an adaptive game system that is designed to maximize player engagement by utilizing changes in real-time electroencephalography (EEG) to adjust the level of game demand. The research consists of four main stages: (1) the development of a conceptual framework upon which to model the interaction between person and system; (2) the validation of the psychophysiological inference underpinning the loop; (3) the construction of a working prototype; and (4) an evaluation of the adaptive game. Two studies are reported. The first demonstrates the sensitivity of EEG power in the (frontal) theta and (parietal) alpha bands to changing levels of game demand. These variables were then reformulated within the working biocybernetic control loop designed to maximize player engagement. The second study evaluated the performance of an adaptive game of Tetris with respect to system behavior and user experience. Important issues for the design and evaluation of closed-loop interfaces are discussed.

Evaluation of an Adaptive Game that Uses EEG Measures Validated during the Design Process as Inputs to a Biocybernetic Loop

PubMed Central

Ewing, Kate C.; Fairclough, Stephen H.; Gilleade, Kiel

2016-01-01

Biocybernetic adaptation is a form of physiological computing whereby real-time data streaming from the brain and body is used by a negative control loop to adapt the user interface. This article describes the development of an adaptive game system that is designed to maximize player engagement by utilizing changes in real-time electroencephalography (EEG) to adjust the level of game demand. The research consists of four main stages: (1) the development of a conceptual framework upon which to model the interaction between person and system; (2) the validation of the psychophysiological inference underpinning the loop; (3) the construction of a working prototype; and (4) an evaluation of the adaptive game. Two studies are reported. The first demonstrates the sensitivity of EEG power in the (frontal) theta and (parietal) alpha bands to changing levels of game demand. These variables were then reformulated within the working biocybernetic control loop designed to maximize player engagement. The second study evaluated the performance of an adaptive game of Tetris with respect to system behavior and user experience. Important issues for the design and evaluation of closed-loop interfaces are discussed. PMID:27242486

SNAP-8 power conversion system design review

NASA Technical Reports Server (NTRS)

Lopez, L. P.

1970-01-01

The conceptual design of the SNAP-8 electrical generating system configurations are reviewed including the evolution of the PCS configuration, and the current concepts. The reliabilities of two alternative PCS-G heat rejection loop configurations with two radiator design concepts are also reviewed. A computer program for calculating system pressure loss using multiple-loop flow analysis is included.

Feedback Control Systems Loop Shaping Design with Practical Considerations

NASA Technical Reports Server (NTRS)

Kopsakis, George

2007-01-01

This paper describes loop shaping control design in feedback control systems, primarily from a practical stand point that considers design specifications. Classical feedback control design theory, for linear systems where the plant transfer function is known, has been around for a long time. But it s still a challenge of how to translate the theory into practical and methodical design techniques that simultaneously satisfy a variety of performance requirements such as transient response, stability, and disturbance attenuation while taking into account the capabilities of the plant and its actuation system. This paper briefly addresses some relevant theory, first in layman s terms, so that it becomes easily understood and then it embarks into a practical and systematic design approach incorporating loop shaping design coupled with lead-lag control compensation design. The emphasis is in generating simple but rather powerful design techniques that will allow even designers with a layman s knowledge in controls to develop effective feedback control designs.

Molecular dynamics simulations of electrostatics and hydration distributions around RNA and DNA motifs

NASA Astrophysics Data System (ADS)

Marlowe, Ashley E.; Singh, Abhishek; Semichaevsky, Andrey V.; Yingling, Yaroslava G.

2009-03-01

Nucleic acid nanoparticles can self-assembly through the formation of complementary loop-loop interactions or stem-stem interactions. Presence and concentration of ions can significantly affect the self-assembly process and the stability of the nanostructure. In this presentation we use explicit molecular dynamics simulations to examine the variations in cationic distributions and hydration environment around DNA and RNA helices and loop-loop interactions. Our simulations show that the potassium and sodium ionic distributions are different around RNA and DNA motifs which could be indicative of ion mediated relative stability of loop-loop complexes. Moreover in RNA loop-loop motifs ions are consistently present and exchanged through a distinct electronegative channel. We will also show how we used the specific RNA loop-loop motif to design a RNA hexagonal nanoparticle.

CUA Annual Meeting Abstracts addition.

PubMed

2012-08-01

: Foley catheters are assumed to drain the bladder to completion. We have previously shown that dependent loops along the drainage tubing create air-locks, which obstruct antegrade urine flow and result in un-drained residual bladder urine. We hypothesized that drainage characteristics of Foley catheters remain poorly understood by urologists and general surgeons. We conducted a nationwide survey of general surgery and urology training program faculty and residents, to assess perceptions of Foley catheter drainage. We designed a novel catheter drainage tube/bag that eliminates air-locks. : An anonymous illustrated questionnaire assessing Foley catheter use patterns and perception was sent to general surgery and urology residency programs (N=108) nationwide. A modified catheter drainage tube/bag unit was designed and tested. An ex vivo catheterized bladder model was designed to measure and compare urine drainage rates with the standard drainage system, versus with our novel design. : A total of 307 responses were collected from residents (55%) and faculty (45%); responses were similar among both groups (p<0.05). The majority reported that at their centers Foley catheter drainage tubes are generally positioned with a dependent loop (94.1%), and, that positioning with a dependent loop, versus without (78.1%) promoted optimal drainage. Antegrade drainage does not occur with a traditional drainage system when a >5.5 inch dependent loop in place. With our proposed design, which eliminates dependent loops, the bladder model emptied to completion consistently. : Traditional Foley catheter drainage systems, as commonly used, evacuate the bladder sub- optimally. More reliable and complete bladder drainage may decrease the incidence of catheter related UTI. The novel modified Foley catheter drainage tube/bag design presented here eliminates dependent loops, to optimize antegrade drainage.

A CMOS Humidity Sensor for Passive RFID Sensing Applications

PubMed Central

Deng, Fangming; He, Yigang; Zhang, Chaolong; Feng, Wei

2014-01-01

This paper presents a low-cost low-power CMOS humidity sensor for passive RFID sensing applications. The humidity sensing element is implemented in standard CMOS technology without any further post-processing, which results in low fabrication costs. The interface of this humidity sensor employs a PLL-based architecture transferring sensor signal processing from the voltage domain to the frequency domain. Therefore this architecture allows the use of a fully digital circuit, which can operate on ultra-low supply voltage and thus achieves low-power consumption. The proposed humidity sensor has been fabricated in the TSMC 0.18 μm CMOS process. The measurements show this humidity sensor exhibits excellent linearity and stability within the relative humidity range. The sensor interface circuit consumes only 1.05 μW at 0.5 V supply voltage and reduces it at least by an order of magnitude compared to previous designs. PMID:24841250

A CMOS humidity sensor for passive RFID sensing applications.

PubMed

Deng, Fangming; He, Yigang; Zhang, Chaolong; Feng, Wei

2014-05-16

This paper presents a low-cost low-power CMOS humidity sensor for passive RFID sensing applications. The humidity sensing element is implemented in standard CMOS technology without any further post-processing, which results in low fabrication costs. The interface of this humidity sensor employs a PLL-based architecture transferring sensor signal processing from the voltage domain to the frequency domain. Therefore this architecture allows the use of a fully digital circuit, which can operate on ultra-low supply voltage and thus achieves low-power consumption. The proposed humidity sensor has been fabricated in the TSMC 0.18 μm CMOS process. The measurements show this humidity sensor exhibits excellent linearity and stability within the relative humidity range. The sensor interface circuit consumes only 1.05 µW at 0.5 V supply voltage and reduces it at least by an order of magnitude compared to previous designs.

Integrated Research/Education University Aircraft Design Program Development

DTIC Science & Technology

2017-04-06

iterations and loop shaping compared to MIMO control methods. Despite the drawbacks, loop closure and classical methods are the design methods most commonly...AFRL-AFOSR-VA-TR-2017-0077 Integrated Research/Education University Aircraft Design Program Development Eli Livne UNIVERSITY OF WASHINGTON 4333...SUBTITLE Integrated Research/Education University Aircraft Design Program Development 5a.  CONTRACT NUMBER 5b.  GRANT NUMBER FA9550-14-1-0027 5c.  PROGRAM

Receiver design and performance characteristics

NASA Technical Reports Server (NTRS)

Simon, M. K.; Yuen, J. H.

1982-01-01

The basic design, principles of operation, and characteristics of deep space communications receivers are examined. In particular, the basic fundamentals of phase-locked loop and Costas loop receivers used for synchronization, tracking, and demodulation of phase-coherent signals in residual carrier and suppressed carrier systems are addressed.

Vehicle load-equalization system

NASA Technical Reports Server (NTRS)

Creasy, W. K.

1976-01-01

System uses cables and associated pulleys to form closed-loop suspension system for terrain compensation. Loop causes reactions at each of three wheels in response to loading at remaining wheel. Simplicity of design should be of interest to designers and manufacturers of construction equipment and off-road vehicles.

Diagonal dominance for the multivariable Nyquist array using function minimization

NASA Technical Reports Server (NTRS)

Leininger, G. G.

1977-01-01

A new technique for the design of multivariable control systems using the multivariable Nyquist array method was developed. A conjugate direction function minimization algorithm is utilized to achieve a diagonal dominant condition over the extended frequency range of the control system. The minimization is performed on the ratio of the moduli of the off-diagonal terms to the moduli of the diagonal terms of either the inverse or direct open loop transfer function matrix. Several new feedback design concepts were also developed, including: (1) dominance control parameters for each control loop; (2) compensator normalization to evaluate open loop conditions for alternative design configurations; and (3) an interaction index to determine the degree and type of system interaction when all feedback loops are closed simultaneously. This new design capability was implemented on an IBM 360/75 in a batch mode but can be easily adapted to an interactive computer facility. The method was applied to the Pratt and Whitney F100 turbofan engine.

