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Sample records for analog ic designed

  1. Placement with Symmetry Constraints for Analog IC Layout Design Based on Tree Representation

    NASA Astrophysics Data System (ADS)

    Hirakawa, Natsumi; Fujiyoshi, Kunihiro

    Symmetry constrains are the constraints that the given cells should be placed symmetrically in design of analog ICs. We use O-tree to represent placements and propose a decoding algorithm which can obtain one of the minimum placements satisfying the constraints. The decoding algorithm uses linear programming, which is too much time consuming. Therefore we propose a graph based method to recognize if there exists no placement satisfying both the given symmetry and O-tree constraints, and use the method before application of linear programming. The effectiveness of the proposed method was shown by computational experiments.

  2. A reuse-based framework for the design of analog and mixed-signal ICs

    NASA Astrophysics Data System (ADS)

    Castro-Lopez, Rafael; Fernandez, Francisco V.; Rodriguez Vazquez, Angel

    2005-06-01

    Despite the spectacular breakthroughs of the semiconductor industry, the ability to design integrated circuits (ICs) under stringent time-to-market (TTM) requirements is lagging behind integration capacity, so far keeping pace with still valid Moore"s Law. The resulting gap is threatening with slowing down such a phenomenal growth. The design community believes that it is only by means of powerful CAD tools and design methodologies - and, possibly, a design paradigm shift - that this design gap can be bridged. In this sense, reuse-based design is seen as a promising solution, and concepts such as IP Block, Virtual Component, and Design Reuse have become commonplace thanks to the significant advances in the digital arena. Unfortunately, the very nature of analog and mixed-signal (AMS) design has hindered a similar level of consensus and development. This paper presents a framework for the reuse-based design of AMS circuits. The framework is founded on three key elements: (1) a CAD-supported hierarchical design flow that facilitates the incorporation of AMS reusable blocks, reduces the overall design time, and expedites the management of increasing AMS design complexity; (2) a complete, clear definition of the AMS reusable block, structured into three separate facets or views: the behavioral, structural, and layout facets, the two first for top-down electrical synthesis and bottom-up verification, the latter used during bottom-up physical synthesis; (3) the design for reusability set of tools, methods, and guidelines that, relying on intensive parameterization as well as on design knowledge capture and encapsulation, allows to produce fully reusable AMS blocks. A case study and a functional silicon prototype demonstrate the validity of the paper"s proposals.

  3. IC quadrature filters for analog multipliers

    NASA Astrophysics Data System (ADS)

    Tarasov, V. P.; Timonteev, V. N.

    1980-08-01

    The paper considers the design of symmetric and asymmetric quadrature filters. Formulas are presented for transfer functions, nonlinear distortions, q-factor, and dynamic range for different filter connections in the direct-transmission channels. The integrated design of a highpass quadrature filter is considered.

  4. Multichannel analog front-end and analog-to-digital converter ICs for silicon photomultipliers

    NASA Astrophysics Data System (ADS)

    Bocharov, Y. I.; Butuzov, V. A.

    2016-10-01

    Integrated circuit (IC) of multichannel analog front-end and a mixed-signal chip of multichannel analog-to-digital converter are presented. A chipset of these two ICs is intended for readout, analog preprocessing and analog to digital conversion of silicon photomultiplier array signals. The number of channels of the analog front-end IC as well as the types of their input stages depends on the application. The current test version of the chip contains three current-input channels and three voltage-input channels. Each of the channels includes a programmable pre-amplifier, integrator with baseline-holder, code-controlled amplifier, amplitude discriminator, two programmable timers, pulse-shaping low-pass filter, peak detector, and an output buffer with baseline tuning circuitry. The analog IC has code-configurable architecture. The mixed-signal IC includes nine main channels and one auxiliary channel, containing 10-bit analog-to-digital converter in each channel. It also has a buffer memory and a voltage reference. The chip features low power consumption, which is less than 0.5 mW per channel at a sampling rate of 100 kHz. Both ICs are implemented in 0.35 μm CMOS technology.

  5. Fully Integrated Biopotential Acquisition Analog Front-End IC.

    PubMed

    Song, Haryong; Park, Yunjong; Kim, Hyungseup; Ko, Hyoungho

    2015-09-30

    A biopotential acquisition analog front-end (AFE) integrated circuit (IC) is presented. The biopotential AFE includes a capacitively coupled chopper instrumentation amplifier (CCIA) to achieve low input referred noise (IRN) and to block unwanted DC potential signals. A DC servo loop (DSL) is designed to minimize the offset voltage in the chopper amplifier and low frequency respiration artifacts. An AC coupled ripple rejection loop (RRL) is employed to reduce ripple due to chopper stabilization. A capacitive impedance boosting loop (CIBL) is designed to enhance the input impedance and common mode rejection ratio (CMRR) without additional power consumption, even under an external electrode mismatch. The AFE IC consists of two-stage CCIA that include three compensation loops (DSL, RRL, and CIBL) at each CCIA stage. The biopotential AFE is fabricated using a 0.18 μm one polysilicon and six metal layers (1P6M) complementary metal oxide semiconductor (CMOS) process. The core chip size of the AFE without input/output (I/O) pads is 10.5 mm². A fourth-order band-pass filter (BPF) with a pass-band in the band-width from 1 Hz to 100 Hz was integrated to attenuate unwanted signal and noise. The overall gain and band-width are reconfigurable by using programmable capacitors. The IRN is measured to be 0.94 μVRMS in the pass band. The maximum amplifying gain of the pass-band was measured as 71.9 dB. The CIBL enhances the CMRR from 57.9 dB to 67 dB at 60 Hz under electrode mismatch conditions.

  6. Fully Integrated Biopotential Acquisition Analog Front-End IC

    PubMed Central

    Song, Haryong; Park, Yunjong; Kim, Hyungseup; Ko, Hyoungho

    2015-01-01

    A biopotential acquisition analog front-end (AFE) integrated circuit (IC) is presented. The biopotential AFE includes a capacitively coupled chopper instrumentation amplifier (CCIA) to achieve low input referred noise (IRN) and to block unwanted DC potential signals. A DC servo loop (DSL) is designed to minimize the offset voltage in the chopper amplifier and low frequency respiration artifacts. An AC coupled ripple rejection loop (RRL) is employed to reduce ripple due to chopper stabilization. A capacitive impedance boosting loop (CIBL) is designed to enhance the input impedance and common mode rejection ratio (CMRR) without additional power consumption, even under an external electrode mismatch. The AFE IC consists of two-stage CCIA that include three compensation loops (DSL, RRL, and CIBL) at each CCIA stage. The biopotential AFE is fabricated using a 0.18 µm one polysilicon and six metal layers (1P6M) complementary metal oxide semiconductor (CMOS) process. The core chip size of the AFE without input/output (I/O) pads is 10.5 mm2. A fourth-order band-pass filter (BPF) with a pass-band in the band-width from 1 Hz to 100 Hz was integrated to attenuate unwanted signal and noise. The overall gain and band-width are reconfigurable by using programmable capacitors. The IRN is measured to be 0.94 µVRMS in the pass band. The maximum amplifying gain of the pass-band was measured as 71.9 dB. The CIBL enhances the CMRR from 57.9 dB to 67 dB at 60 Hz under electrode mismatch conditions. PMID:26437404

  7. Study of proton radiation effects on analog IC designed for high energy physics in a BICMOS-JFET radhard SOI technology

    SciTech Connect

    Blanquart, L.; Delpierre, P.; Habrard, M.C.

    1994-12-01

    The authors present experimental results from a fast charge amplifier and a wideband analog buffer processed in the DMILL BiCMOS-JFET radhard SOI technology and irradiated up to 4.5 {times} 10{sup 14} protons/cm{sup 2}. In parallel, they have irradiated elementary transistors. These components were biased and electrical measurements were done 30 min after beam stop. By evaluating variations of main SPICE parameters, i.e., threshold voltage shift for CMOS and current gain variation for bipolar transistors, they have simulated the wideband analog buffer at different doses. These SPICE simulations are in good agreement with measured circuit degradations. The behavior of the charge amplifier is consistent with extraction of transconductance and pinch-off voltage shift of the PJFET.

  8. Analog/digital pH meter system I.C.

    NASA Technical Reports Server (NTRS)

    Vincent, Paul; Park, Jea

    1992-01-01

    The project utilizes design automation software tools to design, simulate, and fabricate a pH meter integrated circuit (IC) system including a successive approximation type seven-bit analog to digital converter circuits using a 1.25 micron N-Well CMOS MOSIS process. The input voltage ranges from 0.5 to 1.0 V derived from a special type pH sensor, and the output is a three-digit decimal number display of pH with one decimal point.

  9. Azimuth correlator design for IC chip

    NASA Technical Reports Server (NTRS)

    Tyree, V. C.; Wu, C.

    1980-01-01

    Azimuth correlator circuit synthetic-aperature radar (SAR) is designed for single integrated circuit (IC) chip. Azimuth correlator modules constructed with sets of such chips could make real-time signal processing possible. Primary advantages are realized in areas of weight and power requirement reductions.

  10. A Way to End the IC Designer Shortage.

    ERIC Educational Resources Information Center

    Robinson, Arthur L.

    1980-01-01

    Discusses the problem of the shortage of engineers capable of designing advanced integrated circuits (IC) and presents some suggestions for increasing the number of IC designers in universities and semiconductor companies. (HM)

  11. A Way to End the IC Designer Shortage.

    ERIC Educational Resources Information Center

    Robinson, Arthur L.

    1980-01-01

    Discusses the problem of the shortage of engineers capable of designing advanced integrated circuits (IC) and presents some suggestions for increasing the number of IC designers in universities and semiconductor companies. (HM)

  12. Neural recording front-end IC using action potential detection and analog buffer with digital delay for data compression.

    PubMed

    Liu, Lei; Yao, Lei; Zou, Xiaodan; Goh, Wang Ling; Je, Minkyu

    2013-01-01

    This paper presents a neural recording analog front-end IC intended for simultaneous neural recording with action potential (AP) detection for data compression in wireless multichannel neural implants. The proposed neural recording front-end IC detects the neural spikes and sends only the preserved AP information for wireless transmission in order to reduce the overall power consumption of the neural implant. The IC consists of a low-noise neural amplifier, an AP detection circuit and an analog buffer with digital delay. The neural amplifier makes use of a current-reuse technique to maximize the transconductance efficiency for attaining a good noise efficiency factor. The AP detection circuit uses an adaptive threshold voltage to generate an enable signal for the subsequent functional blocks. The analog buffer with digital delay is employed using a finite impulse response (FIR) filter which preserves the AP waveform before the enable signal as well as provides low-pass filtering. The neural recording front-end IC has been designed using standard CMOS 0.18-µm technology occupying a core area of 220 µm by 820 µm.

  13. Design of high speed LVDS transceiver ICs

    NASA Astrophysics Data System (ADS)

    Jian, Xu; Zhigong, Wang; Xiaokang, Niu

    2010-07-01

    The design of low-power LVDS (low voltage differential signaling) transceiver ICs is presented. The LVDS transmitter integrates a common-mode feedback control on chip, while a specially designed pre-charge circuit is proposed to improve the speed of the circuit, making the highest data rate up to 622 Mb/s. For the LVDS receiver design, the performance degradation issues are solved when handling the large input common mode voltages of the conventional LVDS receivers. In addition, the LVDS receiver also supports the failsafe function. The transceiver chips were verified with the CSMC 0.5-μm CMOS process. The measured results showed that, for the LVDS transmitter with the pre-charge technique proposed, the maximum data rate is higher than 622 Mb/s. The power consumption is 6 mA with a 5-V power supply. The LVDS receiver can work properly with a larger input common mode voltage (0.1-2.4 V) but a differential input voltage as low as 100 mV. The power consumption is only 1.2 mA with a 5-V supply at the highest data rate of 400 Mb/s. The chip set meets the TIA/EIA-644-A standards and shows its potential prospects in LVDS transmission systems.

  14. A Novel Analog Integrated Circuit Design Course Covering Design, Layout, and Resulting Chip Measurement

    ERIC Educational Resources Information Center

    Lin, Wei-Liang; Cheng, Wang-Chuan; Wu, Chen-Hao; Wu, Hai-Ming; Wu, Chang-Yu; Ho, Kuan-Hsuan; Chan, Chueh-An

    2010-01-01

    This work describes a novel, first-year graduate-level analog integrated circuit (IC) design course. The course teaches students analog circuit design; an external manufacturer then produces their designs in three different silicon chips. The students, working in pairs, then test these chips to verify their success. All work is completed within…

  15. A Novel Analog Integrated Circuit Design Course Covering Design, Layout, and Resulting Chip Measurement

    ERIC Educational Resources Information Center

    Lin, Wei-Liang; Cheng, Wang-Chuan; Wu, Chen-Hao; Wu, Hai-Ming; Wu, Chang-Yu; Ho, Kuan-Hsuan; Chan, Chueh-An

    2010-01-01

    This work describes a novel, first-year graduate-level analog integrated circuit (IC) design course. The course teaches students analog circuit design; an external manufacturer then produces their designs in three different silicon chips. The students, working in pairs, then test these chips to verify their success. All work is completed within…

  16. Automating analog design: Taming the shrew

    NASA Technical Reports Server (NTRS)

    Barlow, A.

    1990-01-01

    The pace of progress in the design of integrated circuits continues to amaze observers inside and outside of the industry. Three decades ago, a 50 transistor chip was a technological wonder. Fifteen year later, a 5000 transistor device would 'wow' the crowds. Today, 50,000 transistor chips will earn a 'not too bad' assessment, but it takes 500,000 to really leave an impression. In 1975 a typical ASIC device had 1000 transistors, took one year to first samples (and two years to production) and sold for about 5 cents per transistor. Today's 50,000 transistor gate array takes about 4 months from spec to silicon, works the first time, and sells for about 0.02 cents per transistor. Fifteen years ago, the single most laborious and error prone step in IC design was the physical layout. Today, most IC's never see the hand of a layout designer: and automatic place and route tool converts the engineer's computer captured schematic to a complete physical design using a gate array or a library of standard cells also created by software rather than by designers. CAD has also been a generous benefactor to the digital design process. The architect of today's digital systems creates the design using an RTL or other high level simulator. Then the designer pushes a button to invoke the logic synthesizer-optimizer tool. A fault analyzer checks the result for testability and suggests where scan based cells will improve test coverage. One obstinate holdout amidst this parade of progress is the automation of analog design and its reduction to semi-custom techniques. This paper investigates the application of CAD techniques to analog design.

  17. Automating analog design: Taming the shrew

    NASA Technical Reports Server (NTRS)

    Barlow, A.

    1990-01-01

    The pace of progress in the design of integrated circuits continues to amaze observers inside and outside of the industry. Three decades ago, a 50 transistor chip was a technological wonder. Fifteen year later, a 5000 transistor device would 'wow' the crowds. Today, 50,000 transistor chips will earn a 'not too bad' assessment, but it takes 500,000 to really leave an impression. In 1975 a typical ASIC device had 1000 transistors, took one year to first samples (and two years to production) and sold for about 5 cents per transistor. Today's 50,000 transistor gate array takes about 4 months from spec to silicon, works the first time, and sells for about 0.02 cents per transistor. Fifteen years ago, the single most laborious and error prone step in IC design was the physical layout. Today, most IC's never see the hand of a layout designer: and automatic place and route tool converts the engineer's computer captured schematic to a complete physical design using a gate array or a library of standard cells also created by software rather than by designers. CAD has also been a generous benefactor to the digital design process. The architect of today's digital systems creates the design using an RTL or other high level simulator. Then the designer pushes a button to invoke the logic synthesizer-optimizer tool. A fault analyzer checks the result for testability and suggests where scan based cells will improve test coverage. One obstinate holdout amidst this parade of progress is the automation of analog design and its reduction to semi-custom techniques. This paper investigates the application of CAD techniques to analog design.

  18. Application of concept selection methodology in IC process design

    NASA Astrophysics Data System (ADS)

    Kim, Myung-Kul

    1993-01-01

    Search for an effective methodology practical in IC manufacturing process development led to trial of quantitative 'concept selection' methodology in selecting the 'best' alternative for interlevel dielectric (ILD) processes. A cross-functional team selected multi-criteria with scoring guidelines to be used in the definition of the 'best'. The project was targeted for the 3 level metal backend process for sub-micron gate array product. The outcome of the project showed that the maturity of the alternatives has strong influence on the scores, because scores on the adopted criteria such as yield, reliability and maturity will depend on the maturity of a particular process. At the same time, the project took longer than expected since it required data for the multiple criteria. These observations suggest that adopting a simpler procedure that can analyze total inherent controllability of a process would be more effective. The methodology of the DFS (design for simplicity) tools used in analyzing the manufacturability of such electronics products as computers, phones and other consumer electronics products could be used as an 'analogy' in constructing an evaluation method for IC processes that produce devices used in those electronics products. This could be done by focusing on the basic process operation elements rather than the layers that are being built.

  19. Analog integrated circuits design for processing physiological signals.

    PubMed

    Li, Yan; Poon, Carmen C Y; Zhang, Yuan-Ting

    2010-01-01

    Analog integrated circuits (ICs) designed for processing physiological signals are important building blocks of wearable and implantable medical devices used for health monitoring or restoring lost body functions. Due to the nature of physiological signals and the corresponding application scenarios, the ICs designed for these applications should have low power consumption, low cutoff frequency, and low input-referred noise. In this paper, techniques for designing the analog front-end circuits with these three characteristics will be reviewed, including subthreshold circuits, bulk-driven MOSFETs, floating gate MOSFETs, and log-domain circuits to reduce power consumption; methods for designing fully integrated low cutoff frequency circuits; as well as chopper stabilization (CHS) and other techniques that can be used to achieve a high signal-to-noise performance. Novel applications using these techniques will also be discussed.

  20. Design techniques for low-voltage analog integrated circuits

    NASA Astrophysics Data System (ADS)

    Rakús, Matej; Stopjaková, Viera; Arbet, Daniel

    2017-08-01

    In this paper, a review and analysis of different design techniques for (ultra) low-voltage integrated circuits (IC) are performed. This analysis shows that the most suitable design methods for low-voltage analog IC design in a standard CMOS process include techniques using bulk-driven MOS transistors, dynamic threshold MOS transistors and MOS transistors operating in weak or moderate inversion regions. The main advantage of such techniques is that there is no need for any modification of standard CMOS structure or process. Basic circuit building blocks like differential amplifiers or current mirrors designed using these approaches are able to operate with the power supply voltage of 600 mV (or even lower), which is the key feature towards integrated systems for modern portable applications.

  1. Design of a 3D-IC multi-resolution digital pixel sensor

    NASA Astrophysics Data System (ADS)

    Brochard, N.; Nebhen, J.; Dubois, J.; Ginhac, D.

    2016-04-01

    This paper presents a digital pixel sensor (DPS) integrating a sigma-delta analog-to-digital converter (ADC) at pixel level. The digital pixel includes a photodiode, a delta-sigma modulation and a digital decimation filter. It features adaptive dynamic range and multiple resolutions (up to 10-bit) with a high linearity. A specific row decoder and column decoder are also designed to permit to read a specific pixel chosen in the matrix and its neighborhood of 4 x 4. Finally, a complete design with the CMOS 130 nm 3D-IC FaStack Tezzaron technology is also described, revealing a high fill-factor of about 80%.