A 7T Spine Array Based on Electric Dipole Transmitters

PubMed Central

Duan, Qi; Nair, Govind; Gudino, Natalia; de Zwart, Jacco A.; van Gelderen, Peter; Murphy-Boesch, Joe; Reich, Daniel S.; Duyn, Jeff H.; Merkle, Hellmut

2015-01-01

Purpose In this work the feasibility of using an array of electric dipole antennas for RF transmission in spine MRI at high field is explored. Method A 2-channel transmit array based on an electric dipole design was quantitatively optimized for 7T spine imaging and integrated with a receive array combining 8 loop coils. Using B1+ mapping, the transmit efficiency of the dipole array was compared to a design using quadrature loop pairs. The radio-frequency (RF) energy deposition for each array was measured using a home-built dielectric phantom and MR thermometry. The performance of the proposed array was qualitatively demonstrated in human studies. Results The results indicate dramatically improved transmit efficiency for the dipole design as compared to the loop excitation. Up to 76% gain was achieved within the spinal region. Conclusion For imaging of the spine, electric-dipole based transmitters provided an attractive alternative to the traditional loop-based design. Easy integration with existing receive array technology facilitates practical use at high field. PMID:26190585

Design of multivariable feedback control systems via spectral assignment using reduced-order models and reduced-order observers

NASA Technical Reports Server (NTRS)

Mielke, R. R.; Tung, L. J.; Carraway, P. I., III

1984-01-01

The feasibility of using reduced order models and reduced order observers with eigenvalue/eigenvector assignment procedures is investigated. A review of spectral assignment synthesis procedures is presented. Then, a reduced order model which retains essential system characteristics is formulated. A constant state feedback matrix which assigns desired closed loop eigenvalues and approximates specified closed loop eigenvectors is calculated for the reduced order model. It is shown that the eigenvalue and eigenvector assignments made in the reduced order system are retained when the feedback matrix is implemented about the full order system. In addition, those modes and associated eigenvectors which are not included in the reduced order model remain unchanged in the closed loop full order system. The full state feedback design is then implemented by using a reduced order observer. It is shown that the eigenvalue and eigenvector assignments of the closed loop full order system rmain unchanged when a reduced order observer is used. The design procedure is illustrated by an actual design problem.

Designing Hysteresis with Dipolar Chains

NASA Astrophysics Data System (ADS)

Concha, Andrés; Aguayo, David; Mellado, Paula

2018-04-01

Materials that have hysteretic response to an external field are essential in modern information storage and processing technologies. A myriad of magnetization curves of several natural and artificial materials have previously been measured and each has found a particular mechanism that accounts for it. However, a phenomenological model that captures all the hysteresis loops and at the same time provides a simple way to design the magnetic response of a material while remaining minimal is missing. Here, we propose and experimentally demonstrate an elementary method to engineer hysteresis loops in metamaterials built out of dipolar chains. We show that by tuning the interactions of the system and its geometry we can shape the hysteresis loop which allows for the design of the softness of a magnetic material at will. Additionally, this mechanism allows for the control of the number of loops aimed to realize multiple-valued logic technologies. Our findings pave the way for the rational design of hysteretical responses in a variety of physical systems such as dipolar cold atoms, ferroelectrics, or artificial magnetic lattices, among others.

Designing Hysteresis with Dipolar Chains.

PubMed

Concha, Andrés; Aguayo, David; Mellado, Paula

2018-04-13

Materials that have hysteretic response to an external field are essential in modern information storage and processing technologies. A myriad of magnetization curves of several natural and artificial materials have previously been measured and each has found a particular mechanism that accounts for it. However, a phenomenological model that captures all the hysteresis loops and at the same time provides a simple way to design the magnetic response of a material while remaining minimal is missing. Here, we propose and experimentally demonstrate an elementary method to engineer hysteresis loops in metamaterials built out of dipolar chains. We show that by tuning the interactions of the system and its geometry we can shape the hysteresis loop which allows for the design of the softness of a magnetic material at will. Additionally, this mechanism allows for the control of the number of loops aimed to realize multiple-valued logic technologies. Our findings pave the way for the rational design of hysteretical responses in a variety of physical systems such as dipolar cold atoms, ferroelectrics, or artificial magnetic lattices, among others.

Design of multivariable feedback control systems via spectral assignment using reduced-order models and reduced-order observers

NASA Technical Reports Server (NTRS)

Mielke, R. R.; Tung, L. J.; Carraway, P. I., III

1985-01-01

The feasibility of using reduced order models and reduced order observers with eigenvalue/eigenvector assignment procedures is investigated. A review of spectral assignment synthesis procedures is presented. Then, a reduced order model which retains essential system characteristics is formulated. A constant state feedback matrix which assigns desired closed loop eigenvalues and approximates specified closed loop eigenvectors is calculated for the reduced order model. It is shown that the eigenvalue and eigenvector assignments made in the reduced order system are retained when the feedback matrix is implemented about the full order system. In addition, those modes and associated eigenvectors which are not included in the reduced order model remain unchanged in the closed loop full order system. The fulll state feedback design is then implemented by using a reduced order observer. It is shown that the eigenvalue and eigenvector assignments of the closed loop full order system remain unchanged when a reduced order observer is used. The design procedure is illustrated by an actual design problem.

High Impulse Gun Airborne Demonstration. GAU-13/A Weapon, Feed System, Gun Drive and Electronic Controls.

DTIC Science & Technology

1981-05-01

made to provide mounting bosses for the closed loop conveyor chute . Ten small round bosses were welded onto the housing to provide this support...became necessary to depart from previous closed loop feeder designs . The original feed system consisted of a series of conveyor elements in a flexible...The flexible chuting has been replaced with rigid chuting forming a loop around the gun housing. This design affords the maximum stiffness and hence

Turbofan engine control system design using the LQG/LTR methodology

NASA Technical Reports Server (NTRS)

Garg, Sanjay

1989-01-01

Application of the linear-quadratic-Gaussian with loop-transfer-recovery methodology to design of a control system for a simplified turbofan engine model is considered. The importance of properly scaling the plant to achieve the desired target feedback loop is emphasized. The steps involved in the application of the methodology are discussed via an example, and evaluation results are presented for a reduced-order compensator. The effect of scaling the plant on the stability robustness evaluation of the closed-loop system is studied in detail.

Turbofan engine control system design using the LQG/LTR methodology

NASA Technical Reports Server (NTRS)

Garg, Sanjay

1989-01-01

Application of the Linear-Quadratic-Gaussian with Loop-Transfer-Recovery methodology to design of a control system for a simplified turbofan engine model is considered. The importance of properly scaling the plant to achieve the desired Target-Feedback-Loop is emphasized. The steps involved in the application of the methodology are discussed via an example, and evaluation results are presented for a reduced-order compensator. The effect of scaling the plant on the stability robustness evaluation of the closed-loop system is studied in detail.

Printed Multi-Turn Loop Antenna for RF Bio-Telemetry

NASA Technical Reports Server (NTRS)

Simons, Rainee N.; Hall, David G.; Miranda, Felix A.

2004-01-01

In this paper, a novel printed multi-turn loop antenna for contact-less powering and RF telemetry from implantable bio- MEMS sensors at a design frequency of 300 MHz is demonstrated. In addition, computed values of input reactance, radiation resistance, skin effect resistance, and radiation efficiency for the printed multi-turn loop antenna are presented. The computed input reactance is compared with the measured values and shown to be in fair agreement. The computed radiation efficiency at the design frequency is about 24 percent.

Thermal Vacuum Test of GLAS Propylene Loop Heat Pipe Development Model

NASA Technical Reports Server (NTRS)

Baker, Charles; Butler, Dan; Ku, Jentung; Kaya, Tarik; Nikitkin, Michael

2000-01-01

This paper presents viewgraphs on Thermal Vacuum Tests of the GLAS (Geoscience Laser Altimeter System) Propylene Loop Heat Pipe Development Model. The topics include: 1) Flight LHP System (Laser); 2) Test Design and Objectives; 3) DM (Development Model) LHP (Loop Heat Pipe) Test Design; 4) Starter Heater and Coupling Blocks; 5) CC Control Heaters and PRT; 6) Heater Plates (Shown in Reflux Mode); 7) Startup Tests; 8) CC Control Heater Power Tests for CC Temperature Control; and 9) Control Temperature Stability.

A simple second-order digital phase-locked loop.

NASA Technical Reports Server (NTRS)

Tegnelia, C. R.

1972-01-01

A simple second-order digital phase-locked loop has been designed for the Viking Orbiter 1975 command system. Excluding analog-to-digital conversion, implementation of the loop requires only an adder/subtractor, two registers, and a correctable counter with control logic. The loop considers only the polarity of phase error and corrects system clocks according to a filtered sequence of this polarity. The loop is insensitive to input gain variation, and therefore offers the advantage of stable performance over long life. Predictable performance is guaranteed by extreme reliability of acquisition, yet in the steady state the loop produces only a slight degradation with respect to analog loop performance.

Evaluation of Effects and Effectiveness of Various α and β Angulations for Three Different Loop Made of Stainless Steel Arch Wires - A FEM Study.

PubMed

Kamisetty, Supradeep Kumar; N, Raghuveer; N, Rajavikram; N, Chakrapani; Dwaragesh; Praven

2014-07-01

Evaluations on retraction loop designs have been limited to describe the force systems applied to the buccal surfaces of the tooth that can be in different planes resulting undesirable effects, needing corrective action in future. By initially understanding these effects, modifications to the loop design can essentially counteract the undesired affects. To deter-mine Moments & M/F ratios produced by different gabling in the three retraction loops (Tear drop loop, T-loop, Open vertical loop) and movement of the anterior teeth and posterior teeth) of the maxillary arch in an extraction model, on activation of three retraction loops by1 mm. A PC with Quad core processor, 8GB RAM, 1TB storage space and Graphic Accelerator was used. Computer Software: ANSYS Version11, PRO/ENGINEER was used in the study. The first step is modeling, done by using Pro/Engineer software and for creating a model the CT scan data is required. The maxilla with teeth of a patient is scanned at various sections at regular intervals of 0.5 mm. These scanned images are then imported into Pro/E software to various offset planes. Once imported, the software can do an automatic meshing and establishes contact automatically. When angulations increases intrusive or extrusive movements and movements in horizontal direction of crown tip and root tip increases. All values of T-loop are more than Teardrop loop and less than Open vertical loop. FEM study concludes that Teardrop loop with 10-20(α-β) combination is preferred for Group A anchorage.

A bi-directional two-phase/two-phase heat exchanger

NASA Technical Reports Server (NTRS)

Ku, Jentung; Ottenstein, Laura

1993-01-01

This paper describes the design and test of a heat exchanger that transfers heat from one two-phase thermal loop to another with very small drops in temperature and pressure. The heat exchanger condenses the vapor in one loop while evaporating the liquid in the other without mixing of the condensing and evaporating fluids. The heat exchanger is bidirectional in that it can transfer heat in reverse, condensing on the normally evaporating side and vice versa. It is fully compatible with capillary pumped loops and mechanically pumped loops. Test results verified that performance of the heat exchanger met the design requirements. It demonstrated a heat transfer rate of 6800 watts in the normal mode of operation and 1000 watts in the reverse mode with temperature drops of less than 5 C between two thermal loops.

Protein loop modeling using a new hybrid energy function and its application to modeling in inaccurate structural environments.

PubMed

Park, Hahnbeom; Lee, Gyu Rie; Heo, Lim; Seok, Chaok

2014-01-01

Protein loop modeling is a tool for predicting protein local structures of particular interest, providing opportunities for applications involving protein structure prediction and de novo protein design. Until recently, the majority of loop modeling methods have been developed and tested by reconstructing loops in frameworks of experimentally resolved structures. In many practical applications, however, the protein loops to be modeled are located in inaccurate structural environments. These include loops in model structures, low-resolution experimental structures, or experimental structures of different functional forms. Accordingly, discrepancies in the accuracy of the structural environment assumed in development of the method and that in practical applications present additional challenges to modern loop modeling methods. This study demonstrates a new strategy for employing a hybrid energy function combining physics-based and knowledge-based components to help tackle this challenge. The hybrid energy function is designed to combine the strengths of each energy component, simultaneously maintaining accurate loop structure prediction in a high-resolution framework structure and tolerating minor environmental errors in low-resolution structures. A loop modeling method based on global optimization of this new energy function is tested on loop targets situated in different levels of environmental errors, ranging from experimental structures to structures perturbed in backbone as well as side chains and template-based model structures. The new method performs comparably to force field-based approaches in loop reconstruction in crystal structures and better in loop prediction in inaccurate framework structures. This result suggests that higher-accuracy predictions would be possible for a broader range of applications. The web server for this method is available at http://galaxy.seoklab.org/loop with the PS2 option for the scoring function.

Creating stable stem regions for loop elongation in Fcabs — Insights from combining yeast surface display, in silico loop reconstruction and molecular dynamics simulations

PubMed Central

Hasenhindl, Christoph; Lai, Balder; Delgado, Javier; Traxlmayr, Michael W.; Stadlmayr, Gerhard; Rüker, Florian; Serrano, Luis; Oostenbrink, Chris; Obinger, Christian

2014-01-01

Fcabs (Fc antigen binding) are crystallizable fragments of IgG where the C-terminal structural loops of the CH3 domain are engineered for antigen binding. For the design of libraries it is beneficial to know positions that will permit loop elongation to increase the potential interaction surface with antigen. However, the insertion of additional loop residues might impair the immunoglobulin fold. In the present work we have probed whether stabilizing mutations flanking the randomized and elongated loop region improve the quality of Fcab libraries. In detail, 13 libraries were constructed having the C-terminal part of the EF loop randomized and carrying additional residues (1, 2, 3, 5 or 10, respectively) in the absence and presence of two flanking mutations. The latter have been demonstrated to increase the thermal stability of the CH3 domain of the respective solubly expressed proteins. Assessment of the stability of the libraries expressed on the surface of yeast cells by flow cytometry demonstrated that loop elongation was considerably better tolerated in the stabilized libraries. By using in silico loop reconstruction and mimicking randomization together with MD simulations the underlying molecular dynamics were investigated. In the presence of stabilizing stem residues the backbone flexibility of the engineered EF loop as well as the fluctuation between its accessible conformations were decreased. In addition the CD loop (but not the AB loop) and most of the framework regions were rigidified. The obtained data are discussed with respect to the design of Fcabs and available data on the relation between flexibility and affinity of CDR loops in Ig-like molecules. PMID:24792385

Creating stable stem regions for loop elongation in Fcabs - insights from combining yeast surface display, in silico loop reconstruction and molecular dynamics simulations.

PubMed

Hasenhindl, Christoph; Lai, Balder; Delgado, Javier; Traxlmayr, Michael W; Stadlmayr, Gerhard; Rüker, Florian; Serrano, Luis; Oostenbrink, Chris; Obinger, Christian

2014-09-01

Fcabs (Fc antigen binding) are crystallizable fragments of IgG where the C-terminal structural loops of the CH3 domain are engineered for antigen binding. For the design of libraries it is beneficial to know positions that will permit loop elongation to increase the potential interaction surface with antigen. However, the insertion of additional loop residues might impair the immunoglobulin fold. In the present work we have probed whether stabilizing mutations flanking the randomized and elongated loop region improve the quality of Fcab libraries. In detail, 13 libraries were constructed having the C-terminal part of the EF loop randomized and carrying additional residues (1, 2, 3, 5 or 10, respectively) in the absence and presence of two flanking mutations. The latter have been demonstrated to increase the thermal stability of the CH3 domain of the respective solubly expressed proteins. Assessment of the stability of the libraries expressed on the surface of yeast cells by flow cytometry demonstrated that loop elongation was considerably better tolerated in the stabilized libraries. By using in silico loop reconstruction and mimicking randomization together with MD simulations the underlying molecular dynamics were investigated. In the presence of stabilizing stem residues the backbone flexibility of the engineered EF loop as well as the fluctuation between its accessible conformations were decreased. In addition the CD loop (but not the AB loop) and most of the framework regions were rigidified. The obtained data are discussed with respect to the design of Fcabs and available data on the relation between flexibility and affinity of CDR loops in Ig-like molecules. Copyright © 2014. Published by Elsevier B.V.

Man-in-the-control-loop simulation of manipulators

NASA Technical Reports Server (NTRS)

Chang, J. L.; Lin, Tsung-Chieh; Yae, K. Harold

1989-01-01

A method to achieve man-in-the-control-loop simulation is presented. Emerging real-time dynamics simulation suggests a potential for creating an interactive design workstation with a human operator in the control loop. The recursive formulation for multibody dynamics simulation is studied to determine requirements for man-in-the-control-loop simulation. High speed computer graphics techniques provides realistic visual cues for the simulator. Backhoe and robot arm simulations are implemented to demonstrate the capability of man-in-the-control-loop simulation.

The insertion of human dynamics models in the flight control loops of V/STOL research aircraft. Appendix 2: The optimal control model of a pilot in V/STOL aircraft control loops

NASA Technical Reports Server (NTRS)

Zipf, Mark E.

1989-01-01

An overview is presented of research work focussed on the design and insertion of classical models of human pilot dynamics within the flight control loops of V/STOL aircraft. The pilots were designed and configured for use in integrated control system research and design. The models of human behavior that were considered are: McRuer-Krendel (a single variable transfer function model); and Optimal Control Model (a multi-variable approach based on optimal control and stochastic estimation theory). These models attempt to predict human control response characteristics when confronted with compensatory tracking and state regulation tasks. An overview, mathematical description, and discussion of predictive limitations of the pilot models is presented. Design strategies and closed loop insertion configurations are introduced and considered for various flight control scenarios. Models of aircraft dynamics (both transfer function and state space based) are developed and discussed for their use in pilot design and application. Pilot design and insertion are illustrated for various flight control objectives. Results of pilot insertion within the control loops of two V/STOL research aricraft (Sikorski Black Hawk UH-60A, McDonnell Douglas Harrier II AV-8B) are presented and compared against actual pilot flight data. Conclusions are reached on the ability of the pilot models to adequately predict human behavior when confronted with similar control objectives.

Systematic study of alginate-based microcapsules by micropipette aspiration and confocal fluorescence microscopy.

PubMed

Kleinberger, Rachelle M; Burke, Nicholas A D; Dalnoki-Veress, Kari; Stöver, Harald D H

2013-10-01

Micropipette aspiration and confocal fluorescence microscopy were used to study the structure and mechanical properties of calcium alginate hydrogel beads (A beads), as well as A beads that were additionally coated with poly-L-lysine (P) and sodium alginate (A) to form, respectively, AP and APA hydrogels. A beads were found to continue curing for up to 500 h during storage in saline, due to residual calcium chloride carried over from the gelling bath. In subsequent saline washes, micropipette aspiration proved to be a sensitive indicator of gel weakening and calcium loss. Aspiration tests were used to compare capsule stiffness before and after citrate extraction of calcium. They showed that the initial gel strength is largely due to the calcium alginate gel cores, while the long term strength is solely due to the poly-L-lysine-alginate polyelectrolyte complex (PEC) shells. Confocal fluorescence microscopy showed that calcium chloride exposure after PLL deposition led to PLL redistribution into the hydrogel bead, resulting in thicker but more diffuse and weaker PEC shells. Adding a final alginate coating to form APA capsules did not significantly change the PEC membrane thickness and stiffness, but did speed the loss of calcium from the bead core. © 2013.