  2. A multi-channel analog IC for in vitro neural recording

    NASA Astrophysics Data System (ADS)

    Feng, Yuan; Zhigong, Wang; Xiaoying, Lü

    2016-02-01

    Recent work in the field of neurophysiology has demonstrated that, by observing the firing characteristic of action potentials (AP) and the exchange pattern of signals between neurons, it is possible to reveal the nature of “memory” and “thinking” and help humans to understand how the brain works. To address these needs, we developed a prototype fully integrated circuit (IC) with micro-electrode array (MEA) for neural recording. In this scheme, the microelectrode array is composed by 64 detection electrodes and 2 reference electrodes. The proposed IC consists of 8 recording channels with an area of 5 × 5 mm2. Each channel can operate independently to process the neural signal by amplifying, filtering, etc. The chip is fabricated in 0.5-μm CMOS technology. The simulated and measured results show the system provides an effective device for recording feeble signal such as neural signals. Project supported by the National Natural Science Foundation of China (No. 61076118).

  3. Impact of Analog IC Impairments in SiPM Interface Electronics.

    PubMed

    Dey, Samrat; Lewellen, Thomas K; Miyaoka, Robert S; Rudell, Jacques C

    2012-01-01

    The recent realization of Silicon Photomultiplier (SiPM) devices as solid-state detectors for Positron Emission Tomography holds the promise of improving image resolution, integrating a significant portion of the interface electronics, and potentially lowering the power consumption. Our lab has previously reported on novel board-level readout electronics for an 8×8 silicon photomultiplier (SiPM) array featuring row/column summation technique to reduce the hardware requirements for signal processing and is currently working on taking the next step by implementing a monolithic CMOS chip which is based on the row-column architecture. To date, relatively little modeling has been done to understand the impact of analog non-idealities associated with the front-end electronics, on SiPM-based PET systems. This paper focuses on various analog impairments associated with PET scanner readout electronics. Matlab was used as a simulation platform to model the noise, linearity and signal bandwidth of the frontend electronics with the measured SiPM pulses as the input.

  4. A Wireless FSCV Monitoring IC with Analog Background Subtraction and UWB Telemetry

    PubMed Central

    Dorta-Quiñones, Carlos I.; Wang, Xiao Y.; Dokania, Rajeev K.; Gailey, Alycia; Lindau, Manfred; Apsel, Alyssa B.

    2015-01-01

    A 30-μW wireless fast-scan cyclic voltammetry monitoring integrated circuit for ultra-wideband (UWB) transmission of dopamine release events in freely-behaving small animals is presented. On-chip integration of analog background subtraction and UWB telemetry yields a 32-fold increase in resolution versus standard Nyquist-rate conversion alone, near a four-fold decrease in the volume of uplink data versus single-bit, third-order, delta-sigma modulation, and more than a 20-fold reduction in transmit power versus narrowband transmission for low data rates. The 1.5-mm2 chip, which was fabricated in 65-nm CMOS technology, consists of a low-noise potentiostat frontend, a two-step analog-to-digital converter (ADC), and an impulse-radio UWB transmitter (TX). The duty-cycled frontend and ADC/UWB-TX blocks draw 4 μA and 15 μA from 3-V and 1.2-V supplies, respectively. The chip achieves an input-referred current noise of 92 pArms and an input current range of ±430 nA at a conversion rate of 10 kHz. The packaged device operates from a 3-V coin-cell battery, measures 4.7 × 1.9 cm2, weighs 4.3 g (including the battery and antenna), and can be carried by small animals. The system was validated by wirelessly recording flow-injection of dopamine with concentrations in the range of 250 nM to 1 μM with a carbon-fiber microelectrode (CFM) using 300-V/s FSCV. PMID:26057983

  5. A Wireless FSCV Monitoring IC With Analog Background Subtraction and UWB Telemetry.

    PubMed

    Dorta-Quiñones, Carlos I; Wang, Xiao Y; Dokania, Rajeev K; Gailey, Alycia; Lindau, Manfred; Apsel, Alyssa B

    2016-04-01

    A 30-μW wireless fast-scan cyclic voltammetry monitoring integrated circuit for ultra-wideband (UWB) transmission of dopamine release events in freely-behaving small animals is presented. On-chip integration of analog background subtraction and UWB telemetry yields a 32-fold increase in resolution versus standard Nyquist-rate conversion alone, near a four-fold decrease in the volume of uplink data versus single-bit, third-order, delta-sigma modulation, and more than a 20-fold reduction in transmit power versus narrowband transmission for low data rates. The 1.5- mm(2) chip, which was fabricated in 65-nm CMOS technology, consists of a low-noise potentiostat frontend, a two-step analog-to-digital converter (ADC), and an impulse-radio UWB transmitter (TX). The duty-cycled frontend and ADC/UWB-TX blocks draw 4 μA and 15 μA from 3-V and 1.2-V supplies, respectively. The chip achieves an input-referred current noise of 92 pA(rms) and an input current range of ±430 nA at a conversion rate of 10 kHz. The packaged device operates from a 3-V coin-cell battery, measures 4.7 × 1.9 cm(2), weighs 4.3 g (including the battery and antenna), and can be carried by small animals. The system was validated by wirelessly recording flow-injection of dopamine with concentrations in the range of 250 nM to 1 μM with a carbon-fiber microelectrode (CFM) using 300-V/s FSCV.

  6. User-friendly design approach for analog layout design

    NASA Astrophysics Data System (ADS)

    Li, Yongfu; Lee, Zhao Chuan; Tripathi, Vikas; Perez, Valerio; Ong, Yoong Seang; Hui, Chiu Wing

    2017-03-01

    Analog circuits are sensitives to the changes in the layout environment conditions, manufacturing processes, and variations. This paper presents analog verification flow with five types of analogfocused layout constraint checks to assist engineers in identifying any potential device mismatch and layout drawing mistakes. Compared to several solutions, our approach only requires layout design, which is sufficient to recognize all the matched devices. Our approach simplifies the data preparation and allows seamless integration into the layout environment with minimum disruption to the custom layout flow. Our user-friendly analog verification flow provides the engineer with more confident with their layouts quality.

  7. An Experimentation Platform for On-Chip Integration of Analog Neural Networks: A Pathway to Trusted and Robust Analog/RF ICs.

    PubMed

    Maliuk, Dzmitry; Makris, Yiorgos

    2015-08-01

    We discuss the design of an experimentation platform intended for prototyping low-cost analog neural networks for on-chip integration with analog/RF circuits. The objective of such integration is to support various tasks, such as self-test, self-tuning, and trust/aging monitoring, which require classification of analog measurements obtained from on-chip sensors. Particular emphasis is given to cost-efficient implementation reflected in: 1) low energy and area budgets of circuits dedicated to neural networks; 2) robust learning in presence of analog inaccuracies; and 3) long-term retention of learned functionality. Our chip consists of a reconfigurable array of synapses and neurons operating below threshold and featuring sub-μW power consumption. The synapse circuits employ dual-mode weight storage: 1) a dynamic mode, for fast bidirectional weight updates during training and 2) a nonvolatile mode, for permanent storage of learned functionality. We discuss a robust learning strategy, and we evaluate the system performance on several benchmark problems, such as the XOR2-6 and two-spirals classification tasks.

  8. AFEII Analog Front End Board Design Specifications

    SciTech Connect

    Rubinov, Paul; /Fermilab

    2005-04-01

    This document describes the design of the 2nd iteration of the Analog Front End Board (AFEII), which has the function of receiving charge signals from the Central Fiber Tracker (CFT) and providing digital hit pattern and charge amplitude information from those charge signals. This second iteration is intended to address limitations of the current AFE (referred to as AFEI in this document). These limitations become increasingly deleterious to the performance of the Central Fiber Tracker as instantaneous luminosity increases. The limitations are inherent in the design of the key front end chips on the AFEI board (the SVXIIe and the SIFT) and the architecture of the board itself. The key limitations of the AFEI are: (1) SVX saturation; (2) Discriminator to analog readout cross talk; (3) Tick to tick pedestal variation; and (4) Channel to channel pedestal variation. The new version of the AFE board, AFEII, addresses these limitations by use of a new chip, the TriP-t and by architectural changes, while retaining the well understood and desirable features of the AFEI board.

  9. Innovative Teaching of IC Design and Manufacture Using the Superchip Platform

    ERIC Educational Resources Information Center

    Wilson, P. R.; Wilcock, R.; McNally, I.; Swabey, M.

    2010-01-01

    This paper describes how an intelligent chip architecture has allowed a large cohort of undergraduate (UG) students to be given effective practical insight into integrated circuit (IC) design by designing and manufacturing their own ICs. To achieve this, an efficient chip architecture, the "Superchip," was developed, which allows multiple student…

  10. Innovative Teaching of IC Design and Manufacture Using the Superchip Platform

    ERIC Educational Resources Information Center

    Wilson, P. R.; Wilcock, R.; McNally, I.; Swabey, M.

    2010-01-01

    This paper describes how an intelligent chip architecture has allowed a large cohort of undergraduate (UG) students to be given effective practical insight into integrated circuit (IC) design by designing and manufacturing their own ICs. To achieve this, an efficient chip architecture, the "Superchip," was developed, which allows multiple student…

  11. CHARACTERIZATION OF SULFUR CONTAINING ANALOGS OF MONOMETHYLARSONIC ACID IN AQUEOUS PHASE STANDARDS AND CARROT EXTRACTS BY IC-ICP-MS AND IC-ESI-MS/MS

    EPA Science Inventory

    Recently, sulfur analogs of well known arsenicals have been identified, generating a need for stable species-specific standards. This presentation will focus on the identification and characterization of a novel species, monomethylthioarsonic acid (MMTA), in carrots. A standard...

  12. CHARACTERIZATION OF SULFUR CONTAINING ANALOGS OF MONOMETHYLARSONIC ACID IN AQUEOUS PHASE STANDARDS AND CARROT EXTRACTS BY IC-ICP-MS AND IC-ESI-MS/MS

    EPA Science Inventory

    Recently, sulfur analogs of well known arsenicals have been identified, generating a need for stable species-specific standards. This presentation will focus on the identification and characterization of a novel species, monomethylthioarsonic acid (MMTA), in carrots. A standard...

  13. Design and Analysis of Reconfigurable Analog System

    DTIC Science & Technology

    2011-02-01

    34010010" �" �" �" �" �" �" �±" N3 N2 N± P1 P2 P3 * Current sources $RR = 1; *Ramp Rate (slope of the...2008/12/12/31e83bac-500f-4182- acca -4d360295fd9c.pdf, Analog Devices, Analog Dialogue 39-06, June 2005. [15] D. A. Johns, K. Martin "Analog Integrated

  14. Design, synthesis and antibreast cancer MCF-7 cells biological evaluation of heterocyclic analogs of resveratrol.

    PubMed

    Du, Cheng; Dong, Ming-Hui; Ren, Yu-Jie; Jin, Lu; Xu, Cheng

    2017-09-01

    A new series of resveratrol heterocyclic analogs (4a-m) were designed and synthesized, and their inhibitiory effects on MCF-7 cells were evaluated to investigate structure-activity relationship. The effects of these analogs on human breast cancer MCF-7 cells were also determined. Results showed that MCF-7 cells could be inhibited more potently by these analogs than by resveratrol (IC50 = 80.0 μM). Among the analogs, compounds 4c, 4e, and 4k showed a significantly higher activity (IC50 = 42.7, 48.1, and 43.4 μM) than resveratrol. Furthermore, the derivatives without additional heterocyclic structure in the 4'-OH position exhibited a more potent activity than that with addition heterocyclic structure. In addition, docking simulation was performed to adequately position compound 4c in a human F1-ATPase active site to determine a probable binding model. These heterocyclic analogs could be effective candidates for the chemoprevention of human breast cancer.

  15. A quantitative approach to nonlinear IC process design rule scaling

    NASA Astrophysics Data System (ADS)

    Gold, Spencer Montgomery

    As minimum dimensions in integrated circuit technologies are reduced beyond 0.1 m m, linear process scaling becomes more difficult and costly. Exponentially rising manufacturing facility and process scaling costs can be better managed by performing nonlinear process shrinks. Nonlinear scaling allows the horizontal design rules to be reduced by different factors according to their ability to provide area and performance improvement in a cost effective manner. This thesis describes a methodology and CAD tools for use in selecting nonlinear design rule reduction ratios that make effective tradeoffs between die cost and performance. The cost effectiveness of nonlinear scaling is demonstrated for a complementary GaAs (CGaAsTM) process. CGaAs is a young technology with coarse design rules that would benefit significantly from a nonlinear shrink. The cost/benefit analysis for scaling the design rules is based on a process-independent optimizing SRAM compiler which was developed as part of this work. The methodology for nonlinear scaling includes identifying the rules which have the greatest impact on circuit area and analyzing the area and performance improvements as these rules are scaled through a range of practical scale factors. Benefit data (product of power and delay improvement ratios) is then combined with die cost estimates at each step to yield the cost/benefit ratio, a quantitative metric for design rule reduction. The slopes and inflection points of cost/benefit vs. scale factor plots guide process engineers in selecting reduction ratios for the various design rules. This procedure should be repeated, using the results of one pass as the starting point for the next. The cost/benefit analysis methodology compares embedded static RAMs that are generated by the PUMA process-independent SRAM compiler. This compiler, which is based on Duet's MasterPortTM layout compactor, can create optimized SRAM cell libraries for any complementary technology. It is capable of

  16. Design of potent, proteolytically stable oxyntomodulin analogs

    PubMed Central

    Muppidi, Avinash; Zou, Huafei; Yang, Peng Yu; Chao, Elizabeth; Sherwood, Lance; Nunez, Vanessa; Woods, Ashley

    2016-01-01

    Incretin-based peptides are effective therapeutics for treating type 2 diabetes mellitus (T2DM). Oxyntomodulin (OXM), a dual agonist of GLP-1R and GCGR, has shown superior weight loss and glucose lowering effects, compared to single GLP-1R agonists. To overcome the short half-life and rapid renal clearance of OXM, which limit its therapeutic potential, both lipid and PEG modified OXM analogs have been reported. However, these approaches often result in reduced potency or PEG-associated toxicity. Herein we report a new class of cross-linked OXM analogs that show increased plasma stability and higher potency in activating both GLP-1R and GCGR. Moreover, the extended in vivo half-life results in superior anti-hyperglycemic activity in mice compared to the wild-type OXM. PMID:26727558

  17. Biomedical sensor design using analog compressed sensing

    NASA Astrophysics Data System (ADS)

    Balouchestani, Mohammadreza; Krishnan, Sridhar

    2015-05-01

    The main drawback of current healthcare systems is the location-specific nature of the system due to the use of fixed/wired biomedical sensors. Since biomedical sensors are usually driven by a battery, power consumption is the most important factor determining the life of a biomedical sensor. They are also restricted by size, cost, and transmission capacity. Therefore, it is important to reduce the load of sampling by merging the sampling and compression steps to reduce the storage usage, transmission times, and power consumption in order to expand the current healthcare systems to Wireless Healthcare Systems (WHSs). In this work, we present an implementation of a low-power biomedical sensor using analog Compressed Sensing (CS) framework for sparse biomedical signals that addresses both the energy and telemetry bandwidth constraints of wearable and wireless Body-Area Networks (BANs). This architecture enables continuous data acquisition and compression of biomedical signals that are suitable for a variety of diagnostic and treatment purposes. At the transmitter side, an analog-CS framework is applied at the sensing step before Analog to Digital Converter (ADC) in order to generate the compressed version of the input analog bio-signal. At the receiver side, a reconstruction algorithm based on Restricted Isometry Property (RIP) condition is applied in order to reconstruct the original bio-signals form the compressed bio-signals with high probability and enough accuracy. We examine the proposed algorithm with healthy and neuropathy surface Electromyography (sEMG) signals. The proposed algorithm achieves a good level for Average Recognition Rate (ARR) at 93% and reconstruction accuracy at 98.9%. In addition, The proposed architecture reduces total computation time from 32 to 11.5 seconds at sampling-rate=29 % of Nyquist rate, Percentage Residual Difference (PRD)=26 %, Root Mean Squared Error (RMSE)=3 %.

  18. Using Tablet PCs and Interactive Software in IC Design Courses to Improve Learning

    ERIC Educational Resources Information Center

    Simoni, M.

    2011-01-01

    This paper describes an initial study of using tablet PCs and interactive course software in integrated circuit (IC) design courses. A rapidly growing community is demonstrating how this technology can improve learning and retention of material by facilitating interaction between faculty and students via cognitive exercises during lectures. While…

  19. Using Tablet PCs and Interactive Software in IC Design Courses to Improve Learning

    ERIC Educational Resources Information Center

    Simoni, M.

    2011-01-01

    This paper describes an initial study of using tablet PCs and interactive course software in integrated circuit (IC) design courses. A rapidly growing community is demonstrating how this technology can improve learning and retention of material by facilitating interaction between faculty and students via cognitive exercises during lectures. While…

  20. IADE: a system for intelligent automatic design of bioisosteric analogs.

    PubMed

    Ertl, Peter; Lewis, Richard

    2012-11-01

    IADE, a software system supporting molecular modellers through the automatic design of non-classical bioisosteric analogs, scaffold hopping and fragment growing, is presented. The program combines sophisticated cheminformatics functionalities for constructing novel analogs and filtering them based on their drug-likeness and synthetic accessibility using automatic structure-based design capabilities: the best candidates are selected according to their similarity to the template ligand and to their interactions with the protein binding site. IADE works in an iterative manner, improving the fitness of designed molecules in every generation until structures with optimal properties are identified. The program frees molecular modellers from routine, repetitive tasks, allowing them to focus on analysis and evaluation of the automatically designed analogs, considerably enhancing their work efficiency as well as the area of chemical space that can be covered. The performance of IADE is illustrated through a case study of the design of a nonclassical bioisosteric analog of a farnesyltransferase inhibitor--an analog that has won a recent "Design a Molecule" competition.

  1. IADE: a system for intelligent automatic design of bioisosteric analogs

    NASA Astrophysics Data System (ADS)

    Ertl, Peter; Lewis, Richard

    2012-11-01

    IADE, a software system supporting molecular modellers through the automatic design of non-classical bioisosteric analogs, scaffold hopping and fragment growing, is presented. The program combines sophisticated cheminformatics functionalities for constructing novel analogs and filtering them based on their drug-likeness and synthetic accessibility using automatic structure-based design capabilities: the best candidates are selected according to their similarity to the template ligand and to their interactions with the protein binding site. IADE works in an iterative manner, improving the fitness of designed molecules in every generation until structures with optimal properties are identified. The program frees molecular modellers from routine, repetitive tasks, allowing them to focus on analysis and evaluation of the automatically designed analogs, considerably enhancing their work efficiency as well as the area of chemical space that can be covered. The performance of IADE is illustrated through a case study of the design of a nonclassical bioisosteric analog of a farnesyltransferase inhibitor—an analog that has won a recent "Design a Molecule" competition.

  2. Digital I&C systems in nuclear power plants. Risk-screening of environmental stressors and a comparison of hardware unavailability with an existing analog system

    SciTech Connect

    Hassan, M.; Vesely, W.E.

    1998-01-01

    In this report, we present a screening study to identify environmental stressors for digital instrumentation and control (I&C) systems in a nuclear power plant (NPP) which can be potentially risk-significant, and compare the hardware unavailability of such a system with that of its existing analog counterpart. The stressors evaluated are temperature, humidity, vibration, radiation, electro-magnetic interference (EMI), and smoke. The results of risk-screening for an example plant, subject to some bounding assumptions and based on relative changes in plant risk (core damage frequency impacts of the stressors), indicate that humidity, EMI from lightning, and smoke can be potentially risk-significant. Risk from other sources of EMI could not be evaluated for a lack of data. Risk from temperature appears to be insignificant as that from the assumed levels of vibrations. A comparison of the hardware unavailability of the existing analog Safety Injection Actuation System (SIAS) in the example plant with that of an assumed digital upgrade of the system indicates that system unavailability may be more sensitive to the level of redundancy in elements of the digital system than to the environmental and operational variations involved. The findings of this study can be used to focus activities relating to the regulatory basis for digital I&C upgrades in NPPs, including identification of dominant stressors, data-gathering, equipment qualification, and requirements to limit the effects of environmental stressors. 30 refs., 8 figs., 26 tabs.

  3. Design of a Multi-Level/Analog Ferroelectric Memory Device

    NASA Technical Reports Server (NTRS)

    MacLeod, Todd C.; Phillips, Thomas A.; Ho, Fat D.

    2006-01-01

    Increasing the memory density and utilizing the dove1 characteristics of ferroelectric devices is important in making ferroelectric memory devices more desirable to the consumer. This paper describes a design that allows multiple levels to be stored in a ferroelectric based memory cell. It can be used to store multiple bits or analog values in a high speed nonvolatile memory. The design utilizes the hysteresis characteristic of ferroelectric transistors to store an analog value in the memory cell. The design also compensates for the decay of the polarization of the ferroelectric material over time. This is done by utilizing a pair of ferroelectric transistors to store the data. One transistor is used as a reference to determine the amount of decay that has occurred since the pair was programmed. The second transistor stores the analog value as a polarization value between zero and saturated. The design allows digital data to be stored as multiple bits in each memory cell. The number of bits per cell that can be stored will vary with the decay rate of the ferroelectric transistors and the repeatability of polarization between transistors. It is predicted that each memory cell may be able to store 8 bits or more. The design is based on data taken from actual ferroelectric transistors. Although the circuit has not been fabricated, a prototype circuit is now under construction. The design of this circuit is different than multi-level FLASH or silicon transistor circuits. The differences between these types of circuits are described in this paper. This memory design will be useful because it allows higher memory density, compensates for the environmental and ferroelectric aging processes, allows analog values to be directly stored in memory, compensates for the thermal and radiation environments associated with space operations, and relies only on existing technologies.

  4. Design of a Multi-Level/Analog Ferroelectric Memory Device

    NASA Technical Reports Server (NTRS)

    MacLeod, Todd C.; Phillips, Thomas A.; Ho, Fat D.

    2006-01-01

    Increasing the memory density and utilizing the dove1 characteristics of ferroelectric devices is important in making ferroelectric memory devices more desirable to the consumer. This paper describes a design that allows multiple levels to be stored in a ferroelectric based memory cell. It can be used to store multiple bits or analog values in a high speed nonvolatile memory. The design utilizes the hysteresis characteristic of ferroelectric transistors to store an analog value in the memory cell. The design also compensates for the decay of the polarization of the ferroelectric material over time. This is done by utilizing a pair of ferroelectric transistors to store the data. One transistor is used as a reference to determine the amount of decay that has occurred since the pair was programmed. The second transistor stores the analog value as a polarization value between zero and saturated. The design allows digital data to be stored as multiple bits in each memory cell. The number of bits per cell that can be stored will vary with the decay rate of the ferroelectric transistors and the repeatability of polarization between transistors. It is predicted that each memory cell may be able to store 8 bits or more. The design is based on data taken from actual ferroelectric transistors. Although the circuit has not been fabricated, a prototype circuit is now under construction. The design of this circuit is different than multi-level FLASH or silicon transistor circuits. The differences between these types of circuits are described in this paper. This memory design will be useful because it allows higher memory density, compensates for the environmental and ferroelectric aging processes, allows analog values to be directly stored in memory, compensates for the thermal and radiation environments associated with space operations, and relies only on existing technologies.

  5. The design of radiation-hardened ICs for space - A compendium of approaches

    NASA Technical Reports Server (NTRS)

    Kerns, Sherra E.; Shafer, B. D; Rockett, L. R., Jr.; Pridmore, J. S.; Berndt, D. F.

    1988-01-01

    Several technologies, including bulk and epi CMOS, CMOS/SOI-SOS (silicon-on-insulator-silicon-on-sapphire), CML (current-mode logic), ECL (emitter-coupled logic), analog bipolar (JI, single-poly DI, and SOI) and GaAs E/D (enhancement/depletion) heterojunction MESFET, are discussed. The discussion includes the direct effects of space radiation on microelectronic materials and devices, how these effects are evidenced in circuit and device design parameter variations, the particular effects of most significance to each functional class of circuit, specific techniques for hardening high-speed circuits, design examples for integrated systems, including operational amplifiers and A/D (analog/digital) converters, and the computer simulation of radiation effects on microelectronic ISs.

  6. The design of radiation-hardened ICs for space - A compendium of approaches

    NASA Technical Reports Server (NTRS)

    Kerns, Sherra E.; Shafer, B. D; Rockett, L. R., Jr.; Pridmore, J. S.; Berndt, D. F.

    1988-01-01

    Several technologies, including bulk and epi CMOS, CMOS/SOI-SOS (silicon-on-insulator-silicon-on-sapphire), CML (current-mode logic), ECL (emitter-coupled logic), analog bipolar (JI, single-poly DI, and SOI) and GaAs E/D (enhancement/depletion) heterojunction MESFET, are discussed. The discussion includes the direct effects of space radiation on microelectronic materials and devices, how these effects are evidenced in circuit and device design parameter variations, the particular effects of most significance to each functional class of circuit, specific techniques for hardening high-speed circuits, design examples for integrated systems, including operational amplifiers and A/D (analog/digital) converters, and the computer simulation of radiation effects on microelectronic ISs.

  7. Design, synthesis, acetylcholinesterase inhibition and larvicidal activity of girgensohnine analogs on Aedes aegypti, vector of dengue fever.

    PubMed

    Carreño Otero, Aurora L; Vargas Méndez, Leonor Y; Duque L, Jonny E; Kouznetsov, Vladimir V

    2014-05-06

    Girgensohnine alkaloid was used as a natural model in the design and generation of new alkaloid-like α-aminonitrile series that was completed by the use of SSA-catalyzed Strecker reaction between commercial and inexpensive substituted benzaldehydes, piperidine (pyrrolidine, morpholine and N-methylpiperazine) and acetone cyanohydrin. Calculated ADMETox parameters of the designed analogs revealed their good pharmacokinetic profiles indicating lipophilic characteristics. In vitro AChE enzyme test showed that obtained α-aminonitriles could be considered as AChEIs with micromolar IC50 values ranging from 42.0 to 478.0 μM (10.3-124.0 μg/mL). Among this series, the best AChE inhibitor was the pyrrolidine α-aminonitrile 3 (IC50 = 42 μM), followed by the piperidine α-aminonitriles 2 and 6 (IC50 = 45 μM and IC50 = 51 μM, respectively), and the compound 7 (IC50 = 51 μM). In vivo insecticidal activity of more active AChEIs against Aedes aegypti larvae was also performed showing a good larvicidal activity at concentrations less than 140 ppm, highlighting products 2 and 7 that could serve as lead compounds to develop new potent and selective insecticides. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  8. Analogical Reasoning in the Engineering Design Process and Technology Education Applications

    ERIC Educational Resources Information Center

    Daugherty, Jenny; Mentzer, Nathan

    2008-01-01

    This synthesis paper discusses the research exploring analogical reasoning, the role of analogies in the engineering design process, and educational applications for analogical reasoning. Researchers have discovered that analogical reasoning is often a fundamental cognitive tool in design problem solving. Regarding the possible role of analogical…

  9. Analog Design for Digital Deployment of a Serious Leadership Game

    NASA Technical Reports Server (NTRS)

    Maxwell, Nicholas; Lang, Tristan; Herman, Jeffrey L.; Phares, Richard

    2012-01-01

    This paper presents the design, development, and user testing of a leadership development simulation. The authors share lessons learned from using a design process for a board game to allow for quick and inexpensive revision cycles during the development of a serious leadership development game. The goal of this leadership simulation is to accelerate the development of leadership capacity in high-potential mid-level managers (GS-15 level) in a federal government agency. Simulation design included a mixed-method needs analysis, using both quantitative and qualitative approaches to determine organizational leadership needs. Eight design iterations were conducted, including three user testing phases. Three re-design iterations followed initial development, enabling game testing as part of comprehensive instructional events. Subsequent design, development and testing processes targeted digital application to a computer- and tablet-based environment. Recommendations include pros and cons of development and learner testing of an initial analog simulation prior to full digital simulation development.

  10. Design and evaluation of novel interferon lambda analogs with enhanced antiviral activity and improved drug attributes

    PubMed Central

    Yu, Debin; Zhao, Mingzhi; Dong, Liwei; Zhao, Lu; Zou, Mingwei; Sun, Hetong; Zhang, Mengying; Liu, Hongyu; Zou, Zhihua

    2016-01-01

    Type III interferons (IFNs) (also called IFN-λ: IFN-λ1, IFN-λ2, IFN-λ3, and IFN-λ4) are critical players in the defense against viral infection of mucosal epithelial cells, where the activity of type I IFNs is weak, and unlike type I IFNs that are associated with severe and diverse side effects, type III IFNs cause minimal side effects due to the highly restricted expression of their receptors, and thus appear to be promising agents for the treatment and prevention of respiratory and gastrointestinal viral infection. However, the antiviral potency of natural type III IFNs is weak compared to type I and, although IFN-λ3 possesses the highest bioactivity among the type III IFNs, IFN-λ1, instead of IFN-λ3, is being developed as a therapeutic drug due to the difficulty to express IFN-λ3 in the prokaryotic expression system. Here, to develop optimal IFN-λ molecules with improved drug attributes, we designed a series of IFN-λ analogs by replacing critical amino acids of IFN-λ1 with the IFN-λ3 counterparts, and vice versa. Four of the designed analogs were successfully expressed in Escherichia coli with high yield and were easily purified from inclusion bodies. Interestingly, all four analogs showed potent activity in inducing the expression of the antiviral genes MxA and OAS and two of them, analog-6 and -7, displayed an unexpected high potency that is higher than that of type I IFN (IFN-α2a) in activating the IFN-stimulated response element (ISRE)-luciferase reporter. Importantly, both analog-6 and -7 effectively inhibited replication of hepatitis C virus in Huh-7.5.1 cells, with an IC50 that is comparable to that of IFN-α2a; and consistent with the roles of IFN-λ in mucosal epithelia, both analogs potently inhibited replication of H3N2 influenza A virus in A549 cells. Together, these studies identified two IFN-λ analogs as candidates to be developed as novel antiviral biologics. PMID:26792983

  11. Design of an Active Ultrastable Single-chain Insulin Analog

    PubMed Central

    Hua, Qing-xin; Nakagawa, Satoe H.; Jia, Wenhua; Huang, Kun; Phillips, Nelson B.; Hu, Shi-quan; Weiss, Michael A.

    2008-01-01

    Single-chain insulin (SCI) analogs provide insight into the inter-relation of hormone structure, function, and dynamics. Although compatible with wild-type structure, short connecting segments (<3 residues) prevent induced fit upon receptor binding and so are essentially without biological activity. Substantial but incomplete activity can be regained with increasing linker length. Here, we describe the design, structure, and function of a single-chain insulin analog (SCI-57) containing a 6-residue linker (GGGPRR). Native receptor-binding affinity (130 ± 8% relative to the wild type) is achieved as hindrance by the linker is offset by favorable substitutions in the insulin moiety. The thermodynamic stability of SCI-57 is markedly increased (ΔΔGu = 0.7 ± 0.1 kcal/mol relative to the corresponding two-chain analog and 1.9 ± 0.1 kcal/mol relative to wild-type insulin). Analysis of inter-residue nuclear Overhauser effects demonstrates that a native-like fold is maintained in solution. Surprisingly, the glycine-rich connecting segment folds against the insulin moiety: its central Pro contacts ValA3 at the edge of the hydrophobic core, whereas the final Arg extends the A1-A8 α-helix. Comparison between SCI-57 and its parent two-chain analog reveals striking enhancement of multiple native-like nuclear Overhauser effects within the tethered protein. These contacts are consistent with wild-type crystal structures but are ordinarily attenuated in NMR spectra of two-chain analogs, presumably due to conformational fluctuations. Linker-specific damping of fluctuations provides evidence for the intrinsic flexibility of an insulin monomer. In addition to their biophysical interest, ultrastable SCIs may enhance the safety and efficacy of insulin replacement therapy in the developing world. PMID:18332129

  12. Design and Performance of Coherent Analog Optical Links

    NASA Astrophysics Data System (ADS)

    Sabido, Delfin Jay Medel, Ix.

    At present, most of the work on analog optical communication links focused on direct detection techniques. Very little attention has been paid to coherent detection where at the receiving end, a local oscillator laser is used and its output is combined with the incoming optical signal before detection. Coherent detection provides several advantages over conventional direct detection techniques including improved receiver sensitivity, inherent frequency translation, and the ability to utilize angle modulation and separate dense WDM signals. Coherent optical links provide all these advantages at low optical powers which makes them less sensitive to various fiber nonlinear effects. However, coherent optical links are potentially susceptible to the effects of phase noise associated with wide laser linewidths. The work presented in this dissertation is the first attempt at a comprehensive study of a coherent analog optical link, from the design stage, its implementation, characterization and investigations into improving its performance. In this work, an experimental coherent analog optical link was constructed, and theoretical and experimental studies were conducted on the performance of coherent analog optical links as compared to conventional direct detection links. The results of these investigations show that the coherent AM-WIRNA heterodyne link can be made insensitive to laser linewidth for linewidths up to 300 MHz. To the author's best knowledge, this is the first ever demonstration of a gigahertz bandwidth linewidth-insensitive coherent analog optical link. This study indicates that the coherent AM link has a higher spurious-free dynamic range (SFDR), by up to 10 dB, than the corresponding direct detection link, when the received optical power is less than 85 muW, and for link losses greater than 7 dB. However, coherent links were found to be more susceptible to the effects of laser RIN, requiring lasers with RIN better than -140 dB/Hz. In addition, coherent

  13. MagIC: a textile system for vital signs monitoring. Advancement in design and embedded intelligence for daily life applications.

    PubMed

    Di Rienzo, Marco; Rizzo, Francesco; Meriggi, Paolo; Castiglioni, Paolo; Mazzoleni, Paolo; Ferrarin, Maurizio; Ferratini, Maurizio

    2007-01-01

    We recently developed a textile-based system for the unobtrusive assessment of vital signs. The system, named MagIC, was originally designed to collect data in elderly people and cardiac patients while living in a confined environment. Extending the area of application of MagIC from clinics to daily life meant to pay particular attention to the garment design and to the amount of intelligence embedded into the system. In this paper we addressed both these issues by illustrating 1) a new methodology we are developing to help the design of smart garments for daily life applications and 2) an example of embedded intelligence developed for an application of MagIC in ergonomics.

  14. Analysis of flow field characteristics in IC equipment chamber based on orthogonal design

    NASA Astrophysics Data System (ADS)

    Liu, W. F.; Yang, Y. Y.; Wang, C. N.

    2017-01-01

    This paper aims to study the influence of the configuration of processing chamber as a part of IC equipment on flow field characteristics. Four parameters, including chamber height, chamber diameter, inlet mass flow rate and outlet area, are arranged using orthogonally design method to study their influence on flow distribution in the processing chamber with the commercial software-Fluent. The velocity, pressure and temperature distribution above the holder were analysed respectively. The velocity difference value of the gas flow above the holder is defined as the evaluation criteria to evaluate the uniformity of the gas flow. The quantitative relationship between key parameters and the uniformity of gas flow was found through analysis of experimental results. According to our study, the chamber height is the most significant factor, and then follows the outlet area, chamber diameter and inlet mass flow rate. This research can provide insights into the study and design of configuration of etcher, plasma enhanced chemical vapor deposition (PECVD) equipment, and other systems with similar configuration and processing condition.

  15. Planar CMOS analog SiPMs: design, modeling, and characterization

    NASA Astrophysics Data System (ADS)

    Zou, Yu; Villa, Federica; Bronzi, Danilo; Tisa, Simone; Tosi, Alberto; Zappa, Franco

    2015-11-01

    Silicon photomultipliers (SiPMs) are large area detectors consisting of an array of single-photon-sensitive microcells, which make SiPMs extremely attractive to substitute the photomultiplier tubes in many applications. We present the design, fabrication, and characterization of analog SiPMs in standard planar 0.35 μm CMOS technology, with about 1 mm × 1 mm total area and different kinds of microcells, based on single-photon avalanche diodes with 30 μm diameter reaching 21.0% fill-factor (FF), 50 μm diameter (FF = 58.3%) or 50 μm square active area with rounded corner of 5 μm radius (FF = 73.7%). We also developed the electrical SPICE model for CMOS SiPMs. Our CMOS SiPMs have 25 V breakdown voltage, in line with most commercial SiPMs and higher gain (8.8 × 106, 13.2 × 106, and 15.0 × 106, respectively). Although dark count rate density is slightly higher than state-of-the-art analog SiPMs, the proposed standard CMOS processing opens the feasibility of integration with active electronics, for switching hot pixels off, drastically reducing the overall dark count rate, or for further on-chip processing.

  16. Circuit Design Approaches for Implementation of a Subtrellis IC for a Reed-Muller Subcode

    NASA Technical Reports Server (NTRS)

    Lin, Shu; Uehara, Gregory T.; Nakamura, Eric B.; Chu, Cecilia W. P.

    1996-01-01

    In his research, we have proposed the (64, 40, 8) subcode of the third-order Reed-Muller (RM) code to NASA for high-speed satellite communications. This RM subcode can be used either alone or as an inner code of a concatenated coding system with the NASA standard (255, 233, 33) Reed-Solomon (RS) code as the outer code to achieve high performance (or low bit-error rate) with reduced decoding complexity. It can also be used as a component code in a multilevel bandwidth efficient coded modulation system to achieve reliable bandwidth efficient data transmission. This report will summarize the key progress we have made toward achieving our eventual goal of implementing a decoder system based upon this code. In the first phase of study, we investigated the complexities of various sectionalized trellis diagrams for the proposed (64, 40, 8) RM subcode. We found a specific 8-trellis diagram for this code which requires the least decoding complexity with a high possibility of achieving a decoding speed of 600 M bits per second(Mbps). The combination of a large number of states and a high data rate will be made possible due to the utilization of a high degree of parallelism throughout the architecture. This trellis diagram will be presented and briefly described. In the second phase of study which was carried out through the past year, we investigated circuit architectures to determine the feasibility of VLSI implementation of a high- speed Viterbi decoder based on this 8-section trellis diagram. We began to examine specific design and implementation approaches to implement a fully custom integrated circuit (IC) which will be a key building block for a decoder system implementation. The key results will be presented in this report. This report will be divided into three primary sections. First, we will briefly describe the system block diagram in which the proposed decoder is assumed to be operating and present some of the key architectural approaches being used to implement

  17. Circuit Design Approaches for Implementation of a Subtrellis IC for a Reed-Muller Subcode

    NASA Technical Reports Server (NTRS)

    Lin, Shu; Uehara, Gregory T.; Nakamura, Eric B.; Chu, Cecilia W. P.