Hydrogel-laden paper scaffold system for origami-based tissue engineering

PubMed Central

Kim, Su-Hwan; Lee, Hak Rae; Yu, Seung Jung; Han, Min-Eui; Lee, Doh Young; Kim, Soo Yeon; Ahn, Hee-Jin; Han, Mi-Jung; Lee, Tae-Ik; Kim, Taek-Soo; Kwon, Seong Keun; Im, Sung Gap; Hwang, Nathaniel S.

2015-01-01

In this study, we present a method for assembling biofunctionalized paper into a multiform structured scaffold system for reliable tissue regeneration using an origami-based approach. The surface of a paper was conformally modified with a poly(styrene-co-maleic anhydride) layer via initiated chemical vapor deposition followed by the immobilization of poly-l-lysine (PLL) and deposition of Ca2+. This procedure ensures the formation of alginate hydrogel on the paper due to Ca2+ diffusion. Furthermore, strong adhesion of the alginate hydrogel on the paper onto the paper substrate was achieved due to an electrostatic interaction between the alginate and PLL. The developed scaffold system was versatile and allowed area-selective cell seeding. Also, the hydrogel-laden paper could be folded freely into 3D tissue-like structures using a simple origami-based method. The cylindrically constructed paper scaffold system with chondrocytes was applied into a three-ring defect trachea in rabbits. The transplanted engineered tissues replaced the native trachea without stenosis after 4 wks. As for the custom-built scaffold system, the hydrogel-laden paper system will provide a robust and facile method for the formation of tissues mimicking native tissue constructs. PMID:26621717

Hydrogel-laden paper scaffold system for origami-based tissue engineering.

PubMed

Kim, Su-Hwan; Lee, Hak Rae; Yu, Seung Jung; Han, Min-Eui; Lee, Doh Young; Kim, Soo Yeon; Ahn, Hee-Jin; Han, Mi-Jung; Lee, Tae-Ik; Kim, Taek-Soo; Kwon, Seong Keun; Im, Sung Gap; Hwang, Nathaniel S

2015-12-15

In this study, we present a method for assembling biofunctionalized paper into a multiform structured scaffold system for reliable tissue regeneration using an origami-based approach. The surface of a paper was conformally modified with a poly(styrene-co-maleic anhydride) layer via initiated chemical vapor deposition followed by the immobilization of poly-l-lysine (PLL) and deposition of Ca(2+). This procedure ensures the formation of alginate hydrogel on the paper due to Ca(2+) diffusion. Furthermore, strong adhesion of the alginate hydrogel on the paper onto the paper substrate was achieved due to an electrostatic interaction between the alginate and PLL. The developed scaffold system was versatile and allowed area-selective cell seeding. Also, the hydrogel-laden paper could be folded freely into 3D tissue-like structures using a simple origami-based method. The cylindrically constructed paper scaffold system with chondrocytes was applied into a three-ring defect trachea in rabbits. The transplanted engineered tissues replaced the native trachea without stenosis after 4 wks. As for the custom-built scaffold system, the hydrogel-laden paper system will provide a robust and facile method for the formation of tissues mimicking native tissue constructs.

Multi-Purpose Thermal Hydraulic Loop: Advanced Reactor Technology Integral System Test (ARTIST) Facility for Support of Advanced Reactor Technologies

DOE Office of Scientific and Technical Information (OSTI.GOV)

James E. O'Brien; Piyush Sabharwall; SuJong Yoon

2001-11-01

Effective and robust high temperature heat transfer systems are fundamental to the successful deployment of advanced reactors for both power generation and non-electric applications. Plant designs often include an intermediate heat transfer loop (IHTL) with heat exchangers at either end to deliver thermal energy to the application while providing isolation of the primary reactor system. In order to address technical feasibility concerns and challenges a new high-temperature multi-fluid, multi-loop test facility “Advanced Reactor Technology Integral System Test facility” (ARTIST) is under development at the Idaho National Laboratory. The facility will include three flow loops: high-temperature helium, molten salt, and steam/water.more » Details of some of the design aspects and challenges of this facility, which is currently in the conceptual design phase, are discussed« less

Analytical design and evaluation of an active control system for helicopter vibration reduction and gust response alleviation

NASA Technical Reports Server (NTRS)

Taylor, R. B.; Zwicke, P. E.; Gold, P.; Miao, W.

1980-01-01

An analytical study was conducted to define the basic configuration of an active control system for helicopter vibration and gust response alleviation. The study culminated in a control system design which has two separate systems: narrow band loop for vibration reduction and wider band loop for gust response alleviation. The narrow band vibration loop utilizes the standard swashplate control configuration to input controller for the vibration loop is based on adaptive optimal control theory and is designed to adapt to any flight condition including maneuvers and transients. The prime characteristics of the vibration control system is its real time capability. The gust alleviation control system studied consists of optimal sampled data feedback gains together with an optimal one-step-ahead prediction. The prediction permits the estimation of the gust disturbance which can then be used to minimize the gust effects on the helicopter.

Decoupling PI Controller Design for a Normal Conducting RF Cavity Using a Recursive LEVENBERG-MARQUARDT Algorithm

NASA Astrophysics Data System (ADS)

Kwon, Sung-il; Lynch, M.; Prokop, M.

2005-02-01

This paper addresses the system identification and the decoupling PI controller design for a normal conducting RF cavity. Based on the open-loop measurement data of an SNS DTL cavity, the open-loop system's bandwidths and loop time delays are estimated by using batched least square. With the identified system, a PI controller is designed in such a way that it suppresses the time varying klystron droop and decouples the In-phase and Quadrature of the cavity field. The Levenberg-Marquardt algorithm is applied for nonlinear least squares to obtain the optimal PI controller parameters. The tuned PI controller gains are downloaded to the low-level RF system by using channel access. The experiment of the closed-loop system is performed and the performance is investigated. The proposed tuning method is running automatically in real time interface between a host computer with controller hardware through ActiveX Channel Access.

Relative position control design of receiver UAV in flying-boom aerial refueling phase.

PubMed

An, Shuai; Yuan, Suozhong

2018-02-01

This paper proposes the design of the relative position-keeping control of the receiver unmanned aerial vehicle (UAV) with the time-varying mass in the refueling phase utilizing an inner-outer loop structure. Firstly, the model of the receiver in the refueling phase is established. And then tank model is set up to analyze the influence of fuel transfer on the receiver. Subsequently, double power reaching law based sliding mode controller is designed to control receiver translational motion relative to tanker aircraft in the outer loop while active disturbance rejection control technique is applied to the inner loop to stabilize the receiver. In addition, the closed-loop stabilities of the subsystems are established, respectively. Finally, an aerial refueling model under various refueling strategies is utilized. Simulations and comparative analysis demonstrate the effectiveness and robustness of the proposed controllers. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

Robust fast controller design via nonlinear fractional differential equations.

PubMed

Zhou, Xi; Wei, Yiheng; Liang, Shu; Wang, Yong

2017-07-01

A new method for linear system controller design is proposed whereby the closed-loop system achieves both robustness and fast response. The robustness performance considered here means the damping ratio of closed-loop system can keep its desired value under system parameter perturbation, while the fast response, represented by rise time of system output, can be improved by tuning the controller parameter. We exploit techniques from both the nonlinear systems control and the fractional order systems control to derive a novel nonlinear fractional order controller. For theoretical analysis of the closed-loop system performance, two comparison theorems are developed for a class of fractional differential equations. Moreover, the rise time of the closed-loop system can be estimated, which facilitates our controller design to satisfy the fast response performance and maintain the robustness. Finally, numerical examples are given to illustrate the effectiveness of our methods. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

Reliable numerical computation in an optimal output-feedback design

NASA Technical Reports Server (NTRS)

Vansteenwyk, Brett; Ly, Uy-Loi

1991-01-01

A reliable algorithm is presented for the evaluation of a quadratic performance index and its gradients with respect to the controller design parameters. The algorithm is a part of a design algorithm for optimal linear dynamic output-feedback controller that minimizes a finite-time quadratic performance index. The numerical scheme is particularly robust when it is applied to the control-law synthesis for systems with densely packed modes and where there is a high likelihood of encountering degeneracies in the closed-loop eigensystem. This approach through the use of an accurate Pade series approximation does not require the closed-loop system matrix to be diagonalizable. The algorithm was included in a control design package for optimal robust low-order controllers. Usefulness of the proposed numerical algorithm was demonstrated using numerous practical design cases where degeneracies occur frequently in the closed-loop system under an arbitrary controller design initialization and during the numerical search.

Stability analysis and compensation of a boost regulator with two-loop control

NASA Technical Reports Server (NTRS)

Wester, G. W.

1974-01-01

A useful stability measure has been demonstrated by Wester (1973) for switching regulators with a single feedback loop by applying the Nyquist criterion to the approximate loop gain determined by a time-averaging technique. This approach is extended and applied to the characterization, stability analysis, and compensation design of a switching regulator with two-loop control. The role and relative significance of each control loop is clarified on the basis of a description of circuit operation, and the major and minor loops are identified. In view of the inapplicability of linear feedback theory, describing functions of the feedback loops and power stage are derived, using small-signal analysis. Several phenomena revealed from an analysis of the major loop gain are discussed.