    1996-01-01

    In this research, we have proposed the (64, 40, 8) subcode of the third-order Reed-Muller (RM) code to NASA for high-speed satellite communications. This RM subcode can be used either alone or as an inner code of a concatenated coding system with the NASA standard (255, 233, 33) Reed-Solomon (RS) code as the outer code to achieve high performance (or low bit-error rate) with reduced decoding complexity. It can also be used as a component code in a multilevel bandwidth efficient coded modulation system to achieve reliable bandwidth efficient data transmission. This report will summarize the key progress we have made toward achieving our eventual goal of implementing a decoder system based upon this code. In the first phase of study, we investigated the complexities of various sectionalized trellis diagrams for the proposed (64, 40, 8) RM subcode. We found a specific 8-trellis diagram for this code which requires the least decoding complexity with a high possibility of achieving a decoding speed of 600 M bits per second (Mbps). The combination of a large number of states and a high data rate will be made possible due to the utilization of a high degree of parallelism throughout the architecture. This trellis diagram will be presented and briefly described. In the second phase of study which was carried out through the past year, we investigated circuit architectures to determine the feasibility of VLSI implementation of a high-speed Viterbi decoder based on this 8-section trellis diagram. We began to examine specific design and implementation approaches to implement a fully custom integrated circuit (IC) which will be a key building block for a decoder system implementation. The key results will be presented in this report. This report will be divided into three primary sections. First, we will briefly describe the system block diagram in which the proposed decoder is assumed to be operating and present some of the key architectural approaches being used to implement

  18. Electrical Characterization of 4H-SiC JFET Wafer: DC Parameter Variations for Extreme Temperature IC Design

    NASA Technical Reports Server (NTRS)

    Neudeck, Philip G.; Chen, Liangyu; Spry, David J.; Beheim, Glenn M.; Chang, Carl W.

    2014-01-01

    This work reports DC electrical characterization of a 76 mm diameter 4H-SiC JFET test wafer fabricated as part of NASA's on-going efforts to realize medium-scale ICs with prolonged and stable circuit operation at temperatures as high as 500 degC. In particular, these measurements provide quantitative parameter ranges for use in JFET IC design and simulation. Larger than expected parameter variations were observed both as a function of position across the wafer as well as a function of ambient testing temperature from 23 degC to 500 degC.

  19. Digital I&C Systems in Nuclear Power Plants. Risk-Screening of Environmental Stressors and a Comparison of Hardware Unavailability With an Existing Analog System

    DTIC Science & Technology

    1998-01-01

    NUREG /CR-6579 BNL- NUREG -52536 Digital I&C Systems in Nuclear Power Plants Risk-Screening of Environmental Stressors and a Comparison of Hardware...13.2.3 NUREG /CR-6579 BNL- NUREG -52536 Digital I&C Systems in Nuclear Power Plants Risk-Screening of Environmental Stressors and a Comparison of...licensee documents and correspondence. The following documents in the NUREG series are available for purchase from the Government Printing Office: formal

  20. Optimization of complex high-dimensional layout configurations for IC physical designs using graph search, data analytics, and machine learning

    NASA Astrophysics Data System (ADS)

    Dai, Vito; Teoh, Edward Kah Ching; Xu, Ji; Rangarajan, Bharath

    2017-04-01

    A typical new IC design has millions of layout configurations, not seen on previous product or test chip designs. Knowing the disposition of each and every configuration, problematic or not, is the key to optimizing design for yield. In this paper, we present a method to systematically characterize the configuration coverage of any layout. Coverage can be compared between designs, and configurations for which there is a lack of coverage can also be computed. When combined with simulation, metrology, and defect data for some configurations, graph search and machine learning algorithms can be applied to optimize designs for manufacturing yield.

  1. Design and Functional Characterization of a Novel Abscisic Acid Analog

    PubMed Central

    Han, Xiaoqiang; Jiang, Lun; Che, Chuanliang; Wan, Chuan; Lu, Huizhe; Xiao, Yumei; Xu, Yanjun; Chen, Zhongzhou; Qin, Zhaohai

    2017-01-01

    The phytohormone abscisic acid (ABA) plays a crucial role in mediating plant growth and development by recruiting genetically redundant ABA receptors. To overcome its oxidation inactivation, we developed a novel ABA analog named 2′,3′-benzo-iso-ABA (iso-PhABA) and studied its function and structural characterization with A. thaliana ABA receptors. The (+)-iso-PhABA form showed much higher ABA-like activities than (+)-ABA including inhibitory effects on the seed germination of lettuce and A. thaliana, wheat embryo germination and rice seedling elongation. The PP2C (protein phosphatases 2C) activity assay showed that (+)-iso-PhABA acted as a potent and selective ABA receptor agonist, which is preferred to PYL10. In some cases, (−)-iso-PhABA showed moderate to high activity for the PYL protein inhibiting PP2C activity, suggesting different mechanisms of action of iso-PhABA and ABA. The complex crystal structure of iso-PhABA with PYL10 was determined and elucidated successfully, revealing that (+)-iso-PhABA was better coordinated in the same binding pocket compared to (+)-ABA. Moreover, the detailed interaction network of iso-PhABA/PYL10 was disclosed and involves hydrogen bonds and multiple hydrophobic interactions that provide a robust framework for the design of novel ABA receptor agonists/antagonists. PMID:28272449

  2. Design and Functional Characterization of a Novel Abscisic Acid Analog.

    PubMed

    Han, Xiaoqiang; Jiang, Lun; Che, Chuanliang; Wan, Chuan; Lu, Huizhe; Xiao, Yumei; Xu, Yanjun; Chen, Zhongzhou; Qin, Zhaohai

    2017-03-08

    The phytohormone abscisic acid (ABA) plays a crucial role in mediating plant growth and development by recruiting genetically redundant ABA receptors. To overcome its oxidation inactivation, we developed a novel ABA analog named 2',3'-benzo-iso-ABA (iso-PhABA) and studied its function and structural characterization with A. thaliana ABA receptors. The (+)-iso-PhABA form showed much higher ABA-like activities than (+)-ABA including inhibitory effects on the seed germination of lettuce and A. thaliana, wheat embryo germination and rice seedling elongation. The PP2C (protein phosphatases 2C) activity assay showed that (+)-iso-PhABA acted as a potent and selective ABA receptor agonist, which is preferred to PYL10. In some cases, (-)-iso-PhABA showed moderate to high activity for the PYL protein inhibiting PP2C activity, suggesting different mechanisms of action of iso-PhABA and ABA. The complex crystal structure of iso-PhABA with PYL10 was determined and elucidated successfully, revealing that (+)-iso-PhABA was better coordinated in the same binding pocket compared to (+)-ABA. Moreover, the detailed interaction network of iso-PhABA/PYL10 was disclosed and involves hydrogen bonds and multiple hydrophobic interactions that provide a robust framework for the design of novel ABA receptor agonists/antagonists.

  3. Wideband Analog Data System (WADS), system design document

    NASA Technical Reports Server (NTRS)

    Brose, J. F.

    1979-01-01

    The Wideband Analog System (WADS) which performs post flight structural dynamic analysis of wideband FM data recorded during orbital flight tests is defined. Screening, reporting, and plotting steady state and transient wave analysis data are provided by WADS.

  4. Lunar Analog

    NASA Technical Reports Server (NTRS)

    Cromwell, Ronita L.

    2009-01-01

    In this viewgraph presentation, a ground-based lunar analog is developed for the return of manned space flight to the Moon. The contents include: 1) Digital Astronaut; 2) Bed Design; 3) Lunar Analog Feasibility Study; 4) Preliminary Data; 5) Pre-pilot Study; 6) Selection of Stockings; 7) Lunar Analog Pilot Study; 8) Bed Design for Lunar Analog Pilot.

  5. Comparison of various spring analogy related mesh deformation techniques in two-dimensional airfoil design optimization

    NASA Astrophysics Data System (ADS)

    Yang, Y.; Özgen, S.

    2017-06-01

    During the last few decades, CFD (Computational Fluid Dynamics) has developed greatly and has become a more reliable tool for the conceptual phase of aircraft design. This tool is generally combined with an optimization algorithm. In the optimization phase, the need for regenerating the computational mesh might become cumbersome, especially when the number of design parameters is high. For this reason, several mesh generation and deformation techniques have been developed in the past decades. One of the most widely used techniques is the Spring Analogy. There are numerous spring analogy related techniques reported in the literature: linear spring analogy, torsional spring analogy, semitorsional spring analogy, and ball vertex spring analogy. This paper gives the explanation of linear spring analogy method and angle inclusion in the spring analogy method. In the latter case, two di¨erent solution methods are proposed. The best feasible method will later be used for two-dimensional (2D) Airfoil Design Optimization with objective function being to minimize sectional drag for a required lift coe©cient at di¨erent speeds. Design variables used in the optimization include camber and thickness distribution of the airfoil. SU2 CFD is chosen as the §ow solver during the optimization procedure. The optimization is done by using Phoenix ModelCenter Optimization Tool.

  6. Design of A 5-Bit Fully Parallel Analog to Digital Converter Using Common Gate Differrential Mos Pair-Based Comparator

    NASA Astrophysics Data System (ADS)

    Aytar, Oktay

    2015-09-01

    This paper presents a novel comparator structure based on the common gate differential MOS pair. The proposed comparator has been applied to fully parallel analog to digital converter (A/D converter). Furthermore, this article presents 5 bit fully parallel A/D Converter design using the cadence IC5141 design platform and NCSU(North Carolina State University) design kit with 0.18 μm CMOS technology library. The proposed fully parallel A/D converter consist of resistor array block, comparator block, 1-n decoder block and programmable logic array. The 1-n decoder block includes latch block and thermometer code circuit that is implemented using transmission gate based multiplexer circuit. Thus, sampling frequency and analog bandwidth are increased. The INL and DNL of the proposed fully parallel A/D converter are (0/ + 0.63) LSB and (-0.26/ + 0.31) LSB at a sampling frequency of 5 GS/s with an input signal of 50 MHz, respectively. The proposed fully parallel A/D Converter consumes 340 mW from 1.8 V supply.

  7. FPGA Design Practices for I&C in Nuclear Power Plants

    SciTech Connect

    Bobrek, Miljko; Wood, Richard Thomas; Bouldin, Donald; Waterman, Michael E

    2009-01-01

    Safe FPGA design practices can be classified into three major groups covering board-level and FPGA logic-level design practices, FPGA design entry methods, and FPGA design methodology. This paper is presenting the most common hardware and software design practices that are acceptable in safety-critical FPGA systems. It also proposes an FPGA-specific design life cycle including design entry, FPGA synthesis, place and route, and validation and verification.

  8. 3D Integration of MEMS and IC: Design, Technology and Simulations

    NASA Astrophysics Data System (ADS)

    Taklo, Maaike M. V.; Schjølberg-Henriksen, Kari; Lietaer, Nicolas; Prainsack, Josef; Elfving, Anders; Weber, Josef; Klein, Matthias; Schneider, Peter; Reitz, Sven

    A 3D integrated silicon stack consisting of two MEMS devices and two IC devices is presented. The MEMS devices are a pressure sensor and a bulk acoustic resonator (BAR). The stack was constructed for a tire pressure monitoring system (TPMS) which was one out of three demonstrators for an EU funded project called e-CUBES. Thermal simulations were performed to check the level of thermo-mechanical stresses induced on the pressure sensor membrane during extreme environmental conditions. Additional simulations were made to calculate the exact temperature on the BAR device during operation as this was important for the operational frequency. This paper presents and discusses the technology choices made for the stacking of the pressure sensor and the BAR. Results are given from simulations, initial short-loop experiments and for the final stacking.

  9. Optimizing study design for interobserver reliability: IUGA-ICS classification of complications of prostheses and graft insertion.

    PubMed

    Haylen, Bernard T; Lee, Joseph; Maher, Chris; Deprest, Jan; Freeman, Robert

    2014-06-01

    Results of interobserver reliability studies for the International Urogynecological Association-International Continence Society (IUGA-ICS) Complication Classification coding can be greatly influenced by study design factors such as participant instruction, motivation, and test-question clarity. We attempted to optimize these factors. After a 15-min instructional lecture with eight clinical case examples (including images) and with classification/coding charts available, those clinicians attending an IUGA Surgical Complications workshop were presented with eight similar-style test cases over 10 min and asked to code them using the Category, Time and Site classification. Answers were compared to predetermined correct codes obtained by five instigators of the IUGA-ICS prostheses and grafts complications classification. Prelecture and postquiz participant confidence levels using a five-step Likert scale were assessed. Complete sets of answers to the questions (24 codings) were provided by 34 respondents, only three of whom reported prior use of the charts. Average score [n (%)] out of eight, as well as median score (range) for each coding category were: (i) Category: 7.3 (91 %); 7 (4-8); (ii) Time: 7.8 (98 %); 7 (6-8); (iii) Site: 7.2 (90 %); 7 (5-8). Overall, the equivalent calculations (out of 24) were 22.3 (93 %) and 22 (18-24). Mean prelecture confidence was 1.37 (out of 5), rising to 3.85 postquiz. Urogynecologists had the highest correlation with correct coding, followed closely by fellows and general gynecologists. Optimizing training and study design can lead to excellent results for interobserver reliability of the IUGA-ICS Complication Classification coding, with increased participant confidence in complication-coding ability.

  10. Digital-Analog-Hybrid Neural Simulator: A Design-Aid For Custom-VLSI Neurochips

    NASA Astrophysics Data System (ADS)

    Moopenn, Alexander W.; Thakoor, Anilkumar P.; Duong, Tuan A.

    1989-05-01

    A high speed neural network simulator and its use for the dynamics and performance analysis of feedback neural architectures are described. The simulator is based on a semi-parallel, analog-digital hybrid architecture which utilizes digital memories to store synaptic weights and analog hardware for high speed computation. A breadboard system with 8-bit gray scale synapses, designed and built at JPL, is successfully serving as a valuable design test-bed for the development of fully parallel, analog, custom VLSI neurochips, currently underway at JPL. The breadboard hybrid simulator indeed allows a detailed evaluation of hardware potential and limitations in implementing full analog operations in such chips. As an example, the paper presents an analysis of the stability and convergence behavior of a feedback neural network applied to the "Concentrator Assignment Problem" in combinatorial optimization, as studied on the analog-digital hybrid simulator. This has already resulted in a VLSI custom design of a fully parallel, analog neuroprocessor with a powerful "analog prompting" feature, for the high-speed, multiparameter optimization function.

  11. An investigation of fluid flow during induction stroke of a water analog model of an IC engine using an innovative optical velocimetry concept: LIPA

    NASA Technical Reports Server (NTRS)

    Stier, Bernd; Falco, R. E.

    1994-01-01

    Optical measurements on an axisymmetrical quartz component engine research model were made to evaluate the flow field encountered during induction. The measurement technique is LIPA (Laser Induced Photochemical Anemometry), a non-intrusive velocimetry concept that provides an investigator of fluid flow with a tool to attain planar information about three-dimensional velocity and vorticity vectors in a single measurement step. The goal of this investigation is to further develop this measurement technique and apply it to study the induction stroke of a water analog model of a four-stroke internal combustion engine. The research conducted in the water analog model is a fundamental scientific inquiry into the flow fields that develop in the induction stroke of an engine at idling engine speeds. As this is the first investigation of its kind using LIPA technique, our goal has been to quantify, in a preliminary manner, the flow field features that develop during the intake stroke. In the process a more comprehensive understanding of the flow field features was developed, and tied to the quantification. The study evaluated the flow field of the intake stroke by estimating fields of velocity and vorticity. On the basis of these data, information about fluid dynamics during induction at engine speeds of 10, 20, and 30 RPM (corresponding to 170, 340, and 510 RPM respectively, when air is the flowing medium) for three different valve lifts was obtained. The overall development of the flow field, its energy content (kinetic, fluctuation) for the different settings of the engine parameters, vorticity information, and cyclic variations have been quantified. These have been discussed in terms of mixing performance.

  12. Bicomponent electrospun scaffolds to design extracellular matrix tissue analogs.

    PubMed

    Guarino, Vincenzo; Cirillo, Valentina; Ambrosio, Luigi

    2016-01-01

    In the last decade, bicomponent fibers have been proposed to fabricate bio-inspired systems for tissue repair, regenerative medicine, medical healthcare and clinical applications. In comparison with monocomponent fibers, key advantage concerns their ability of self-adapting to the physiological conditions through an extended pattern of signals--morphological, chemical and physical ones--confined at the single fiber level. Hydrophobic/hydrophilic phases may be variously organized by tuneable processing modes (i.e., blending, core/shell, interweaving) thus offering different benefits in terms of biological activity, fluid sorption and molecular transport properties (first generation). The possibility to efficiently graft cell-adhesive proteins and peptide sequences onto the fiber surface mediated by spacers or impregnating hydrogels allows to trigger cell late activities by a controlled and sustained release in vitro of specific biomolecules (i.e., morphogens, growth factors). Here, we introduce an overview of current approaches based on bicomponent fiber use as extra cellular matrix analogs with cell-instructive functions and hierarchal organization of living tissues.

  13. Design, synthesis and molecular docking of α,β-unsaturated cyclohexanone analogous of curcumin as potent EGFR inhibitors with antiproliferative activity.

    PubMed

    Xu, Yun-Yun; Cao, Yi; Ma, Hailkuo; Li, Huan-Qiu; Ao, Gui-Zhen

    2013-01-15

    A type of novel α,β-unsaturated cyclohexanone analogous, which designed based on the curcumin core structure, have been discovered as potential EGFR inhibitors. These compounds exhibit potent antiproliferative activity in two human tumor cell lines (Hep G2 and B16-F10). Among them, compounds I(3) and I(12) displayed the most potent EGFR inhibitory activity (IC(50) = 0.43 μM and 1.54 μM, respectively). Molecular docking of I(12) into EGFR TK active site was also performed. This inhibitor nicely fitting the active site might well explain its excellent inhibitory activity.

  14. Design, Synthesis and Biological Evaluation of Platensimycin Analogs with Varying Degrees of Molecular Complexity

    PubMed Central

    Nicolaou, K. C.; Stepan, Antonia F.; Lister, Troy; Li, Ang; Montero, Ana; Tria, G. Scott; Turner, Craig I.; Tang, Yefeng; Wang, Jianhua; Denton, Ross M.; Edmonds, David J.

    2009-01-01

    The molecular design, chemical synthesis and biological evaluation of two distinct series of platensimycin analogs with varying degrees of complexity are described. The first series of compounds (analog series I: 6, 15–18, Figure 3) probes the biological importance of the benzoic acid subunit of the molecule, whilst the second series (analog series II: 2, 3, 9–14) explores the tetracyclic cage domain. The biological data obtained reveal that while the substituted benzoic acid domain of platensimycin is a highly conserved structural motif within the active compounds with strict functional group requirements, the cage domain of the molecule can tolerate considerable structural modifications without losing biological action. These findings refine our present understanding of the platensimycin pharmacophore and establish certain structure activity relationships (SARs) from which the next generation of designed analogs of this new antibiotic may emerge. PMID:18771264

  15. Architectures and design techniques for real-time image processing ICs

    SciTech Connect

    Ruetz, P.A.

    1986-01-01

    A set of 8 chips, which perform real-time image processing tasks, was designed and fabricated with a 4..mu.. MNOS technology. The chips include: a 3 x 3 linear convolver, a 3 x 3 sorting filter, a 7 x 7 logical convolver, a contour tracer, a feature extractor, a look-up table ROM, and two post processors for the linear convolver. All chips were designed using architectures dedicated to the particular image processing tasks to be performed. The image processing circuits operate on 10-MHz video data (512 x 512 pixel images). The design time for the chips was kept to 1.5 man years by re-using hardware and, in addition, utilizing and developing some appropriate CAD tools. ROM generators and a data-path generator were developed to reduce the circuit design time. An image-recognition system was built with these custom chips that can recognize two dimensional objects that are characterized by their closed outer contours. The complete system is controlled by a SUN work station and operates at rates up to 15 frame/Sec. The recognition system achieved a 97% recognition rate for 8 objects over a wide range of orientation and size variations and a 100% recognition rate without size variations.

  16. Intrinsic Hardware Evolution for the Design and Reconfiguration of Analog Speed Controllers for a DC Motor

    NASA Technical Reports Server (NTRS)

    Gwaltney, David A.; Ferguson, Michael I.

    2003-01-01

    Evolvable hardware provides the capability to evolve analog circuits to produce amplifier and filter functions. Conventional analog controller designs employ these same functions. Analog controllers for the control of the shaft speed of a DC motor are evolved on an evolvable hardware platform utilizing a second generation Field Programmable Transistor Array (FPTA2). The performance of an evolved controller is compared to that of a conventional proportional-integral (PI) controller. It is shown that hardware evolution is able to create a compact design that provides good performance, while using considerably less functional electronic components than the conventional design. Additionally, the use of hardware evolution to provide fault tolerance by reconfiguring the design is explored. Experimental results are presented showing that significant recovery of capability can be made in the face of damaging induced faults.

  17. Intrinsic Hardware Evolution for the Design and Reconfiguration of Analog Speed Controllers for a DC Motor

    NASA Technical Reports Server (NTRS)

    Gwaltney, David A.; Ferguson, Michael I.

    2003-01-01

    Evolvable hardware provides the capability to evolve analog circuits to produce amplifier and filter functions. Conventional analog controller designs employ these same functions. Analog controllers for the control of the shaft speed of a DC motor are evolved on an evolvable hardware platform utilizing a second generation Field Programmable Transistor Array (FPTA2). The performance of an evolved controller is compared to that of a conventional proportional-integral (PI) controller. It is shown that hardware evolution is able to create a compact design that provides good performance, while using considerably less functional electronic components than the conventional design. Additionally, the use of hardware evolution to provide fault tolerance by reconfiguring the design is explored. Experimental results are presented showing that significant recovery of capability can be made in the face of damaging induced faults.

  18. Design, Synthesis and Biological Activities of Novel Gemini 20S-Hydroxyvitamin D3 Analogs

    PubMed Central

    LIN, ZONGTAO; MAREPALLY, SRINIVASA R.; KIM, TAE-KANG; JANJETOVIC, ZORICA; OAK, ALLEN SW.; POSTLETHWAITE, ARNOLD E.; MYERS, LINDA K.; TUCKEY, ROBERT C.; SLOMINSKI, ANDRZEJ T.; MILLER, DUANE D.; LI, WEI

    2017-01-01

    Vitamin D3 (D3) can be metabolized by cytochrome P450scc (CYP11A1) into 20S-hydroxyvitamin D3 (20D3) as a major metabolite. This bioactive metabolite has shown strong antiproliferative, antifibrotic, pro-differentiation and anti-inflammatory effects while being non-toxic (non-calcemic) at high concentrations. Since D3 analogs with two symmetric side chains (Gemini analogs) result in potent activation of the vitamin D receptor (VDR), we hypothesized that the chain length and composition of these types of analogs also containing a 20-hydroxyl group would affect their biological activities. In this study, we designed and synthesized a series of Gemini 20D3 analogs. Biological tests showed that some of these analogs are partial VDR activators and can significantly stimulate the expression of mRNA for VDR and VDR-regulated genes including CYP24A1 and transient receptor potential cation channel V6 (TRPV6). These analogs inhibited the proliferation of melanoma cells with potency comparable to that of 1α,25-dihydroxyvitamin D3. Moreover, these analogs reduced the level of interferon γ and up-regulated the expression of leukocyte associated immunoglobulin-like receptor 1 in splenocytes, indicating that they have potent anti-inflammatory activities. There are no clear correlations between the Gemini chain length and their VDR activation or biological activities, consistent with the high flexibility of the ligand-binding pocket of the VDR. PMID:26976974

  19. Design of a reversible biotin analog and applications in protein labeling, detection, and isolation.

    PubMed

    Ying, Lai-Qiang; Branchaud, Bruce P

    2011-08-14

    To expand the applicability of the biotin-(strept)avidin system, a biotin analog with reversible binding under non-denaturing conditions has been designed, and its applications in protein labeling, detection, and isolation have been evaluated. This journal is © The Royal Society of Chemistry 2011

  20. [Principles of design of neural-network analog-to-digital converters of bioelectric signals].

    PubMed

    Loktiukhin, V N; Chelebaev, S V

    2007-01-01

    A design principle and a procedure for synthesis of neural-network analog-to-digital converters of bioelectric signals are suggested. An example of implementation of an FPGA-based neural-network converter for classification of bioparameters is presented.

  1. The impact of analogies on creative concept generation: lessons from an in vivo study in engineering design.

    PubMed

    Chan, Joel; Schunn, Christian

    2015-01-01

    Research on innovation often highlights analogies from sources outside the current problem domain as a major source of novel concepts; however, the mechanisms underlying this relationship are not well understood. We analyzed the temporal interplay between far analogy use and creative concept generation in a professional design team's brainstorming conversations, investigating the hypothesis that far analogies lead directly to very novel concepts via large steps in conceptual spaces (jumps). Surprisingly, we found that concepts were more similar to their preceding concepts after far analogy use compared to baseline situations (i.e., without far analogy use). Yet far analogies increased the team's concept generation rate compared to baseline conditions. Overall, these results challenge the view that far analogies primarily lead to novel concepts via jumps in conceptual spaces and suggest alternative pathways from far analogies to novel concepts (e.g., iterative, deep exploration within a functional space).

  2. Design and Evaluation of New Analogs of the Sweet Protein Brazzein

    PubMed Central

    Cragin, Tiffany; Jin, Zheyuan; Rumbley, Jon N.; Hellekant, Göran

    2009-01-01

    We have previously modeled the interaction of the sweet protein brazzein with the extracellular domains of the sweet taste receptor. Here, we describe the application of that model to the design of 12 new highly potent analogs of brazzein. Eight of the 12 analogs have higher sweetness potency than wild-type brazzein. Results are consistent with our brazzein–receptor interaction model. The model predicts binding of brazzein to the open form of T1R2 in the T1R2–T1R3 heterodimer. PMID:19696120

  3. Design and evaluation of new analogs of the sweet protein brazzein.

    PubMed

    Walters, D Eric; Cragin, Tiffany; Jin, Zheyuan; Rumbley, Jon N; Hellekant, Göran

    2009-10-01

    We have previously modeled the interaction of the sweet protein brazzein with the extracellular domains of the sweet taste receptor. Here, we describe the application of that model to the design of 12 new highly potent analogs of brazzein. Eight of the 12 analogs have higher sweetness potency than wild-type brazzein. Results are consistent with our brazzein-receptor interaction model. The model predicts binding of brazzein to the open form of T1R2 in the T1R2-T1R3 heterodimer.

  4. Design, synthesis and initial biological evaluation of a novel pladienolide analog scaffold.

    PubMed

    Gundluru, Mahesh Kumar; Pourpak, Alan; Cui, Xiaoli; Morris, Stephan W; Webb, Thomas R

    2011-01-01

    A novel and simplified synthetic scaffold based on pladienolide was designed using a consensus pharmacophore hypothesis. An initial target was synthesized and evaluated to examine the role of the 3-hydroxy group and the methyl groups present at positions 10, 16, 20, 22 in 1, on biological activity. We report the first totally synthetic analog of this macrolide that shows biological activity. Our novel synthetic strategy enables the rapid synthesis of other new analogs of pladienolide in order to develop selective anticancer lead compounds.

  5. Design, Synthesis, Activity and Docking Study of Sorafenib Analogs Bearing Sulfonylurea Unit.

    PubMed

    Wu, Chunjiang; Wang, Min; Tang, Qidong; Luo, Rong; Chen, Le; Zheng, Pengwu; Zhu, Wufu

    2015-10-23

    Two series of novel sorafenib analogs containing a sulfonylurea unit were synthesized and their chemical structures were confirmed by ¹H-NMR, ¹³C-NMR, MS spectrum and elemental analysis. The synthesized compounds were evaluated for the cytotoxicity against A549, Hela, MCF-7, and PC-3 cancer cell lines. Some of the compounds showed moderate cytotoxic activity, especially compounds 1-(2,4-difluorophenylsulfonyl)-3-(4-(2-(methylcarbamoyl)pyridin-4-yloxy)phenyl)urea (6c) and 1-(4-bromophenylsulfonyl)-3-(4-(2-(methylcarbamoyl)pyridin-4-yloxy)phenyl)urea (6f) with the IC50 values against four cancer cell lines ranging from 16.54±1.22 to 63.92±1.81 μM, respectively. Inhibitory rates against vascular endothelial growth factor receptor-2 (VEGFR2/KDR) kinase at 10 μM of target compounds were further carried out in this paper in order to investigate the target of these compounds. Structure-activity relationships (SARs) and docking studies indicated that the sulfonylurea unit was important to these kinds of compounds. None of the substitutions in the phenoxy group and small halogen atoms such as 2,4-difluoro substitution of the aryl group contributed to the activity. The results suggested that sulfonylurea sorafenib analogs are worthy of further study.

  6. Design, Synthesis and Biological Activities of Novel Gemini 20S-Hydroxyvitamin D3 Analogs.

    PubMed

    Lin, Zongtao; Marepally, Srinivasa R; Kim, Tae-Kang; Janjetovic, Zorica; Oak, Allen Sw; Postlethwaite, Arnold E; Myers, Linda K; Tuckey, Robert C; Slominski, Andrzej T; Miller, Duane D; Li, Wei

    2016-03-01

    Vitamin D3 (D3) can be metabolized by cytochrome P450scc (CYP11A1) into 20S-hydroxyvitamin D3 (20D3) as a major metabolite. This bioactive metabolite has shown strong antiproliferative, antifibrotic, pro-differentiation and anti-inflammatory effects while being non-toxic (non-calcemic) at high concentrations. Since D3 analogs with two symmetric side chains (Gemini analogs) result in potent activation of the vitamin D receptor (VDR), we hypothesized that the chain length and composition of these types of analogs also containing a 20-hydroxyl group would affect their biological activities. In this study, we designed and synthesized a series of Gemini 20D3 analogs. Biological tests showed that some of these analogs are partial VDR activators and can significantly stimulate the expression of mRNA for VDR and VDR-regulated genes including CYP24A1 and transient receptor potential cation channel V6 (TRPV6). These analogs inhibited the proliferation of melanoma cells with potency comparable to that of 1α,25-dihydroxyvitamin D3. Moreover, these analogs reduced the level of interferon γ and up-regulated the expression of leukocyte associated immunoglobulin-like receptor 1 in splenocytes, indicating that they have potent anti-inflammatory activities. There are no clear correlations between the Gemini chain length and their VDR activation or biological activities, consistent with the high flexibility of the ligand-binding pocket of the VDR. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  7. In silico design and screening of hypothetical MOF-74 analogs and their experimental synthesis

    DOE PAGES

    Witman, Matthew; Ling, Sanliang; Anderson, Samantha; ...

    2016-06-21

    Here, we present the in silico design of metal-organic frameworks (MOFs) exhibiting 1-dimensional rod topologies. We then introduce an algorithm for construction of this family of MOF topologies, and illustrate its application for enumerating MOF-74-type analogs. Furthermore, we perform a broad search for new linkers that satisfy the topological requirements of MOF-74 and consider the largest database of known chemical space for organic compounds, the PubChem database. Our in silico crystal assembly, when combined with dispersion-corrected density functional theory (DFT) calculations, is demonstrated to generate a hypothetical library of open-metal site containing MOF-74 analogs in the 1-D rod topology frommore » which we can simulate the adsorption behavior of CO 2 . We conclude that these hypothetical structures have synthesizable potential through computational identification and experimental validation of a novel MOF-74 analog, Mg 2 (olsalazine).« less

  8. In silico design and screening of hypothetical MOF-74 analogs and their experimental synthesis

    SciTech Connect

    Witman, Matthew; Ling, Sanliang; Anderson, Samantha; Tong, Lianheng; Stylianou, Kyriakos C.; Slater, Ben; Smit, Berend; Haranczyk, Maciej

    2016-06-21

    Here, we present the in silico design of metal-organic frameworks (MOFs) exhibiting 1-dimensional rod topologies. We then introduce an algorithm for construction of this family of MOF topologies, and illustrate its application for enumerating MOF-74-type analogs. Furthermore, we perform a broad search for new linkers that satisfy the topological requirements of MOF-74 and consider the largest database of known chemical space for organic compounds, the PubChem database. Our in silico crystal assembly, when combined with dispersion-corrected density functional theory (DFT) calculations, is demonstrated to generate a hypothetical library of open-metal site containing MOF-74 analogs in the 1-D rod topology from which we can simulate the adsorption behavior of CO 2 . We conclude that these hypothetical structures have synthesizable potential through computational identification and experimental validation of a novel MOF-74 analog, Mg 2 (olsalazine).

  9. Design of a fiber-optic transmitter for microwave analog transmission with high phase stability

    NASA Technical Reports Server (NTRS)

    Logan, R. T., Jr.; Lutes, G. F.; Primas, L. E.; Maleki, L.

    1990-01-01

    The principal considerations in the design of fiber-optic transmitters for highly phase-stable radio frequency and microwave analog transmission are discussed. Criteria for a fiber-optic transmitter design with improved amplitude and phase-noise performance are developed through consideration of factors affecting the phase noise, including low-frequency laser-bias supply noise, the magnitude and proximity of external reflections into the laser, and temperature excursions of the laser-transmitter package.

  10. Design, synthesis, and evaluation of potent bryostatin analogs that modulate PKC translocation selectivity.

    PubMed

    Wender, Paul A; Baryza, Jeremy L; Brenner, Stacey E; DeChristopher, Brian A; Loy, Brian A; Schrier, Adam J; Verma, Vishal A

    2011-04-26

    Modern methods for the identification of therapeutic leads include chemical or virtual screening of compound libraries. Nature's library represents a vast and diverse source of leads, often exhibiting exquisite biological activities. However, the advancement of natural product leads into the clinic is often impeded by their scarcity, complexity, and nonoptimal properties or efficacy as well as the challenges associated with their synthesis or modification. Function-oriented synthesis represents a strategy to address these issues through the design of simpler and therefore synthetically more accessible analogs that incorporate the activity-determining features of the natural product leads. This study illustrates the application of this strategy to the design and synthesis of functional analogs of the bryostatin marine natural products. It is specifically directed at exploring the activity-determining role of bryostatin A-ring functionality on PKC affinity and selectivity. The resultant functional analogs, which were prepared by a flexible, modular synthetic strategy, exhibit excellent affinity to PKC and differential isoform selectivity. These and related studies provide the basic information needed for the design of simplified and thus synthetically more accessible functional analogs that target PKC isoforms, major targets of therapeutic interest.

  11. Design, synthesis, and evaluation of potent bryostatin analogs that modulate PKC translocation selectivity

    PubMed Central

    Wender, Paul A.; Baryza, Jeremy L.; Brenner, Stacey E.; DeChristopher, Brian A.; Loy, Brian A.; Schrier, Adam J.; Verma, Vishal A.

    2011-01-01

    Modern methods for the identification of therapeutic leads include chemical or virtual screening of compound libraries. Nature’s library represents a vast and diverse source of leads, often exhibiting exquisite biological activities. However, the advancement of natural product leads into the clinic is often impeded by their scarcity, complexity, and nonoptimal properties or efficacy as well as the challenges associated with their synthesis or modification. Function-oriented synthesis represents a strategy to address these issues through the design of simpler and therefore synthetically more accessible analogs that incorporate the activity-determining features of the natural product leads. This study illustrates the application of this strategy to the design and synthesis of functional analogs of the bryostatin marine natural products. It is specifically directed at exploring the activity-determining role of bryostatin A-ring functionality on PKC affinity and selectivity. The resultant functional analogs, which were prepared by a flexible, modular synthetic strategy, exhibit excellent affinity to PKC and differential isoform selectivity. These and related studies provide the basic information needed for the design of simplified and thus synthetically more accessible functional analogs that target PKC isoforms, major targets of therapeutic interest. PMID:21415363

  12. Design, synthesis, and biological evaluation of chicoric acid analogs as inhibitors of HIV-1 integrase.

    PubMed

    Charvat, Trevor T; Lee, Deborah J; Robinson, W Edward; Chamberlin, A Richard

    2006-07-01

    A series of analogs of the potent HIV-1 integrase (HIV IN) inhibitor chicoric acid (CA) was designed with the intention of ameliorating some of the parent natural product's undesirable properties, in particular its toxicity, instability, and poor membrane permeability. More than 70 analogs were synthesized and assayed for three types of activity: (1) the ability to inhibit 3'-end processing and strand transfer reactions using recombinant HIV IN in vitro, (2) toxicity against the CD4+ lymphoblastoid cell line, MT2, and (3) anti-HIV activity against HIV(LAI). CA analogs lacking one of the carboxyl groups of CA and with 3,4,5-trihydroxycinnamoyl sidechains in place of the caffeoyl group of CA exhibited the most potent inhibition of HIV replication and end-processing activity. Galloyl-substituted derivatives also displayed very potent in vitro and in vivo activities, in most cases exceeding the inhibitory effects of CA itself. Conversely, analogous monocarboxy caffeoyl analogs exhibited only modest inhibition, while the corresponding 3,4-dihydroxybenzoyl-substituted compounds were devoid of activity.

  13. Design, synthesis and 64Cu labeling of fatty acid analogs containing dithiosemicarbazone chelate.

    PubMed

    Arano, Y; Magata, Y; Horiuchi, K; Matsumoto, K; Fujibayashi, Y; Ohmomo, Y; Tanaka, C; Saji, H; Yokoyama, A

    1989-01-01

    For the development of 62Cu labeled fatty acid analogs, two fatty acid analogs, containing dithiosemicarbazone (DTS) molecule as the 62Cu coordinating site, were designed and synthesized: a fatty acid analog containing DTS molecule at the omega-position, (a) the 12,13-dioxotetradecanoic acid di(N-methyl-thiosemicarbazone) (FA-DTS), and an omega-phenyl fatty acid analog containing DTS molecule at the para-position, (b) the p-carboxyundecylphenylglyoxal-di (N-methylthiosemicarbazone] (PFA-DTS). FA-DTS was synthesized by the reaction of ethyl diethoxyacetate with ethyl 11-bromonundecanate by successive decarboxylation and hydrolysis and final condensation with N-methylthiosemicarbazide. PFA-DTS was synthesized by the Friedel-Craft acylation of ethyl 11-phenylundecanate, selenium oxidation of the acetophenone derivative, followed by the condensation with N-methylthiosemicarbazide. Radiolabeling of FA-DTS and PFA-DTS with [64Cu]copper acetate was simple, rapid and quantitative. When injected into mice, both compounds were distributed and retained in the myocardium. These results offer a good basis for further development of 62Cu labeled fatty acid analogs.