Performance of a Water Recirculation Loop Maintenance Device and Process for the Advanced Spacesuit Water Membrane Evaporator

NASA Technical Reports Server (NTRS)

Steele, John W.; Rector, Tony; Bue, Grant C.; Campbell, Colin; Makinen, Janice

2013-01-01

A dual-bed device to maintain the water quality of the Advanced Spacesuit Water Membrane Evaporation (SWME) water recirculation loop has been designed and is undergoing testing. The SWME is a heat rejection device under development at the NASA Johnson Space Center to perform thermal control for advanced spacesuits. One advantage to this technology is the potential for a significantly greater degree of tolerance to contamination when compared to the existing Sublimator technology. The driver for the development of a water recirculation maintenance device is to further enhance this advantage through the leveraging of fluid loop management lessons-learned from the International Space Station (ISS). A bed design that was developed for a Hamilton Sundstrand military application, and considered for a potential ISS application with the Urine Processor Assembly, provides a low pressure drop means for water maintenance in a recirculation loop. The bed design is coupled with high capacity ion exchange resins, organic adsorbents, and a cyclic methodology developed for the Extravehicular Mobility Unit (EMU) Transport Water loop. The bed design further leverages a sorbent developed for ISS that introduces a biocide in a microgravity-compatible manner for the Internal Active Thermal Control System (IATCS). The leveraging of these water maintenance technologies to the SWME recirculation loop is a unique demonstration of applying the valuable lessons learned on the ISS to the next generation of manned spaceflight Environmental Control and Life Support System (ECLSS) hardware.

Livermore Compiler Analysis Loop Suite

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hornung, R. D.

2013-03-01

LCALS is designed to evaluate compiler optimizations and performance of a variety of loop kernels and loop traversal software constructs. Some of the loop kernels are pulled directly from "Livermore Loops Coded in C", developed at LLNL (see item 11 below for details of earlier code versions). The older suites were used to evaluate floating-point performances of hardware platforms prior to porting larger application codes. The LCALS suite is geared toward assissing C++ compiler optimizations and platform performance related to SIMD vectorization, OpenMP threading, and advanced C++ language features. LCALS contains 20 of 24 loop kernels from the older Livermoremore » Loop suites, plus various others representative of loops found in current production appkication codes at LLNL. The latter loops emphasize more diverse loop constructs and data access patterns than the others, such as multi-dimensional difference stencils. The loops are included in a configurable framework, which allows control of compilation, loop sampling for execution timing, which loops are run and their lengths. It generates timing statistics for analysis and comparing variants of individual loops. Also, it is easy to add loops to the suite as desired.« less

Linking Outcomes to Organizational Planning.

ERIC Educational Resources Information Center

Ligon, Glynn; Jackson, Elaine

Linking Outcomes to Organizational Planning (LOOP) was initiated during the 1984-85 school year in the Austin (Texas) Independent School District. LOOP was designed to ensure that evaluation, research, and informal findings became part of the instructional planning loop; to provide information to the Superintendent on progress toward priorities…

Time delay compensation for closed-loop insulin delivery systems: a simulation study.

PubMed

Reboldi, G P; Home, P D; Calabrese, G; Fabietti, P G; Brunetti, P; Massi Benedetti, M

1991-06-01

Closed loop insulin therapy certainly represents the best possible approach to insulin replacement. However, present limitations preclude wider application of the so-called artificial pancreas. Therefore, a thorough understanding of these limitations is needed to design better systems for future long-term use. The present simulation study was design: to obtain better information on the impact of the measurement delay of currently available closed-loop devices both during closed-loop insulin delivery and blood glucose clamp studies, and to design and test a time delay compensator based on the method originally described by O.J. Smith. Simulations were performed on a Compaq Deskpro 486/25 personal computer under MS-DOS operating system using Simnon rel. 3.00 software. There was a direct relationship between measurement delay and amount of insulin delivered, i.e., the longer the delay the higher the insulin dose needed to control a rise in blood glucose; the closed-loop response in presence of a time delay was qualitatively impaired both during insulin delivery and blood glucose clamp studies; time delay compensation was effective in reducing the insulin dose and improving controller stability during the early phase of clamp studies. However, the robustness of a Smith's predictor-based controller should be carefully evaluated before implementation in closed-loop systems can be considered.

Predicting the effects of unmodeled dynamics on an aircraft flight control system design using eigenspace assignment

NASA Technical Reports Server (NTRS)

Johnson, Eric N.; Davidson, John B.; Murphy, Patrick C.

1994-01-01

When using eigenspace assignment to design an aircraft flight control system, one must first develop a model of the plant. Certain questions arise when creating this model as to which dynamics of the plant need to be included in the model and which dynamics can be left out or approximated. The answers to these questions are important because a poor choice can lead to closed-loop dynamics that are unpredicted by the design model. To alleviate this problem, a method has been developed for predicting the effect of not including certain dynamics in the design model on the final closed-loop eigenspace. This development provides insight as to which characteristics of unmodeled dynamics will ultimately affect the closed-loop rigid-body dynamics. What results from this insight is a guide for eigenstructure control law designers to aid them in determining which dynamics need or do not need to be included and a new way to include these dynamics in the flight control system design model to achieve a required accuracy in the closed-loop rigid-body dynamics. The method is illustrated for a lateral-directional flight control system design using eigenspace assignment for the NASA High Alpha Research Vehicle (HARV).

Stability Assessment and Tuning of an Adaptively Augmented Classical Controller for Launch Vehicle Flight Control

NASA Technical Reports Server (NTRS)

VanZwieten, Tannen; Zhu, J. Jim; Adami, Tony; Berry, Kyle; Grammar, Alex; Orr, Jeb S.; Best, Eric A.

2014-01-01

Recently, a robust and practical adaptive control scheme for launch vehicles [ [1] has been introduced. It augments a classical controller with a real-time loop-gain adaptation, and it is therefore called Adaptive Augmentation Control (AAC). The loop-gain will be increased from the nominal design when the tracking error between the (filtered) output and the (filtered) command trajectory is large; whereas it will be decreased when excitation of flex or sloshing modes are detected. There is a need to determine the range and rate of the loop-gain adaptation in order to retain (exponential) stability, which is critical in vehicle operation, and to develop some theoretically based heuristic tuning methods for the adaptive law gain parameters. The classical launch vehicle flight controller design technics are based on gain-scheduling, whereby the launch vehicle dynamics model is linearized at selected operating points along the nominal tracking command trajectory, and Linear Time-Invariant (LTI) controller design techniques are employed to ensure asymptotic stability of the tracking error dynamics, typically by meeting some prescribed Gain Margin (GM) and Phase Margin (PM) specifications. The controller gains at the design points are then scheduled, tuned and sometimes interpolated to achieve good performance and stability robustness under external disturbances (e.g. winds) and structural perturbations (e.g. vehicle modeling errors). While the GM does give a bound for loop-gain variation without losing stability, it is for constant dispersions of the loop-gain because the GM is based on frequency-domain analysis, which is applicable only for LTI systems. The real-time adaptive loop-gain variation of the AAC effectively renders the closed-loop system a time-varying system, for which it is well-known that the LTI system stability criterion is neither necessary nor sufficient when applying to a Linear Time-Varying (LTV) system in a frozen-time fashion. Therefore, a generalized stability metric for time-varying loop=gain perturbations is needed for the AAC.

TREAT Neutronics Analysis of Water-Loop Concept Accommodating LWR 9-rod Bundle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hill, Connie M.; Woolstenhulme, Nicolas E.; Parry, James R.

Abstract. Simulation of a variety of transient conditions has been successfully achieved in the Transient Reactor Test (TREAT) facility during operation between 1959 and 1994 to support characterization and safety analysis of nuclear fuels and materials. A majority of previously conducted tests were focused on supporting sodium-cooled fast reactor (SFR) designs. Experiments evolved in complexity. Simulation of thermal-hydraulic conditions expected to be encountered by fuels and materials in a reactor environment was realized in the development of TREAT sodium loop experiment vehicles. These loops accommodated up to 7-pin fuel bundles and served to simulate more closely the reactor environment whilemore » safely delivering large quantities of energy into the test specimen. Some of the immediate TREAT restart operations will be focused on testing light water reactor (LWR) accident tolerant fuels (ATF). Similar to the sodium loop objectives, a water loop concept, developed and analyzed in the 1990’s, aimed at achieving thermal-hydraulic conditions encountered in commercial power reactors. The historic water loop concept has been analyzed in the context of a reactivity insertion accident (RIA) simulation for high burnup LWR 2-pin and 3-pin fuel bundles. Findings showed sufficient energy could be deposited into the specimens for evaluation. Similar results of experimental feasibility for the water loop concept (past and present) have recently been obtained using MCNP6.1 with ENDF/B-VII.1 nuclear data libraries. The old water loop concept required only two central TREAT core grid spaces. Preparation for future experiments has resulted in a modified water loop conceptual design designated the TREAT water environment recirculating loop (TWERL). The current TWERL design requires nine TREAT core grid spaces in order to place the water recirculating pump under the TREAT core. Due to the effectiveness of water moderation, neutronics analysis shows that removal of seven additional TREAT fuel elements to facilitate the experiment will not inhibit the ability to successfully simulate a RIA for the 2-pin or 3-pin bundle. This new water loop design leaves room for accommodating a larger fuel pin bundle than previously analyzed. The 7-pin fuel bundle in a hexagonal array with similar spacing of fuel pins in a SFR fuel assembly was considered the minimum needed for one central fuel pin to encounter the most correct thermal conditions. The 9-rod fuel bundle in a square array similar in spacing to pins in a LWR fuel assembly would be considered the LWR equivalent. MCNP analysis conducted on a preliminary LWR 9-rod bundle design shows that sufficient energy deposition into the central pin can be achieved well within range to investigate fuel and cladding performance in a simulated RIA. This is achieved by surrounding the flow channel with an additional annulus of water. Findings also show that a highly significant increase in TREAT to specimen power coupling factor (PCF) within the central pin can be achieved by surrounding the experiment with one to two rings of TREAT upgrade fuel assemblies. The experiment design holds promise for the performance evaluation of PWR fuel at extremely high burnup under similar reactor environment conditions.« less

Demonstration of Standard HVAC Single-Loop Digital Control Systems

DTIC Science & Technology

1993-01-01

AD-A265 372 T N FEAP-TR-FE-93/05 REPORT January 1993 FACILITIES ENGINEERING APPLICATIONS PROGRAM Demonstration of Standard HVAC Single-Loop Digital...AND DATES COVERED January 1993 Final 4. TITLE AND SUBTITLE [5. FUNDING NUMBERS Demonstration of Standard HVAC Single-Loop Digital Control Systems FEAP...conditioning ( HVAC ) control systems provide guidance on designing and specifying standard HVAC control systems that use single-loop digital controllers

A spiral, bi-planar gradient coil design for open magnetic resonance imaging.