  14. A New Automated Design Method Based on Machine Learning for CMOS Analog Circuits

    NASA Astrophysics Data System (ADS)

    Moradi, Behzad; Mirzaei, Abdolreza

    2016-11-01

    A new simulation based automated CMOS analog circuit design method which applies a multi-objective non-Darwinian-type evolutionary algorithm based on Learnable Evolution Model (LEM) is proposed in this article. The multi-objective property of this automated design of CMOS analog circuits is governed by a modified Strength Pareto Evolutionary Algorithm (SPEA) incorporated in the LEM algorithm presented here. LEM includes a machine learning method such as the decision trees that makes a distinction between high- and low-fitness areas in the design space. The learning process can detect the right directions of the evolution and lead to high steps in the evolution of the individuals. The learning phase shortens the evolution process and makes remarkable reduction in the number of individual evaluations. The expert designer's knowledge on circuit is applied in the design process in order to reduce the design space as well as the design time. The circuit evaluation is made by HSPICE simulator. In order to improve the design accuracy, bsim3v3 CMOS transistor model is adopted in this proposed design method. This proposed design method is tested on three different operational amplifier circuits. The performance of this proposed design method is verified by comparing it with the evolutionary strategy algorithm and other similar methods.

  15. Design, synthesis and biological evaluation of novel 2-methoxyestradiol analogs as dual selective estrogen receptor modulators (SERMs) and antiangiogenic agents.

    PubMed

    Lao, Kejing; Wang, Yejun; Chen, Mingqi; Zhang, Jingjing; You, Qidong; Xiang, Hua

    2017-10-20

    2-methoxyestradiol is a novel agent showing both anti-angiogenic and vascular disrupting properties. In this study, a series of 11α-substituted 2-methoxyestradiol analogs have been designed and synthesized targeting dual ERα and microtubulin. Biological evaluation was performed on their anti-proliferative activities against 5 different cell lines. The results indicated that most compounds exhibited good activities, in which compound 24c and 30c showed the best activity with low micromolar IC50 (2.73 μM -7.75 μM) in all cell lines. The investigation of ER affinity showed that the majority of the compounds displayed good activity at the concentration of 50 μM. In further mechanism study, it was observed that 24c and 30c could induce G2/M cell cycle arrest as well as significant anti-estrogenic activity. In CAM assay, compound 24c and 30c presented significantly anti-angiogenesis activity comparable with 2-methoxyestradiol. Overall, based on biological activities data, 24c and 30c can be identified as a potential lead molecule which might be of therapeutic importance for cancer treatment. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. Engineering strategy to improve peptide analogs: from structure-based computational design to tumor homing

    NASA Astrophysics Data System (ADS)

    Zanuy, David; Sayago, Francisco J.; Revilla-López, Guillem; Ballano, Gema; Agemy, Lilach; Kotamraju, Venkata Ramana; Jiménez, Ana I.; Cativiela, Carlos; Nussinov, Ruth; Sawvel, April M.; Stucky, Galen; Ruoslahti, Erkki; Alemán, Carlos

    2013-01-01

    We present a chemical strategy to engineer analogs of the tumor-homing peptide CREKA (Cys-Arg-Glu-Lys-Ala), which binds to fibrin and fibrin-associated clotted plasma proteins in tumor vessels (Simberg et al. in Proc Natl Acad Sci USA 104:932-936, 2007) with improved ability to inhibit tumor growth. Computer modeling using a combination of simulated annealing and molecular dynamics were carried out to design targeted replacements aimed at enhancing the stability of the bioactive conformation of CREKA. Because this conformation presents a pocket-like shape with the charged groups of Arg, Glu and Lys pointing outward, non-proteinogenic amino acids α-methyl and N-methyl derivatives of Arg, Glu and Lys were selected, rationally designed and incorporated into CREKA analogs. The stabilization of the bioactive conformation predicted by the modeling for the different CREKA analogs matched the tumor fluorescence results, with tumor accumulation increasing with stabilization. Here we report the modeling, synthetic procedures, and new biological assays used to test the efficacy and utility of the analogs. Combined, our results show how studies based on multi-disciplinary collaboration can converge and lead to useful biomedical advances.

  17. The design, computer modeling, solution structure, and biological evaluation of synthetic analogs of bryostatin 1

    PubMed Central

    Wender, Paul A.; DeBrabander, Jef; Harran, Patrick G.; Jimenez, Juan-Miguel; Koehler, Michael F. T.; Lippa, Blaise; Park, Cheol-Min; Siedenbiedel, Carsten; Pettit, George R.

    1998-01-01

    The bryostatins are a unique family of emerging cancer chemotherapeutic candidates isolated from marine bryozoa. Although the biochemical basis for their therapeutic activity is not known, these macrolactones exhibit high affinities for protein kinase C (PKC) isozymes, compete for the phorbol ester binding site on PKC, and stimulate kinase activity in vitro and in vivo. Unlike the phorbol esters, they are not first-stage tumor promoters. The design, computer modeling, NMR solution structure, PKC binding, and functional assays of a unique class of synthetic bryostatin analogs are described. These analogs (7b, 7c, and 8) retain the putative recognition domain of the bryostatins but are simplified through deletions and modifications in the C4-C14 spacer domain. Computer modeling of an analog prototype (7a) indicates that it exists preferentially in two distinct conformational classes, one in close agreement with the crystal structure of bryostatin 1. The solution structure of synthetic analog 7c was determined by NMR spectroscopy and found to be very similar to the previously reported structures of bryostatins 1 and 10. Analogs 7b, 7c, and 8 bound strongly to PKC isozymes with Ki = 297, 3.4, and 8.3 nM, respectively. Control 7d, like the corresponding bryostatin derivative, exhibited weak PKC affinity, as did the derivative, 9, lacking the spacer domain. Like bryostatin, acetal 7c exhibited significant levels of in vitro growth inhibitory activity (1.8–170 ng/ml) against several human cancer cell lines, providing an important step toward the development of simplified, synthetically accessible analogs of the bryostatins. PMID:9618462

  18. Performance Measurement of a Multi-Level/Analog Ferroelectric Memory Device Design

    NASA Technical Reports Server (NTRS)

    MacLeod, Todd C.; Phillips, Thomas A.; Ho, Fat D.

    2007-01-01

    Increasing the memory density and utilizing the unique characteristics of ferroelectric devices is important in making ferroelectric memory devices more desirable to the consumer. This paper describes the characterization of a design that allows multiple levels to be stored in a ferroelectric based memory cell. It can be used to store multiple bits or analog values in a high speed nonvolatile memory. The design utilizes the hysteresis characteristic of ferroelectric transistors to store an analog value in the memory cell. The design also compensates for the decay of the polarization of the ferroelectric material over time. This is done by utilizing a pair of ferroelectric transistors to store the data. One transistor is used a reference to determinethe amount of decay that has occurred since the pair was programmed. The second transistor stores the analog value as a polarization value between zero and saturated. The design allows digital data to be stored as multiple bits in each memory cell. The number of bits per cell that can be stored will vary with the decay rate of the ferroelectric transistors and the repeatability of polarization between transistors. This paper presents measurements of an actual prototype memory cell. This prototype is not a complete implementation of a device, but instead, a prototype of the storage and retrieval portion of an actual device. The performance of this prototype is presented with the projected performance of the overall device. This memory design will be useful because it allows higher memory density, compensates for the environmental and ferroelectric aging processes, allows analog values to be directly stored in memory, compensates for the thermal and radiation environments associated with space operations, and relies only on existing technologies.

  19. Hetero-ring-expansion design for purine analogs: A theoretical study on the structural, electronic, and excited-state properties

    NASA Astrophysics Data System (ADS)

    Zhang, Laibin; Zhou, Liuzhu; Tian, Jianxiang; Li, Xiaoming

    2014-03-01

    A series of hetero-ring-expanded purine analogs are designed and their structural, electronic and excited-state properties are investigated by DFT calculations. The results indicate that the designed analogs can form stable base pairs with natural counterparts. Compared with natural ones, these size-expanded analogs and corresponding base pairs have smaller ionization potentials and HOMO-LUMO gaps. Furthermore, the A-analogs have ionization potentials even lower than natural G. Finally, the electronic absorption spectra are calculated and the nature of the low-lying excited states is discussed. These observations imply their promising applications as molecular wires and new DNA motifs.

  20. Design, synthesis and evaluation of pH-dependent hydrolysable emetine analogs as treatment for prostate cancer

    PubMed Central

    Akinboye, Emmanuel S.; Rosen, Marc D.; Denmeade, Samuel R.; Kwabi-Addo, Bernard; Bakare, Oladapo

    2013-01-01

    The N-2′ position of the natural product emetine has been derivatized to thiourea, urea, sulfonamide, dithiocarbamate, carbamate and pH responsive hydrolysable amide analogs. In-vitro studies of these analogs in PC3 and LNCaP prostate cancer cell lines showed that the analogs are generally less cytotoxic (average IC50 ranging from 0.079 μM to 10 μM) than emetine (IC50 ranging from 0.0237 to 0.0329 μM). The pH sensitive sodium dithiocarbamate salt 13 and the amide analogs 21, 22, 26 (obtained from maleic and citraconic anhydrides) showed the most promise as acid-activatable prodrugs under mildly acidic conditions found in the cancer micro-environment. These prodrugs released 12 – 83% of emetine at pH 6.5 and 41 – 95% emetine at pH 5.5. Compounds 13 and 26 were further shown to exhibit increased cytotoxicity in PC3 cell culture media that was already below pH 7.0 at the time of treatment. PMID:22867001

  1. The design, fabrication, and test of a new VLSI hybrid analog-digital neural processing element

    NASA Technical Reports Server (NTRS)

    Deyong, Mark R.; Findley, Randall L.; Fields, Chris

    1992-01-01

    A hybrid analog-digital neural processing element with the time-dependent behavior of biological neurons has been developed. The hybrid processing element is designed for VLSI implementation and offers the best attributes of both analog and digital computation. Custom VLSI layout reduces the layout area of the processing element, which in turn increases the expected network density. The hybrid processing element operates at the nanosecond time scale, which enables it to produce real-time solutions to complex spatiotemporal problems found in high-speed signal processing applications. VLSI prototype chips have been designed, fabricated, and tested with encouraging results. Systems utilizing the time-dependent behavior of the hybrid processing element have been simulated and are currently in the fabrication process. Future applications are also discussed.

  2. The design, fabrication, and test of a new VLSI hybrid analog-digital neural processing element

    NASA Technical Reports Server (NTRS)

    Deyong, Mark R.; Findley, Randall L.; Fields, Chris

    1992-01-01

    A hybrid analog-digital neural processing element with the time-dependent behavior of biological neurons has been developed. The hybrid processing element is designed for VLSI implementation and offers the best attributes of both analog and digital computation. Custom VLSI layout reduces the layout area of the processing element, which in turn increases the expected network density. The hybrid processing element operates at the nanosecond time scale, which enables it to produce real-time solutions to complex spatiotemporal problems found in high-speed signal processing applications. VLSI prototype chips have been designed, fabricated, and tested with encouraging results. Systems utilizing the time-dependent behavior of the hybrid processing element have been simulated and are currently in the fabrication process. Future applications are also discussed.

  3. Design of an active ultrastable single-chain insulin analog: synthesis, structure, and therapeutic implications.

    PubMed

    Hua, Qing-xin; Nakagawa, Satoe H; Jia, Wenhua; Huang, Kun; Phillips, Nelson B; Hu, Shi-quan; Weiss, Michael A

    2008-05-23

    Single-chain insulin (SCI) analogs provide insight into the inter-relation of hormone structure, function, and dynamics. Although compatible with wild-type structure, short connecting segments (<3 residues) prevent induced fit upon receptor binding and so are essentially without biological activity. Substantial but incomplete activity can be regained with increasing linker length. Here, we describe the design, structure, and function of a single-chain insulin analog (SCI-57) containing a 6-residue linker (GGGPRR). Native receptor-binding affinity (130 +/- 8% relative to the wild type) is achieved as hindrance by the linker is offset by favorable substitutions in the insulin moiety. The thermodynamic stability of SCI-57 is markedly increased (DeltaDeltaG(u) = 0.7 +/- 0.1 kcal/mol relative to the corresponding two-chain analog and 1.9 +/- 0.1 kcal/mol relative to wild-type insulin). Analysis of inter-residue nuclear Overhauser effects demonstrates that a native-like fold is maintained in solution. Surprisingly, the glycine-rich connecting segment folds against the insulin moiety: its central Pro contacts Val(A3) at the edge of the hydrophobic core, whereas the final Arg extends the A1-A8 alpha-helix. Comparison between SCI-57 and its parent two-chain analog reveals striking enhancement of multiple native-like nuclear Overhauser effects within the tethered protein. These contacts are consistent with wild-type crystal structures but are ordinarily attenuated in NMR spectra of two-chain analogs, presumably due to conformational fluctuations. Linker-specific damping of fluctuations provides evidence for the intrinsic flexibility of an insulin monomer. In addition to their biophysical interest, ultrastable SCIs may enhance the safety and efficacy of insulin replacement therapy in the developing world.

  4. Emergent features and perceptual objects: re-examining fundamental principles in analogical display design.

    PubMed

    Holt, Jerred; Bennett, Kevin B; Flach, John M

    2015-01-01

    Two sets of design principles for analogical visual displays, based on the concepts of emergent features and perceptual objects, are described. An interpretation of previous empirical findings for three displays (bar graph, polar graphic, alphanumeric) is provided from both perspectives. A fourth display (configural coordinate) was designed using principles of ecological interface design (i.e. direct perception). An experiment was conducted to evaluate performance (accuracy and latency of state identification) with these four displays. Numerous significant effects were obtained and a clear rank ordering of performance emerged (from best to worst): configural coordinate, bar graph, alphanumeric and polar graphic. These findings are consistent with principles of design based on emergent features; they are inconsistent with principles based on perceptual objects. Some limitations of the configural coordinate display are discussed and a redesign is provided. Practitioner Summary: Principles of ecological interface design, which emphasise the quality of very specific mappings between domain, display and observer constraints, are described; these principles are applicable to the design of all analogical graphical displays.

  5. Design, development, and fabrication of a electronic analog microminiaturized electronic analog signal to discrete time interval converter

    NASA Technical Reports Server (NTRS)

    Schoenfeld, A. D.; Schuegraf, K. K.

    1973-01-01

    The microminiaturization of an electronic analog signal to discrete time interval converter is presented. Discrete components and integrated circuits comprising the converter were assembled on a thin-film ceramic substrate containing nichrome resistors with gold interconnections. The finished assembly is enclosed in a flat package measuring 3.30 by 4.57 centimeters. The module can be used whenever conversion of analog to digital signals is required, in particular for the purpose of regulation by means of pulse modulation. In conjunction with a precision voltage reference, the module was applied to control the duty cycle of a switching regulator within a temperature range of -55 C to +125 C, and an input voltage range of 10V to 35V. The output-voltage variation was less than + or - 300 parts per million, i.e., less than + or - 3mV for a 10V output.

  6. Digital controller design: Analysis of the annular suspension pointing system. [analog controllers with feedback

    NASA Technical Reports Server (NTRS)

    Kuo, B. C.

    1978-01-01

    The analog controllers of the annular suspension pointing system are designed for control of the chi, phi sub 1, and phi sub 2 bandwidth dynamics through decoupling and pole placement. Since it is virtually impossible to find an equivalent bandwidth of the overall system and establish a general eigenvalue requirement for the system, the subsystem dynamics are decoupled through state feedback and the poles are placed simultaneously to realize the desired bandwidths for the three system components. Decoupling and pole placement are also used to design the closed-loop digital system through approximation.

  7. Redundant Flight-Critical Control System Evaluation: Analog and Digital Systems Failure Analyses and Preflight Test Designs

    DTIC Science & Technology

    1975-01-01

    systems. Specifically , the study evaluates analog and digital electronic designs for implementing a triplex fail-operational flight-critical control...SST Technology Follow-On, phase II) deals with the mechanization of redundant electronic subsystems. Specifically , the study compares analog and...electronics suppliers. Specific areas identified for examination during the FCD task were: • General control function operational performance • Sensor

  8. Application of direct inverse analogy method (DIVA) and viscous design optimization techniques

    NASA Technical Reports Server (NTRS)

    Greff, E.; Forbrich, D.; Schwarten, H.

    1991-01-01

    A direct-inverse approach to the transonic design problem was presented in its initial state at the First International Conference on Inverse Design Concepts and Optimization in Engineering Sciences (ICIDES-1). Further applications of the direct inverse analogy (DIVA) method to the design of airfoils and incremental wing improvements and experimental verification are reported. First results of a new viscous design code also from the residual correction type with semi-inverse boundary layer coupling are compared with DIVA which may enhance the accuracy of trailing edge design for highly loaded airfoils. Finally, the capabilities of an optimization routine coupled with the two viscous full potential solvers are investigated in comparison to the inverse method.

  9. Double negative elastic metamaterial design through electrical-mechanical circuit analogies.

    PubMed

    Pope, Simon A

    2013-07-01

    Previous studies into solid elastic metamaterials which have a simultaneously negative effective bulk modulus and density have proposed designs for materials with relatively narrow bandwidths, because of the reliance on resonators to provide the dispersive material properties. Some of the proposed novel applications for metamaterials, such as invisibility cloaks and sub-wavelength lenses, generally require materials with inherently larger bandwidths for practical exploitation. In this paper, a well-known electromagnetic metamaterial design is used together with the electrical-mechanical circuit analogies to propose a simultaneously double negative elastic metamaterial design which does not suffer from the narrow bandwidth constraints of previous designs. An interesting consequence of the proposed design is that it has an effective wavelength which asymptotically goes to infinity with frequency.

  10. Carbon Nanotubes as FET Channel: Analog Design Optimization considering CNT Parameter Variability

    NASA Astrophysics Data System (ADS)

    Samar Ansari, Mohd.; Tripathi, S. K.

    2017-08-01

    Carbon nanotubes (CNTs), both single-walled as well as multi-walled, have been employed in a plethora of applications pertinent to semiconductor materials and devices including, but not limited to, biotechnology, material science, nanoelectronics and nano-electro mechanical systems (NEMS). The Carbon Nanotube Field Effect Transistor (CNFET) is one such electronic device which effectively utilizes CNTs to achieve a boost in the channel conduction thereby yielding superior performance over standard MOSFETs. This paper explores the effects of variability in CNT physical parameters viz. nanotube diameter, pitch, and number of CNT in the transistor channel, on the performance of a chosen analog circuit. It is further shown that from the analyses performed, an optimal design of the CNFETs can be derived for optimizing the performance of the analog circuit as per a given specification set.

  11. Design and synthesis of a vialinin A analog with a potent inhibitory activity of TNF-α production and its transformation into a couple of bioprobes.

    PubMed

    Ye, Yue Qi; Onose, Jun-ichi; Abe, Naoki; Koshino, Hiroyuki; Takahashi, Shunya

    2012-04-01

    Vialinin A (1) is an extremely potent inhibitor against tumor necrosis factor (TNF)-α production in rat basophilic leukemia (RBL-2H3) cells. This Letter describes the design and synthesis of its advanced analog, 5',6'-dimethyl-1,1':4'1″-terphenyl-2',3',4,4″-tetraol (2) with a comparable inhibitory activity (IC(50)=0.02 nM) to that of 1. The synthesis involved double Suzuki-Miyaura coupling as a key step, and required only five steps from commercially available 3,4-dimethylphenol. For identification of the target molecule, fluorescent and biotinylated derivatives of 2 were prepared through a 'click' coupling process. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Exploiting the dynamic properties of covalent modification cycle for the design of synthetic analog biomolecular circuitry.

    PubMed

    Foo, Mathias; Sawlekar, Rucha; Bates, Declan G

    2016-01-01

    Cycles of covalent modification are ubiquitous motifs in cellular signalling. Although such signalling cycles are implemented via a highly concise set of chemical reactions, they have been shown to be capable of producing multiple distinct input-output mapping behaviours - ultrasensitive, hyperbolic, signal-transducing and threshold-hyperbolic. In this paper, we show how the set of chemical reactions underlying covalent modification cycles can be exploited for the design of synthetic analog biomolecular circuitry. We show that biomolecular circuits based on the dynamics of covalent modification cycles allow (a) the computation of nonlinear operators using far fewer chemical reactions than purely abstract designs based on chemical reaction network theory, and (b) the design of nonlinear feedback controllers with strong performance and robustness properties. Our designs provide a more efficient route for translation of complex circuits and systems from chemical reactions to DNA strand displacement-based chemistry, thus facilitating their experimental implementation in future Synthetic Biology applications.

  13. Designed cell consortia as fragrance-programmable analog-to-digital converters.

    PubMed

    Müller, Marius; Ausländer, Simon; Spinnler, Andrea; Ausländer, David; Sikorski, Julian; Folcher, Marc; Fussenegger, Martin

    2017-03-01

    Synthetic biology advances the rational engineering of mammalian cells to achieve cell-based therapy goals. Synthetic gene networks have nearly reached the complexity of digital electronic circuits and enable single cells to perform programmable arithmetic calculations or to provide dynamic remote control of transgenes through electromagnetic waves. We designed a synthetic multilayered gaseous-fragrance-programmable analog-to-digital converter (ADC) allowing for remote control of digital gene expression with 2-bit AND-, OR- and NOR-gate logic in synchronized cell consortia. The ADC consists of multiple sampling-and-quantization modules sensing analog gaseous fragrance inputs; a gas-to-liquid transducer converting fragrance intensity into diffusible cell-to-cell signaling compounds; a digitization unit with a genetic amplifier circuit to improve the signal-to-noise ratio; and recombinase-based digital expression switches enabling 2-bit processing of logic gates. Synthetic ADCs that can remotely control cellular activities with digital precision may enable the development of novel biosensors and may provide bioelectronic interfaces synchronizing analog metabolic pathways with digital electronics.

  14. Design and synthesis of a biotinylated probe of COX-2 inhibitor nimesulide analog JCC76.

    PubMed

    Zhong, Bo; Lama, Rati; Smith, Kerri M; Xu, Yan; Su, Bin

    2011-09-15

    JCC76 is a derivative of cyclooxygenase-2(COX-2) selective inhibitor nimesulide and exhibits potent anti-breast cancer activity. It selectively induces apoptosis of Her2 positive breast cancer cells. However, the specific molecular targets of JCC76 still remain unclear, which significantly withdraw the further drug development of JCC76. To identify the molecular targets of JCC76, a six carbon linker and biotin conjugated JCC76 probe was designed and synthesized. The anti-proliferation activity of the probe and its analogs was evaluated. Published by Elsevier Ltd.

  15. Design of Combustor for Long-range Ram-jet Engine and Performance of Rectangular Analog

    NASA Technical Reports Server (NTRS)

    Rayle, Warren D; Koch, Richard G

    1954-01-01

    The report describes the design of a piloted combustor intended for a ram-jet engine of long flight range. The unit comprises a large annular basket of V-type cross-section, the inner surface of which is slotted and bent into small V-gutters. At the trailing edge of the basket, eight V-gutters are used to propagate the flame into the main stream. A rectangular analog of this combustor was tested at air-flow conditions corresponding to those that might be obtained during cruise. At these conditions, combustion efficiencies of as much as 90 percent were calculated for the combustor at the design equivalence ratio of 0.52. The performance of the unit was relatively insensitive to mounting and flow variables; the greatest effect on efficiency was that of the manner and location of the fuel injection. A full-scale version of this combustor has been designed for a 48-inch-diameter engine.

  16. The design, synthesis and biological evaluation of novel thiamin diphosphate analog inhibitors against the pyruvate dehydrogenase multienzyme complex E1 from Escherichia coli.

    PubMed

    Feng, Lingling; He, Junbo; He, Haifeng; Zhao, Lulu; Deng, Lingfu; Zhang, Li; Zhang, Lin; Ren, Yanliang; Wan, Jian; He, Hongwu

    2014-11-28

    Pyruvate dehydrogenase multienzyme complex E1 (PDHc E1) is a potential target enzyme when looking for inhibitors to combat microbial disease. In this study, we designed and synthesized a series of novel thiamin diphosphate (ThDP) analogs with triazole ring and oxime ether moieties as potential inhibitors of PDHc E1. Their inhibitory activities against PDHc E1 were examined both in vitro and in vivo. Most of the tested compounds exhibited moderate inhibitory activities against PDHc E1 (IC50 = 6.1-75.5 μM). The potent inhibitors 4g, 4h and 4j, had strong inhibitory activities with IC50 values of 6.7, 6.9 and 6.1 μM against PDHc E1 in vitro and with inhibition rates of 35%, 50% and 33% at 100 μg mL(-1) against Gibberella zeae in vivo, respectively. The binding mode of 4j to PDHc E1 was analyzed by a molecular docking method. Furthermore, the possible interactions of the important residues of PDHc E1 with compound 4j were examined by site-directed mutagenesis, enzymatic assays and spectral fluorescence studies. The theoretical and experimental results are in good agreement and suggest that compound 4j could be used as a lead compound for further optimization, and may have potential as a new microbicide.

  17. The Designer Methcathinone Analogs, Mephedrone and Methylone, are Substrates for Monoamine Transporters in Brain Tissue

    PubMed Central

    Baumann, Michael H; Ayestas, Mario A; Partilla, John S; Sink, Jacqueline R; Shulgin, Alexander T; Daley, Paul F; Brandt, Simon D; Rothman, Richard B; Ruoho, Arnold E; Cozzi, Nicholas V

    2012-01-01

    The nonmedical use of ‘designer' cathinone analogs, such as 4-methylmethcathinone (mephedrone) and 3,4-methylenedioxymethcathinone (methylone), is increasing worldwide, yet little information is available regarding the mechanism of action for these drugs. Here, we employed in vitro and in vivo methods to compare neurobiological effects of mephedrone and methylone with those produced by the structurally related compounds, 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine. In vitro release assays using rat brain synaptosomes revealed that mephedrone and methylone are nonselective substrates for plasma membrane monoamine transporters, similar to MDMA in potency and selectivity. In vivo microdialysis in rat nucleus accumbens showed that i.v. administration of 0.3 and 1.0 mg/kg of mephedrone or methylone produces dose-related increases in extracellular dopamine and serotonin (5-HT), with the magnitude of effect on 5-HT being greater. Both methcathinone analogs were weak motor stimulants when compared with methamphetamine. Repeated administrations of mephedrone or methylone (3.0 and 10.0 mg/kg, s.c., 3 doses) caused hyperthermia but no long-term change in cortical or striatal amines, whereas similar treatment with MDMA (2.5 and 7.5 mg/kg, s.c., 3 doses) evoked robust hyperthermia and persistent depletion of cortical and striatal 5-HT. Our data demonstrate that designer methcathinone analogs are substrates for monoamine transporters, with a profile of transmitter-releasing activity comparable to MDMA. Dopaminergic effects of mephedrone and methylone may contribute to their addictive potential, but this hypothesis awaits confirmation. Given the widespread use of mephedrone and methylone, determining the consequences of repeated drug exposure warrants further study. PMID:22169943

  18. Low-voltage and low-power circuit design for mixed analog/digital systems in portable equipment

    NASA Astrophysics Data System (ADS)

    Matsuzawa, Akira

    1994-04-01

    This paper describes low-voltage and low-power (LV/LP) circuit design for both analog LSI's and digital LSI's which are used in mixed analog/digital systems in portable equipment. We review some LV/LP circuits used in digital LSI's, such as general logic gate, DSP, and DRAM, and others used in analog LSI's, such as operational amplifiers, video-signal processing circuits, A/D and D/A converters, filters, and RF circuits, along with a wide range of items used in recently developed LSI's. Since analog circuits have fundamental difficulties for reducing the operating voltage and the power consumption, in spite of recent progress in LV/LP circuit techniques, these difficulties will be a major issue for decreasing the total power consumption of some mixed analog/digital systems used in portable equipment.

  19. Macromodeling for analog design and robustness boosting in bio-inspired computing models

    NASA Astrophysics Data System (ADS)

    Cuadri, J.; Linan, G.; Roca, E.; Rodriguez-Vazquez, A.

    2005-06-01

    Setting specifications for the electronic implementation of biological neural-network-like vision systems on-chip is not straightforward, neither it is to simulate the resulting circuit. The structure of these systems leads to a netlist of more than 100.000 nodes for a small array of 100x150 pixels. Moreover, introducing an optical input in the low level simulation is nowadays not feasible with standard electrical simulation environments. Given that, to accomplish the task of integrating those systems in silicon to build compact, low power consuming, and reliable systems, a previous step in the standard analog electronic design flux should be introduced. Here a methodology to make the translation from the biological model to circuit-level specifications for electronic design is proposed. The purpose is to include non ideal effects as mismatching, noise, leakages, supply degradation, feedthrough, and temperature of operation in a high level description of the implementation, in order to accomplish behavioural simulations that require less computational effort and resources. A particular case study is presented, the analog electronic implementation of the locust"s Lobula Giant Movement Detector (LGMD), a neural structure that fires a collision alarm based on visual information. The final goal is a collision threat detection vision system on-chip for automotive applications.

  20. Design and activity of a cyclic mini-β-defensin analog: a novel antimicrobial tool

    PubMed Central

    Scudiero, Olga; Nigro, Ersilia; Cantisani, Marco; Colavita, Irene; Leone, Marilisa; Mercurio, Flavia Anna; Galdiero, Massimiliano; Pessi, Antonello; Daniele, Aurora; Salvatore, Francesco; Galdiero, Stefania

    2015-01-01

    We have designed a cyclic 17-amino acid β-defensin analog featuring a single disulfide bond. This analog, designated “AMC” (ie, antimicrobial cyclic peptide), combines the internal hydrophobic domain of hBD1 and the C-terminal charged region of hBD3. The novel peptide was synthesized and characterized by nuclear magnetic resonance spectroscopy. The antimicrobial activities against gram-positive and gram-negative bacteria as well as against herpes simplex virus type 1 were analyzed. The cytotoxicity and serum stability were assessed. Nuclear magnetic resonance of AMC in aqueous solution suggests that the structure of the hBD1 region, although not identical, is preserved. Like the parent defensins, AMC is not cytotoxic for CaCo-2 cells. Interestingly, AMC retains the antibacterial activity of the parent hBD1 and hBD3 against Pseudomonas aeruginosa, Enterococcus faecalis, and Escherichia coli, and exerts dose-dependent activity against herpes simplex virus type 1. Moreover, while the antibacterial and antiviral activities of the oxidized and reduced forms of the parent defensins are similar, those of AMC are significantly different, and oxidized AMC is also considerably more stable in human serum. Taken together, our data also suggest that this novel peptide may be added to the arsenal of tools available to combat antibiotic-resistant infectious diseases, particularly because of its potential for encapsulation in a nanomedicine vector. PMID:26508857

  1. Designed abscisic acid analogs as antagonists of PYL-PP2C receptor interactions.

    PubMed

    Takeuchi, Jun; Okamoto, Masanori; Akiyama, Tomonori; Muto, Takuya; Yajima, Shunsuke; Sue, Masayuki; Seo, Mitsunori; Kanno, Yuri; Kamo, Tsunashi; Endo, Akira; Nambara, Eiji; Hirai, Nobuhiro; Ohnishi, Toshiyuki; Cutler, Sean R; Todoroki, Yasushi

    2014-06-01

    The plant stress hormone abscisic acid (ABA) is critical for several abiotic stress responses. ABA signaling is normally repressed by group-A protein phosphatases 2C (PP2Cs), but stress-induced ABA binds Arabidopsis PYR/PYL/RCAR (PYL) receptors, which then bind and inhibit PP2Cs. X-ray structures of several receptor-ABA complexes revealed a tunnel above ABA's 3' ring CH that opens at the PP2C binding interface. Here, ABA analogs with sufficiently long 3' alkyl chains were predicted to traverse this tunnel and block PYL-PP2C interactions. To test this, a series of 3'-alkylsulfanyl ABAs were synthesized with different alkyl chain lengths. Physiological, biochemical and structural analyses revealed that a six-carbon alkyl substitution produced a potent ABA antagonist that was sufficiently active to block multiple stress-induced ABA responses in vivo. This study provides a new approach for the design of ABA analogs, and the results validated structure-based design for this target class.

  2. Design of pressure-driven microfluidic networks using electric circuit analogy.

    PubMed

    Oh, Kwang W; Lee, Kangsun; Ahn, Byungwook; Furlani, Edward P

    2012-02-07

    This article reviews the application of electric circuit methods for the analysis of pressure-driven microfluidic networks with an emphasis on concentration- and flow-dependent systems. The application of circuit methods to microfluidics is based on the analogous behaviour of hydraulic and electric circuits with correlations of pressure to voltage, volumetric flow rate to current, and hydraulic to electric resistance. Circuit analysis enables rapid predictions of pressure-driven laminar flow in microchannels and is very useful for designing complex microfluidic networks in advance of fabrication. This article provides a comprehensive overview of the physics of pressure-driven laminar flow, the formal analogy between electric and hydraulic circuits, applications of circuit theory to microfluidic network-based devices, recent development and applications of concentration- and flow-dependent microfluidic networks, and promising future applications. The lab-on-a-chip (LOC) and microfluidics community will gain insightful ideas and practical design strategies for developing unique microfluidic network-based devices to address a broad range of biological, chemical, pharmaceutical, and other scientific and technical challenges.

  3. Root analog zirconia implants: true anatomical design for molar replacement--a case report.

    PubMed

    Pirker, Wolfgang; Kocher, Alfred

    2011-01-01

    Replacement of lost teeth using oral implants is an accepted treatment modality with well-documented high long-term success rates. Conventional screw- or threaded cylinder-type implants have been used almost exclusively. Their incongruence with the extraction socket necessitates the use of a barrier membrane or bone augmentation to prevent down-growth of connective tissue or epithelium between the implant and socket. Although some minor changes in implant design have been made, the neck and abutment connection areas have not changed much in the past 30 years. Custom-made root analog implants have been employed clinically in rare instances; however, they yielded failure rates of up to 96% at 1 year of follow-up. So far, ovoid implants are the closest in design regarding resemblance to the natural tooth anatomy. Root analog zirconia implants with macroretentions were developed and produced for immediate single-stage replacement of missing or hopeless teeth. This article discusses the treatment and 3-year follow-up of a patient with such an implant for replacement of a maxillary molar.

  4. Design and activity of a cyclic mini-β-defensin analog: a novel antimicrobial tool.

    PubMed

    Scudiero, Olga; Nigro, Ersilia; Cantisani, Marco; Colavita, Irene; Leone, Marilisa; Mercurio, Flavia Anna; Galdiero, Massimiliano; Pessi, Antonello; Daniele, Aurora; Salvatore, Francesco; Galdiero, Stefania

    2015-01-01

    We have designed a cyclic 17-amino acid β-defensin analog featuring a single disulfide bond. This analog, designated "AMC" (ie, antimicrobial cyclic peptide), combines the internal hydrophobic domain of hBD1 and the C-terminal charged region of hBD3. The novel peptide was synthesized and characterized by nuclear magnetic resonance spectroscopy. The antimicrobial activities against gram-positive and gram-negative bacteria as well as against herpes simplex virus type 1 were analyzed. The cytotoxicity and serum stability were assessed. Nuclear magnetic resonance of AMC in aqueous solution suggests that the structure of the hBD1 region, although not identical, is preserved. Like the parent defensins, AMC is not cytotoxic for CaCo-2 cells. Interestingly, AMC retains the antibacterial activity of the parent hBD1 and hBD3 against Pseudomonas aeruginosa, Enterococcus faecalis, and Escherichia coli, and exerts dose-dependent activity against herpes simplex virus type 1. Moreover, while the antibacterial and antiviral activities of the oxidized and reduced forms of the parent defensins are similar, those of AMC are significantly different, and oxidized AMC is also considerably more stable in human serum. Taken together, our data also suggest that this novel peptide may be added to the arsenal of tools available to combat antibiotic-resistant infectious diseases, particularly because of its potential for encapsulation in a nanomedicine vector.

  5. Path programmable logic: A structured design method for digital and/or mixed analog integrated circuits

    NASA Technical Reports Server (NTRS)

    Taylor, B.

    1990-01-01

    The design of Integrated Circuits has evolved past the black art practiced by a few semiconductor companies to a world wide community of users. This was basically accomplished by the development of computer aided design tools which were made available to this community. As the tools matured into different components of the design task they were accepted into the community at large. However, the next step in this evolution is being ignored by the large tool vendors hindering the continuation of this process. With system level definition and simulation through the logic specification well understood, why is the physical generation so blatantly ignored. This portion of the development is still treated as an isolated task with information being passed from the designer to the layout function. Some form of result given back but it severely lacks full definition of what has transpired. The level of integration in I.C.'s for tomorrow, whether through new processes or applications will require higher speeds, increased transistor density, and non-digital performance which can only be achieved through attention to the physical implementation.