PubMed

Zhang, Peng; Shi, Yikai; Wang, Wendong; Wang, Yaohui

2018-01-01

To design planar gradient coil for MRI applications without discretization of continuous current density and loop-loop connection errors. In the new design method, the coil current is represented using a spiral curve function described by just a few control parameters. Using a proper parametric equation set, an ensemble of spiral contours is reshaped to satisfy the coil design requirements, such as gradient linearity, inductance and shielding. In the given case study, by using the spiral coil design, the magnetic field errors in the imaging area were reduced from 5.19% (non-spiral design) to 4.47% (spiral design) for the transverse gradient coils, and for the longitudinal gradient coil design, the magnetic field errors were reduced to 5.02% (spiral design). The numerical evaluation shows that when compared with conventional wire loop, the inductance and resistance of spiral coil was reduced by 11.55% and 8.12% for x gradient coil, respectively. A novel spiral gradient coil design for biplanar MRI systems, the new design offers better magnetic field gradients, smooth contours than the conventional connected counterpart, which improves manufacturability.

Multi-GHz Synchronous Waveform Acquisition With Real-Time Pattern-Matching Trigger Generation

NASA Astrophysics Data System (ADS)

Kleinfelder, Stuart A.; Chiang, Shiuh-hua Wood; Huang, Wei

2013-10-01

A transient waveform capture and digitization circuit with continuous synchronous 2-GHz sampling capability and real-time programmable windowed trigger generation has been fabricated and tested. Designed in 0.25 μm CMOS, the digitizer contains a circular array of 128 sample and hold circuits for continuous sample acquisition, and attains 2-GHz sample speeds with over 800-MHz analog bandwidth. Sample clock generation is synchronous, combining a phase-locked loop for high-speed clock generation and a high-speed fully-differential shift register for distributing clocks to all 128 sample circuits. Using two comparators per sample, the sampled voltage levels are compared against two reference levels, a high threshold and a low threshold, that are set via per-comparator digital to analog converters (DACs). The 256 per-comparator 5-bit DACs compensate for comparator offsets and allow for fine reference level adjustment. The comparator results are matched in 8-sample-wide windows against up to 72 programmable patterns in real time using an on-chip programmable logic array. Each 8-sample trigger window is equivalent to 4 ns of acquisition, overlapped sample by sample in a circular fashion through the entire 128-sample array. The 72 pattern-matching trigger criteria can be programmed to be any combination of High-above the high threshold, Low-below the low threshold, Middle-between the two thresholds, or “Don't Care”-any state is accepted. A trigger pattern of “HLHLHLHL,” for example, watches for a waveform that is oscillating at about 1 GHz given the 2-GHz sample rate. A trigger is flagged in under 20 ns if there is a match, after which sampling is stopped, and on-chip digitization can proceed via 128 parallel 10-bit converters, or off-chip conversion can proceed via an analog readout. The chip exceeds 11 bits of dynamic range, nets over 800-MHz -3-dB bandwidth in a realistic system, and jitter in the PLL-based sampling clock has been measured to be about 1 part per million, RMS.

Hippocampal closed-loop modeling and implications for seizure stimulation design

NASA Astrophysics Data System (ADS)

Sandler, Roman A.; Song, Dong; Hampson, Robert E.; Deadwyler, Sam A.; Berger, Theodore W.; Marmarelis, Vasilis Z.

2015-10-01

Objective. Traditional hippocampal modeling has focused on the series of feedforward synapses known as the trisynaptic pathway. However, feedback connections from CA1 back to the hippocampus through the entorhinal cortex (EC) actually make the hippocampus a closed-loop system. By constructing a functional closed-loop model of the hippocampus, one may learn how both physiological and epileptic oscillations emerge and design efficient neurostimulation patterns to abate such oscillations. Approach. Point process input-output models where estimated from recorded rodent hippocampal data to describe the nonlinear dynamical transformation from CA3 → CA1, via the schaffer-collateral synapse, and CA1 → CA3 via the EC. Each Volterra-like subsystem was composed of linear dynamics (principal dynamic modes) followed by static nonlinearities. The two subsystems were then wired together to produce the full closed-loop model of the hippocampus. Main results. Closed-loop connectivity was found to be necessary for the emergence of theta resonances as seen in recorded data, thus validating the model. The model was then used to identify frequency parameters for the design of neurostimulation patterns to abate seizures. Significance. Deep-brain stimulation (DBS) is a new and promising therapy for intractable seizures. Currently, there is no efficient way to determine optimal frequency parameters for DBS, or even whether periodic or broadband stimuli are optimal. Data-based computational models have the potential to be used as a testbed for designing optimal DBS patterns for individual patients. However, in order for these models to be successful they must incorporate the complex closed-loop structure of the seizure focus. This study serves as a proof-of-concept of using such models to design efficient personalized DBS patterns for epilepsy.

Hippocampal closed-loop modeling and implications for seizure stimulation design.

PubMed

Sandler, Roman A; Song, Dong; Hampson, Robert E; Deadwyler, Sam A; Berger, Theodore W; Marmarelis, Vasilis Z

2015-10-01

Traditional hippocampal modeling has focused on the series of feedforward synapses known as the trisynaptic pathway. However, feedback connections from CA1 back to the hippocampus through the entorhinal cortex (EC) actually make the hippocampus a closed-loop system. By constructing a functional closed-loop model of the hippocampus, one may learn how both physiological and epileptic oscillations emerge and design efficient neurostimulation patterns to abate such oscillations. Point process input-output models where estimated from recorded rodent hippocampal data to describe the nonlinear dynamical transformation from CA3 → CA1, via the schaffer-collateral synapse, and CA1 → CA3 via the EC. Each Volterra-like subsystem was composed of linear dynamics (principal dynamic modes) followed by static nonlinearities. The two subsystems were then wired together to produce the full closed-loop model of the hippocampus. Closed-loop connectivity was found to be necessary for the emergence of theta resonances as seen in recorded data, thus validating the model. The model was then used to identify frequency parameters for the design of neurostimulation patterns to abate seizures. Deep-brain stimulation (DBS) is a new and promising therapy for intractable seizures. Currently, there is no efficient way to determine optimal frequency parameters for DBS, or even whether periodic or broadband stimuli are optimal. Data-based computational models have the potential to be used as a testbed for designing optimal DBS patterns for individual patients. However, in order for these models to be successful they must incorporate the complex closed-loop structure of the seizure focus. This study serves as a proof-of-concept of using such models to design efficient personalized DBS patterns for epilepsy.

Hippocampal Closed-Loop Modeling and Implications for Seizure Stimulation Design

PubMed Central

Sandler, Roman A.; Song, Dong; Hampson, Robert E.; Deadwyler, Sam A.; Berger, Theodore W.; Marmarelis, Vasilis Z.

2016-01-01

Objective Traditional hippocampal modeling has focused on the series of feedforward synapses known as the trisynaptic pathway. However, feedback connections from CA1 back to the hippocampus through the Entorhinal Cortex (EC) actually make the hippocampus a closed-loop system. By constructing a functional closed-loop model of the hippocampus, one may learn how both physiological and epileptic oscillations emerge and design efficient neurostimulation patterns to abate such oscillations. Approach Point process input-output models where estimated from recorded rodent hippocampal data to describe the nonlinear dynamical transformation from CA3→CA1, via the Schaffer-Collateral synapse, and CA1→CA3 via the EC. Each Volterra-like subsystem was composed of linear dynamics (Principal Dynamic Modes) followed by static nonlinearities. The two subsystems were then wired together to produce the full closed-loop model of the hippocampus. Main Results Closed-loop connectivity was found to be necessary for the emergence of theta resonances as seen in recorded data, thus validating the model. The model was then used to identify frequency parameters for the design of neurostimulation patterns to abate seizures. Significance DBS is a new and promising therapy for intractable seizures. Currently, there is no efficient way to determine optimal frequency parameters for DBS, or even whether periodic or broadband stimuli are optimal. Data-based computational models have the potential to be used as a testbed for designing optimal DBS patterns for individual patients. However, in order for these models to be successful they must incorporate the complex closed-loop structure of the seizure focus. This study serves as a proof-of-concept of using such models to design efficient personalized DBS patterns for epilepsy. PMID:26355815

Similarity Metrics for Closed Loop Dynamic Systems

NASA Technical Reports Server (NTRS)

Whorton, Mark S.; Yang, Lee C.; Bedrossian, Naz; Hall, Robert A.

2008-01-01

To what extent and in what ways can two closed-loop dynamic systems be said to be "similar?" This question arises in a wide range of dynamic systems modeling and control system design applications. For example, bounds on error models are fundamental to the controller optimization with modern control design methods. Metrics such as the structured singular value are direct measures of the degree to which properties such as stability or performance are maintained in the presence of specified uncertainties or variations in the plant model. Similarly, controls-related areas such as system identification, model reduction, and experimental model validation employ measures of similarity between multiple realizations of a dynamic system. Each area has its tools and approaches, with each tool more or less suited for one application or the other. Similarity in the context of closed-loop model validation via flight test is subtly different from error measures in the typical controls oriented application. Whereas similarity in a robust control context relates to plant variation and the attendant affect on stability and performance, in this context similarity metrics are sought that assess the relevance of a dynamic system test for the purpose of validating the stability and performance of a "similar" dynamic system. Similarity in the context of system identification is much more relevant than are robust control analogies in that errors between one dynamic system (the test article) and another (the nominal "design" model) are sought for the purpose of bounding the validity of a model for control design and analysis. Yet system identification typically involves open-loop plant models which are independent of the control system (with the exception of limited developments in closed-loop system identification which is nonetheless focused on obtaining open-loop plant models from closed-loop data). Moreover the objectives of system identification are not the same as a flight test and hence system identification error metrics are not directly relevant. In applications such as launch vehicles where the open loop plant is unstable it is similarity of the closed-loop system dynamics of a flight test that are relevant.

RELAP5 Analysis of the Hybrid Loop-Pool Design for Sodium Cooled Fast Reactors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hongbin Zhang; Haihua Zhao; Cliff Davis

2008-06-01

An innovative hybrid loop-pool design for sodium cooled fast reactors (SFR-Hybrid) has been recently proposed. This design takes advantage of the inherent safety of a pool design and the compactness of a loop design to improve economics and safety of SFRs. In the hybrid loop-pool design, primary loops are formed by connecting the reactor outlet plenum (hot pool), intermediate heat exchangers (IHX), primary pumps and the reactor inlet plenum with pipes. The primary loops are immersed in the cold pool (buffer pool). Passive safety systems -- modular Pool Reactor Auxiliary Cooling Systems (PRACS) – are added to transfer decay heatmore » from the primary system to the buffer pool during loss of forced circulation (LOFC) transients. The primary systems and the buffer pool are thermally coupled by the PRACS, which is composed of PRACS heat exchangers (PHX), fluidic diodes and connecting pipes. Fluidic diodes are simple, passive devices that provide large flow resistance in one direction and small flow resistance in reverse direction. Direct reactor auxiliary cooling system (DRACS) heat exchangers (DHX) are immersed in the cold pool to transfer decay heat to the environment by natural circulation. To prove the design concepts, especially how the passive safety systems behave during transients such as LOFC with scram, a RELAP5-3D model for the hybrid loop-pool design was developed. The simulations were done for both steady-state and transient conditions. This paper presents the details of RELAP5-3D analysis as well as the calculated thermal response during LOFC with scram. The 250 MW thermal power conventional pool type design of GNEP’s Advanced Burner Test Reactor (ABTR) developed by Argonne National Laboratory was used as the reference reactor core and primary loop design. The reactor inlet temperature is 355 °C and the outlet temperature is 510 °C. The core design is the same as that for ABTR. The steady state buffer pool temperature is the same as the reactor inlet temperature. The peak cladding, hot pool, cold pool and reactor inlet temperatures were calculated during LOFC. The results indicate that there are two phases during LOFC transient – the initial thermal equilibration phase and the long term decay heat removal phase. The initial thermal equilibration phase occurs over a few hundred seconds, as the system adjusts from forced circulation to natural circulation flow. Subsequently, during long-term heat removal phase all temperatures evolve very slowly due to the large thermal inertia of the primary and buffer pool systems. The results clearly show that passive safety PRACS can effectively transfer decay heat from the primary system to the buffer pool by natural circulation. The DRACS system in turn can effectively transfer the decay heat to the environment.« less

Optimal cooperative control synthesis of active displays

NASA Technical Reports Server (NTRS)

Garg, S.; Schmidt, D. K.

1985-01-01

A technique is developed that is intended to provide a systematic approach to synthesizing display augmentation for optimal manual control in complex, closed-loop tasks. A cooperative control synthesis technique, previously developed to design pilot-optimal control augmentation for the plant, is extended to incorporate the simultaneous design of performance enhancing displays. The technique utilizes an optimal control model of the man in the loop. It is applied to the design of a quickening control law for a display and a simple K/s(2) plant, and then to an F-15 type aircraft in a multi-channel task. Utilizing the closed loop modeling and analysis procedures, the results from the display design algorithm are evaluated and an analytical validation is performed. Experimental validation is recommended for future efforts.

The use of loop-seals for the control of the overpressures in hydraulic transients evolving in a sea service water system

NASA Astrophysics Data System (ADS)

Canetta, D.; Capozza, A.; Iovino, G.

The transient response following pump trip-offs and start-ups was investigated in the sea water system of a nuclear power plant. Specific care was devoted to water column separation and cavity collapse phenomena. A computer program designed for analysis of complex hydraulic networks was used. It is found that dangerous overpressures can be avoided by the use of loop seals. The design of the vacuum breaker valves of the loop seals and the optimization of overall transient behavior is discussed.

Trajectory Design Enhancements to Mitigate Risk for the Transiting Exoplanet Survey Satellite (TESS)

NASA Technical Reports Server (NTRS)

Dichmann, Donald; Parker, Joel; Nickel, Craig; Lutz, Stephen

2016-01-01

The Transiting Exoplanet Survey Satellite (TESS) will employ a highly eccentric Earth orbit, in 2:1 lunar resonance, which will be reached with a lunar flyby preceded by 3.5 phasing loops. The TESS mission has limited propellant and several constraints on the science orbit and on the phasing loops. Based on analysis and simulation, we have designed the phasing loops to reduce delta-V (DV) and to mitigate risk due to maneuver execution errors. We have automated the trajectory design process and use distributed processing to generate and optimal nominal trajectories; to check constraint satisfaction; and finally to model the effects of maneuver errors to identify trajectories that best meet the mission requirements.

Study of the effect of loop inductance on the RF transmission line to cavity coupling coefficient

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lal, Shankar, E-mail: shankar@rrcat.gov.in; Pant, K. K.

2016-08-15

Coupling of RF power is an important aspect in the design and development of RF accelerating structures. RF power coupling employing coupler loops has the advantage of tunability of β, the transmission line to cavity coupling coefficient. Analytical expressions available in literature for determination of size of the coupler loop using Faraday’s law of induction show reasonably good agreement with experimentally measured values of β below critical coupling (β ≤ 1) but show large deviation with experimentally measured values and predictions by simulations for higher values of β. In actual accelerator application, many RF cavities need to be over-coupled withmore » β > 1 for reasons of beam loading compensation, reduction of cavity filling time, etc. This paper discusses a modified analytical formulation by including the effect of loop inductance in the determination of loop size for any desired coupling coefficient. The analytical formulation shows good agreement with 3D simulations and with experimentally measured values. It has been successfully qualified by the design and development of power coupler loops for two 476 MHz pre-buncher RF cavities, which have successfully been conditioned at rated power levels using these coupler loops.« less

Study of the effect of loop inductance on the RF transmission line to cavity coupling coefficient

NASA Astrophysics Data System (ADS)

Lal, Shankar; Pant, K. K.

2016-08-01

Coupling of RF power is an important aspect in the design and development of RF accelerating structures. RF power coupling employing coupler loops has the advantage of tunability of β, the transmission line to cavity coupling coefficient. Analytical expressions available in literature for determination of size of the coupler loop using Faraday's law of induction show reasonably good agreement with experimentally measured values of β below critical coupling (β ≤ 1) but show large deviation with experimentally measured values and predictions by simulations for higher values of β. In actual accelerator application, many RF cavities need to be over-coupled with β > 1 for reasons of beam loading compensation, reduction of cavity filling time, etc. This paper discusses a modified analytical formulation by including the effect of loop inductance in the determination of loop size for any desired coupling coefficient. The analytical formulation shows good agreement with 3D simulations and with experimentally measured values. It has been successfully qualified by the design and development of power coupler loops for two 476 MHz pre-buncher RF cavities, which have successfully been conditioned at rated power levels using these coupler loops.

Enhanced Performance Controller Design for Stochastic Systems by Adding Extra State Estimation onto the Existing Closed Loop Control

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Yuyang; Zhang, Qichun; Wang, Hong

To enhance the performance of the tracking property , this paper presents a novel control algorithm for a class of linear dynamic stochastic systems with unmeasurable states, where the performance enhancement loop is established based on Kalman filter. Without changing the existing closed loop with the PI controller, the compensative controller is designed to minimize the variances of the tracking errors using the estimated states and the propagation of state variances. Moreover, the stability of the closed-loop systems has been analyzed in the mean-square sense. A simulated example is included to show the effectiveness of the presented control algorithm, wheremore » encouraging results have been obtained.« less

A Robust H ∞ Controller for an UAV Flight Control System.

PubMed

López, J; Dormido, R; Dormido, S; Gómez, J P

2015-01-01

The objective of this paper is the implementation and validation of a robust H ∞ controller for an UAV to track all types of manoeuvres in the presence of noisy environment. A robust inner-outer loop strategy is implemented. To design the H ∞ robust controller in the inner loop, H ∞ control methodology is used. The two controllers that conform the outer loop are designed using the H ∞ Loop Shaping technique. The reference vector used in the control architecture formed by vertical velocity, true airspeed, and heading angle, suggests a nontraditional way to pilot the aircraft. The simulation results show that the proposed control scheme works well despite the presence of noise and uncertainties, so the control system satisfies the requirements.

Loop-mediated isothermal amplification for detection of the tomato and potato late blight pathogen, Phytophthora infestans

USDA-ARS?s Scientific Manuscript database

Aims: To design and validate a colorimetric loop-mediated isothermal amplification assay for rapid detection of P. infestans DNA. Methods and Results: Two sets of LAMP primers were designed and evaluated for their sensitivity and specificity for P. infestans. ITSII primers targeted a portion of the ...

A 7T spine array based on electric dipole transmitters.

PubMed

Duan, Qi; Nair, Govind; Gudino, Natalia; de Zwart, Jacco A; van Gelderen, Peter; Murphy-Boesch, Joe; Reich, Daniel S; Duyn, Jeff H; Merkle, Hellmut

2015-10-01

The goal of this study was to explore the feasibility of using an array of electric dipole antennas for RF transmission in spine MRI at high fields. A two-channel transmit array based on an electric dipole design was quantitatively optimized for 7T spine imaging and integrated with a receive array combining eight loop coils. Using B1+ mapping, the transmit efficiency of the dipole array was compared with a design using quadrature loop pairs. The radiofrequency energy deposition for each array was measured using a home-built dielectric phantom and MR thermometry. The performance of the proposed array was qualitatively demonstrated in human studies. The results indicate dramatically improved transmit efficiency for the dipole design compared with the loop excitation. A gain of up to 76% was achieved within the spinal region. For imaging of the spine, electric dipole-based transmitters provide an attractive alternative to the traditional loop-based design. Easy integration with existing receive array technology facilitates practical use at high fields. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Utilization of a Vehicle Integrated Intelligence (V(INT)2) System in Armor Units

DTIC Science & Technology

1984-04-01

weaknesses or deficiencies in the plan such as blind spots or fire integration plans likely to result in either overkill or underkill (e.g., gaps). The...movement is used with this formation. 108 A PL TI.I TK2 . *Thiso~ A oiiaini sdweee h Figue 5-4. CmbatWedg PLL PS I 10 M4w ;ok *Thi modificatio isue-heee-h

Molecular Dynamics of Lipid Bilayers

DTIC Science & Technology

1989-08-09

34 ECZI~ NUMUER 01" O-USECNI’ONS) Vt5 DEGRLU: LOOEi-00(PICOSEC Z-ILIO Pfu .LC 2 I 2 Ni, I AlI I 1-.M U 1 l"M .111 p lPll..4 5~~~~ 93.U) i’(OU...Station Box 3944 Laramie, WY 82071 LINDSAY, Stuart M. RACKOVSKY, Shalom R. SINSKEY, Anthony J. Department of Physics Department of Biophysics

Design and Control of a Closed-Loop Brushless Torque Activator

DTIC Science & Technology

1990-05-01

AD-A270 760 Technical Report 1244 Design and Control of a Closed-Loop Brushless Torque Activator Michael Dean Levi MIT Artificial Intelligence... Brushless N00014-86-K-0685 Torque Actuator 6. AUTHOR(S) Michael Dean Levin 7. PERFORMING ORGANIZATION NAME(S) AND ADORESS(ES) B. PERFORMING...200 words) This’report explores the design and control issues associated with a brushless actuator capable of achieving extremely high torque

System and method of designing models in a feedback loop

DOEpatents

Gosink, Luke C.; Pulsipher, Trenton C.; Sego, Landon H.

2017-02-14

A method and system for designing models is disclosed. The method includes selecting a plurality of models for modeling a common event of interest. The method further includes aggregating the results of the models and analyzing each model compared to the aggregate result to obtain comparative information. The method also includes providing the information back to the plurality of models to design more accurate models through a feedback loop.

Aircraft flight test trajectory control

NASA Technical Reports Server (NTRS)

Menon, P. K. A.; Walker, R. A.

1988-01-01

Two control law design techniques are compared and the performance of the resulting controllers evaluated. The design requirement is for a flight test trajectory controller (FTTC) capable of closed-loop, outer-loop control of an F-15 aircraft performing high-quality research flight test maneuvers. The maneuver modeling, linearization, and design methodologies utilized in this research, are detailed. The results of applying these FTTCs to a nonlinear F-15 simulation are presented.

Mechanosensory organ regeneration in zebrafish depends on a population of multipotent progenitor cells kept latent by Schwann cells.

PubMed

Sánchez, Mario; Ceci, Maria Laura; Gutiérrez, Daniela; Anguita-Salinas, Consuelo; Allende, Miguel L

2016-04-07

Regenerating damaged tissue is a complex process, requiring progenitor cells that must be stimulated to undergo proliferation, differentiation and, often, migratory behaviors and morphological changes. Multiple cell types, both resident within the damaged tissue and recruited to the lesion site, have been shown to participate. However, the cellular and molecular mechanisms involved in the activation of progenitor cell proliferation and differentiation after injury, and their regulation by different cells types, are not fully understood. The zebrafish lateral line is a suitable system to study regeneration because most of its components are fully restored after damage. The posterior lateral line (PLL) is a mechanosensory system that develops embryonically and is initially composed of seven to eight neuromasts distributed along the trunk and tail, connected by a continuous stripe of interneuromastic cells (INCs). The INCs remain in a quiescent state owing to the presence of underlying Schwann cells. They become activated during development to form intercalary neuromasts. However, no studies have described if INCs can participate in a regenerative event, for example, after the total loss of a neuromast. We used electroablation in transgenic larvae expressing fluorescent proteins in PLL components to completely ablate single neuromasts in larvae and adult fish. This injury results in discontinuity of the INCs, Schwann cells, and the PLL nerve. In vivo imaging showed that the INCs fill the gap left after the injury and can regenerate a new neuromast in the injury zone. Further, a single INC is able to divide and form all cell types in a regenerated neuromast and, during this process, it transiently expresses the sox2 gene, a neural progenitor cell marker. We demonstrate a critical role for Schwann cells as negative regulators of INC proliferation and neuromast regeneration, and that this inhibitory property is completely dependent on active ErbB signaling. The potential to regenerate a neuromast after damage requires that progenitor cells (INCs) be temporarily released from an inhibitory signal produced by nearby Schwann cells. This simple yet highly effective two-component niche offers the animal robust mechanisms for organ growth and regeneration, which can be sustained throughout life.

Gradiometer Using Middle Loops as Sensing Elements in a Low-Field SQUID MRI System

NASA Technical Reports Server (NTRS)

Penanen, Konstantin; Hahn, Inseob; Ho Eom, Byeong

2009-01-01

A new gradiometer scheme uses middle loops as sensing elements in lowfield superconducting quantum interference device (SQUID) magnetic resonance imaging (MRI). This design of a second order gradiometer increases its sensitivity and makes it more uniform, compared to the conventional side loop sensing scheme with a comparable matching SQUID. The space between the two middle loops becomes the imaging volume with the enclosing cryostat built accordingly.

Advanced rotorcraft control using parameter optimization

NASA Technical Reports Server (NTRS)

Vansteenwyk, Brett; Ly, Uy-Loi

1991-01-01

A reliable algorithm for the evaluation of a quadratic performance index and its gradients with respect to the controller design parameters is presented. The algorithm is part of a design algorithm for an optimal linear dynamic output feedback controller that minimizes a finite time quadratic performance index. The numerical scheme is particularly robust when it is applied to the control law synthesis for systems with densely packed modes and where there is a high likelihood of encountering degeneracies in the closed loop eigensystem. This approach through the use of a accurate Pade series approximation does not require the closed loop system matrix to be diagonalizable. The algorithm has been included in a control design package for optimal robust low order controllers. Usefulness of the proposed numerical algorithm has been demonstrated using numerous practical design cases where degeneracies occur frequently in the closed loop system under an arbitrary controller design initialization and during the numerical search.

The pH-dependent tertiary structure of a designed helix-loop-helix dimer.

PubMed

Dolphin, G T; Baltzer, L

1997-01-01

De novo designed helix-loop-helix motifs can fold into well-defined tertiary structures if residues or groups of residues are incorporated at the helix-helix boundary to form helix-recognition sites that restrict the conformational degrees of freedom of the helical segments. Understanding the relationship between structure and function of conformational constraints therefore forms the basis for the engineering of non-natural proteins. This paper describes the design of an interhelical HisH+-Asp- hydrogen-bonded ion pair and the conformational stability of the folded helix-loop-helix motif. GTD-C, a polypeptide with 43 amino acid residues, has been designed to fold into a hairpin helix-loop-helix motif that can dimerise to form a four-helix bundle. The folded motif is in slow conformational exchange on the NMR timescale and has a well-dispersed 1H NMR spectrum, a narrow temperature interval for thermal denaturation and a near-UV CD spectrum with some fine structure. The conformational stability is pH dependent with an optimum that corresponds to the pH for maximum formation of a hydrogen-bonded ion pair between HisH17+ in helix I and Asp27- in helix II. The formation of an interhelical salt bridge is strongly suggested by the pH dependence of a number of spectroscopic probes to generate a well-defined tertiary structure in a designed helix-loop-helix motif. The thermodynamic stability of the folded motif is not increased by the formation of the salt bridge, but neighbouring conformations are destabilised. The use of this novel design principle in combination with hydrophobic interactions that provide sufficient binding energy in the folded structure should be of general use in de novo design of native-like proteins.

Activation loop targeting strategy for design of receptor-interacting protein kinase 2 (RIPK2) inhibitors.

PubMed

Suebsuwong, Chalada; Pinkas, Daniel M; Ray, Soumya S; Bufton, Joshua C; Dai, Bing; Bullock, Alex N; Degterev, Alexei; Cuny, Gregory D

2018-02-15

Development of selective kinase inhibitors remains a challenge due to considerable amino acid sequence similarity among family members particularly in the ATP binding site. Targeting the activation loop might offer improved inhibitor selectivity since this region of kinases is less conserved. However, the strategy presents difficulties due to activation loop flexibility. Herein, we report the design of receptor-interacting protein kinase 2 (RIPK2) inhibitors based on pan-kinase inhibitor regorafenib that aim to engage basic activation loop residues Lys169 or Arg171. We report development of CSR35 that displayed >10-fold selective inhibition of RIPK2 versus VEGFR2, the target of regorafenib. A co-crystal structure of CSR35 with RIPK2 revealed a resolved activation loop with an ionic interaction between the carboxylic acid installed in the inhibitor and the side-chain of Lys169. Our data provides principle feasibility of developing activation loop targeting type II inhibitors as a complementary strategy for achieving improved selectivity. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.