  6. Using an Analogical Thinking Model as an Instructional Tool to Improve Student Cognitive Ability in Architecture Design Learning Process

    ERIC Educational Resources Information Center

    Wu, Yun-Wu; Weng, Kuo-Hua

    2013-01-01

    Lack of creativity is a problem often plaguing students from design-related departments. Therefore, this study is intended to incorporate analogical thinking in the education of architecture design to enhance students' learning and their future career performance. First, this study explores the three aspects of architecture design curricula,…

  7. Using an Analogical Thinking Model as an Instructional Tool to Improve Student Cognitive Ability in Architecture Design Learning Process

    ERIC Educational Resources Information Center

    Wu, Yun-Wu; Weng, Kuo-Hua

    2013-01-01

    Lack of creativity is a problem often plaguing students from design-related departments. Therefore, this study is intended to incorporate analogical thinking in the education of architecture design to enhance students' learning and their future career performance. First, this study explores the three aspects of architecture design curricula,…

  8. Novel designed VmCT1 analogs with increased antimicrobial activity.

    PubMed

    Pedron, Cibele Nicolaski; Torres, Marcelo Der Torossian; Lima, Julia Aparecida da Silva; Silva, Pedro Ismael; Silva, Fernanda Dias; Oliveira, Vani Xavier

    2017-01-27

    Antimicrobial peptides are biologically active molecules produced by a wide range of organisms as an essential component of the innate immune response. They have recently attracted great interest, since they have antimicrobial activity against a broad spectrum of microorganisms. VmCT1 is a cationic peptide from the venom of Vaejovis mexicanus smithi scorpions, which presents antibacterial activity and tends to helical structures. Its analogs were synthesized, characterized and the conformational studies were performed by circular dichroism. The peptides were designed to verify if the single and double substitutions proposed at the hydrophilic and hydrophobic portions of the amphipathic structure would alter antimicrobial activity against Gram-negative and Gram-positive bacteria, yeast and filamentous fungus, besides the hemolytic activity in human erythrocytes. Total charge of the peptides were modified from +2 to +3 by the introduction of a Lysine residue in the hydrophilic face of the amphiphilic helical structure leading to enhanced antimicrobial activity. [K](11)-VmCT1-NH2 presented the lower MIC value against the microorganisms (from 0.39 to 6.25 μmol L(-1)), however it showed higher hemolytic activity. The other Lysine-substituted analogs presented also lower MIC values ranging from 0.39 to 25 μmol L(-1) for the microorganisms assessed. The circular dichroism spectra analyses suggest that the Lysine-substituted analogs tend to adopt helical structures in trifluoroethanol solution and vesicles (fH: 0.43-1), however they were coiled in water. Alanine substitution by a Glutamic acid residue in the hydrophilic face promotes the increase of polar angle in [E](4)-VmCT1-NH2 analog, which was important to led lower hemolytic activity (MHC value = 25 μmol L(-1)). [W](9)-VmCT1-NH2 and [E](4)[W](9)-VmCT1-NH2 were designed to favors hydrophobic interactions by the introduction of Tryptophan residue. [W](9)-VmCT1-NH2 presented MIC values lower or similar than

  9. Design of a wideband CMOS impedance spectroscopy ASIC analog front-end for multichannel biosensor interfaces.

    PubMed

    Valente, Virgilio; Dai Jiang; Demosthenous, Andreas

    2015-08-01

    This paper presents the preliminary design and simulation of a flexible and programmable analog front-end (AFE) circuit with current and voltage readout capabilities for electric impedance spectroscopy (EIS). The AFE is part of a fully integrated multifrequency EIS platform. The current readout comprises of a transimpedance stage and an automatic gain control (AGC) unit designed to accommodate impedance changes larger than 3 order of magnitude. The AGC is based on a dynamic peak detector that tracks changes in the input current over time and regulates the gain of a programmable gain amplifier in order to optimise the signal-to-noise ratio. The system works up to 1 MHz. The voltage readout consists of a 2 stages of fully differential current-feedback instrumentation amplifier which provide 100 dB of CMRR and a programmable gain up to 20 V/V per stage with a bandwidth in excess of 10MHz.

  10. Antitumor Agents 250.† Design and Synthesis of New Curcumin Analogs as Potential Anti-Prostate Cancer Agents

    PubMed Central

    Lin, Li; Shi, Qian; Nyarko, Alexander K.; Bastow, Kenneth F.; Wu, Chin-Chung; Su, Ching-Yuan; Shih, Charles C.-Y; Lee, Kuo-Hsiung

    2008-01-01

    In a continuing study of curcumin analogs as potential drug candidates to treat prostate cancer at both androgen-dependent and androgen-refractory stages, we designed and synthesized over 40 new analogs classified into four series: monophenyl analogs (series A), heterocycle-containing analogs (series B), analogs bearing various substituents on the phenyl rings (series C) and analogs with various linkers (series D). These new compounds were tested for cytotoxicity against two human prostate cancer cell lines, androgen-dependent LNCaP and androgen-independent PC-3. Antiandrogenic activity was also evaluated in LNCaP cells and PC-3 cells transfected with wild-type androgen receptor. Ten compounds possessed potent cytotoxicity against both LNCaP and PC-3 cells; seven only against LNCaP; and one solely against PC-3. This study established an advanced structure-activity relationship (SAR), and these correlations will guide the further design of new curcumin analogs with better anti-prostate cancer activity. PMID:16789753

  11. Design of an insulin analog with enhanced receptor binding selectivity: rationale, structure, and therapeutic implications.

    PubMed

    Zhao, Ming; Wan, Zhu-li; Whittaker, Linda; Xu, Bin; Phillips, Nelson B; Katsoyannis, Panayotis G; Ismail-Beigi, Faramarz; Whittaker, Jonathan; Weiss, Michael A

    2009-11-13

    Insulin binds with high affinity to the insulin receptor (IR) and with low affinity to the type 1 insulin-like growth factor (IGF) receptor (IGFR). Such cross-binding, which reflects homologies within the insulin-IGF signaling system, is of clinical interest in relation to the association between hyperinsulinemia and colorectal cancer. Here, we employ nonstandard mutagenesis to design an insulin analog with enhanced affinity for the IR but reduced affinity for the IGFR. Unnatural amino acids were introduced by chemical synthesis at the N- and C-capping positions of a recognition alpha-helix (residues A1 and A8). These sites adjoin the hormone-receptor interface as indicated by photocross-linking studies. Specificity is enhanced more than 3-fold on the following: (i) substitution of Gly(A1) by D-Ala or D-Leu, and (ii) substitution of Thr(A8) by diaminobutyric acid (Dab). The crystal structure of [D-Ala(A1),Dab(A8)]insulin, as determined within a T(6) zinc hexamer to a resolution of 1.35 A, is essentially identical to that of human insulin. The nonstandard side chains project into solvent at the edge of a conserved receptor-binding surface shared by insulin and IGF-I. Our results demonstrate that modifications at this edge discriminate between IR and IGFR. Because hyperinsulinemia is typically characterized by a 3-fold increase in integrated postprandial insulin concentrations, we envisage that such insulin analogs may facilitate studies of the initiation and progression of cancer in animal models. Future development of clinical analogs lacking significant IGFR cross-binding may enhance the safety of insulin replacement therapy in patients with type 2 diabetes mellitus at increased risk of colorectal cancer.

  12. Effective Low-Power Wearable Wireless Surface EMG Sensor Design Based on Analog-Compressed Sensing

    PubMed Central

    Balouchestani, Mohammadreza; Krishnan, Sridhar

    2014-01-01

    Surface Electromyography (sEMG) is a non-invasive measurement process that does not involve tools and instruments to break the skin or physically enter the body to investigate and evaluate the muscular activities produced by skeletal muscles. The main drawbacks of existing sEMG systems are: (1) they are not able to provide real-time monitoring; (2) they suffer from long processing time and low speed; (3) they are not effective for wireless healthcare systems because they consume huge power. In this work, we present an analog-based Compressed Sensing (CS) architecture, which consists of three novel algorithms for design and implementation of wearable wireless sEMG bio-sensor. At the transmitter side, two new algorithms are presented in order to apply the analog-CS theory before Analog to Digital Converter (ADC). At the receiver side, a robust reconstruction algorithm based on a combination of ℓ1-ℓ1-optimization and Block Sparse Bayesian Learning (BSBL) framework is presented to reconstruct the original bio-signals from the compressed bio-signals. The proposed architecture allows reducing the sampling rate to 25% of Nyquist Rate (NR). In addition, the proposed architecture reduces the power consumption to 40%, Percentage Residual Difference (PRD) to 24%, Root Mean Squared Error (RMSE) to 2%, and the computation time from 22 s to 9.01 s, which provide good background for establishing wearable wireless healthcare systems. The proposed architecture achieves robust performance in low Signal-to-Noise Ratio (SNR) for the reconstruction process. PMID:25526357

  13. Effective low-power wearable wireless surface EMG sensor design based on analog-compressed sensing.

    PubMed

    Balouchestani, Mohammadreza; Krishnan, Sridhar

    2014-12-17

    Surface Electromyography (sEMG) is a non-invasive measurement process that does not involve tools and instruments to break the skin or physically enter the body to investigate and evaluate the muscular activities produced by skeletal muscles. The main drawbacks of existing sEMG systems are: (1) they are not able to provide real-time monitoring; (2) they suffer from long processing time and low speed; (3) they are not effective for wireless healthcare systems because they consume huge power. In this work, we present an analog-based Compressed Sensing (CS) architecture, which consists of three novel algorithms for design and implementation of wearable wireless sEMG bio-sensor. At the transmitter side, two new algorithms are presented in order to apply the analog-CS theory before Analog to Digital Converter (ADC). At the receiver side, a robust reconstruction algorithm based on a combination of ℓ1-ℓ1-optimization and Block Sparse Bayesian Learning (BSBL) framework is presented to reconstruct the original bio-signals from the compressed bio-signals. The proposed architecture allows reducing the sampling rate to 25% of Nyquist Rate (NR). In addition, the proposed architecture reduces the power consumption to 40%, Percentage Residual Difference (PRD) to 24%, Root Mean Squared Error (RMSE) to 2%, and the computation time from 22 s to 9.01 s, which provide good background for establishing wearable wireless healthcare systems. The proposed architecture achieves robust performance in low Signal-to-Noise Ratio (SNR) for the reconstruction process.

  14. Design and synthesis of benzimidazole analogs endowed with oxadiazole as selective COX-2 inhibitor.

    PubMed

    Rathore, Ankita; Rahman, Mujeeb Ur; Siddiqui, Anees Ahamad; Ali, Abuzer; Shaharyar, Mohammad

    2014-12-01

    New molecules of benzimidazole endowed with oxadiazole were designed and synthesized from 2-(2-((pyrimidin-2-ylthio)methyl)-1H-benzo[d]imidazol-1-yl)acetohydrazide as 1-((5-substituted alkyl/aryl-1,3,4-oxadiazol-2-yl)methyl)-2-((pyrimidin-2-ylthio)methyl)-1H-benzimidazoles (5a-r) with the aim to acquire selective cyclooxygenase (COX-2) inhibitor activity. The synthesized compounds were screened by in vitro cyclooxygenase assays to determine COX-1 and COX-2 inhibitory potency and the results showed that they had good-to-remarkable activity with an IC50 range of 11.6-56.1 µM. The most active compounds were further screened for their in vivo anti-inflammatory activity by using the carrageenan-induced rat paw edema model. In vitro anticancer activities of the hybrid compounds were assessed by the National Cancer Institute (NCI), USA, against 60 human cell lines, and the results showed a good spectrum. Compound 5l exhibited significant COX-2 inhibition with an IC50 value of 8.2 µM and a percent protection of 68.4%. Compound 5b evinced moderate cytotoxicity toward the UO-31 cell line of renal cancer. A docking study was performed using Maestro 9.0, to provide the binding mode into the binding sites of the cyclooxygenase enzyme. Hopefully, in the future, compound 5l could serve as a lead compound for developing new COX-2 inhibitors.

  15. Structure-based design and synthesis of a bivalent iminobiotin analog showing strong affinity toward a low immunogenic streptavidin mutant.

    PubMed

    Kawato, Tatsuya; Mizohata, Eiichi; Shimizu, Yohei; Meshizuka, Tomohiro; Yamamoto, Tomohiro; Takasu, Noriaki; Matsuoka, Masahiro; Matsumura, Hiroyoshi; Kodama, Tatsuhiko; Kanai, Motomu; Doi, Hirofumi; Inoue, Tsuyoshi; Sugiyama, Akira

    2015-01-01

    The streptavidin/biotin interaction has been widely used as a useful tool in research fields. For application to a pre-targeting system, we previously developed a streptavidin mutant that binds to an iminobiotin analog while abolishing affinity for natural biocytin. Here, we design a bivalent iminobiotin analog that shows 1000-fold higher affinity than before, and determine its crystal structure complexed with the mutant protein.

  16. Analog series-based scaffolds: computational design and exploration of a new type of molecular scaffolds for medicinal chemistry.

    PubMed

    Dimova, Dilyana; Stumpfe, Dagmar; Hu, Ye; Bajorath, Jürgen

    2016-12-01

    Computational design of and systematic search for a new type of molecular scaffolds termed analog series-based scaffolds. From currently available bioactive compounds, analog series were systematically extracted, key compounds identified and new scaffolds isolated from them. Using our computational approach, more than 12,000 scaffolds were extracted from bioactive compounds. A new scaffold definition is introduced and a computational methodology developed to systematically identify such scaffolds, yielding a large freely available scaffold knowledge base.

  17. ASD IC for the thin gap chambers in the LHC Atlas experiment

    SciTech Connect

    Sasaki, Osamu; Yoshida, Mitsuhiro

    1999-12-01

    An amplifier-shaper-discriminator (ASD) chip was designed and built for Thin Gap Chambers in the forward muon trigger system of the LHC Atlas experiment. The ASD IC uses SONY Analog Master Slice bipolar technology. The IC contains 4 channels in a QFP48 package. The gain of its first stage (preamplifier) is approximately 0.8V/pC and output from the preamplifier is received by a shaper (main-amplifier) with a gain of 7. The baseline restoration circuit is incorporated in the main-amplifier. The threshold voltage for discriminator section is common to the 4 channels and their digital output level is LVDS-compatible. The IC also has analog output of the preamplifier. The equivalent noise charge at input capacitance of 150 pF is around 7,500 electrons. The power dissipation with LDVS outputs (100 {Omega} load) is 59mW/ch.

  18. Guidelines for Design and Test of a Built-In Self Test (BIST) Circuit For Space Radiation Studies of High-Speed IC Technologies

    NASA Technical Reports Server (NTRS)

    Carts, M. A.; Marshall, P. W.; Reed, R.; Curie, S.; Randall, B.; LaBel, K.; Gilbert, B.; Daniel, E.

    2006-01-01

    Serial Bit Error Rate Testing under radiation to characterize single particle induced errors in high-speed IC technologies generally involves specialized test equipment common to the telecommunications industry. As bit rates increase, testing is complicated by the rapidly increasing cost of equipment able to test at-speed. Furthermore as rates extend into the tens of billions of bits per second test equipment ceases to be broadband, a distinct disadvantage for exploring SEE mechanisms in the target technologies. In this presentation the authors detail the testing accomplished in the CREST project and apply the knowledge gained to establish a set of guidelines suitable for designing arbitrarily high speed radiation effects tests.

  19. Computer modeling of complete IC fabrication process

    NASA Astrophysics Data System (ADS)

    Dutton, Robert W.

    1987-05-01

    The development of fundamental algorithms for process and device modeling as well as novel integration of the tools for advanced Integrated Circuit (IC) technology design is discussed. The development of the first complete 2D process simulator, SUPREM 4, is reported. The algorithms are discussed as well as application to local-oxidation and extrinsic diffusion conditions which occur in CMOS AND BiCMOS technologies. The evolution of 1D (SEDAN) and 2D (PISCES) device analysis is discussed. The application of SEDAN to a variety of non-silicon technologies (GaAs and HgCdTe) are considered. A new multi-window analysis capability for PISCES which exploits Monte Carlo analysis of hot carriers has been demonstrated and used to characterize a variety of silicon MOSFET and GaAs MESFET effects. A parallel computer implementation of PISCES has been achieved using a Hypercube architecture. The PISCES program has been used for a range of important device studies including: latchup, analog switch analysis, MOSFET capacitance studies and bipolar transient device for ECL gates. The program is broadly applicable to RAM and BiCMOS technology analysis and design. In the analog switch technology area this research effort has produced a variety of important modeling and advances.

  20. IC Associated Conditions

    MedlinePlus

    ... marked by various painful vulvovaginal symptoms, is the fourth most common IC-related condition. It is thought ... about these and other related conditions. Revised Thursday, July 7th, 2016 About IC What is Interstitial Cystitis ( ...

  1. IC Treatment: Antihistamines

    MedlinePlus

    ... IC Epidemiology (RICE) Study Boston Area Community Health (BACH) Survey ICA Pilot Research Program Funding Opportunities Clinical ... IC Epidemiology (RICE) Study Boston Area Community Health (BACH) Survey ICA Pilot Research Program Funding Opportunities Clinical ...

  2. Pregnancy and IC

    MedlinePlus

    ... IC Epidemiology (RICE) Study Boston Area Community Health (BACH) Survey ICA Pilot Research Program Funding Opportunities Clinical ... IC Epidemiology (RICE) Study Boston Area Community Health (BACH) Survey ICA Pilot Research Program Funding Opportunities Clinical ...

  3. SPROC: A multiple-processor DSP IC

    NASA Technical Reports Server (NTRS)

    Davis, R.

    1991-01-01

    A large, single-chip, multiple-processor, digital signal processing (DSP) integrated circuit (IC) fabricated in HP-Cmos34 is presented. The innovative architecture is best suited for analog and real-time systems characterized by both parallel signal data flows and concurrent logic processing. The IC is supported by a powerful development system that transforms graphical signal flow graphs into production-ready systems in minutes. Automatic compiler partitioning of tasks among four on-chip processors gives the IC the signal processing power of several conventional DSP chips.

  4. High performance liquid chromatography enantioseparation of the novel designed mexiletine derivatives and its analogs.

    PubMed

    Zheng, Chengzhen; Zhang, Datong; Wu, Qi; Lin, Xianfu

    2011-02-01

    A series of novel designed mexiletine derivatives and its analogs were prepared, the structures were confirmed by Nuclear Magnetic Resonance (NMR), Fourier Transform Infrared Spectroscopy (FTIR), and Electrospray Ionization-Mass Spectrometry (ESI-MS), and the enantioseparations were performed on polysaccharide-based chiral stationary phase (CSP), Chiralcel OD-H, and Chiralcel OJ-H, under normal-phase mode. The effects of the concentration of isopropanol in the mobile phase were studied, seven of the eight enantiomers got baseline separation on Chiralcel OD-H, and five of the eight enantiomers got successfully separation on Chiralcel OJ-H. The effects of structural features were also discussed. Copyright © 2010 Wiley-Liss, Inc.

  5. SEMICONDUCTOR INTEGRATED CIRCUITS Design of an analog front-end for ambulatory biopotential measurement systems

    NASA Astrophysics Data System (ADS)

    Jiazhen, Wang; Jun, Xu; Lirong, Zheng; Junyan, Ren

    2010-10-01

    A continuously tunable gain and bandwidth analog front-end for ambulatory biopotential measurement systems is presented. The front-end circuit is capable of amplifying and conditioning different biosignals. To optimize the power consumption and simplify the system architecture, the front-end only adopts two-stage amplifiers. In addition, careful design eliminates the need for chopping circuits. The input-referred noise of the system is only 1.19 μVrms (0.48-2000 Hz). The chip is fabricated via a SMIC 0.18 μm CMOS process. Although the power consumption is only 32.1 μW under a 3 V voltage supply, test results show that the chip can successfully extract biopotential signals.

  6. Analog CMOS design for optical coherence tomography signal detection and processing.

    PubMed

    Xu, Wei; Mathine, David L; Barton, Jennifer K

    2008-02-01

    A CMOS circuit was designed and fabricated for optical coherence tomography (OCT) signal detection and processing. The circuit includes a photoreceiver, differential gain stage and lock-in amplifier based demodulator. The photoreceiver consists of a CMOS photodetector and low noise differential transimpedance amplifier which converts the optical interference signal into a voltage. The differential gain stage further amplifies the signal. The in-phase and quadrature channels of the lock-in amplifier each include an analog mixer and switched-capacitor low-pass filter with an external mixer reference signal. The interferogram envelope and phase can be extracted with this configuration, enabling Doppler OCT measurements. A sensitivity of -80 dB is achieved with faithful reproduction of the interferometric signal envelope. A sample image of finger tip is presented.

  7. Bisubstrate analog probes for the insulin receptor protein tyrosine kinase: molecular yardsticks for analyzing catalytic mechanism and inhibitor design.

    PubMed

    Hines, Aliya C; Parang, Keykavous; Kohanski, Ronald A; Hubbard, Stevan R; Cole, Philip A

    2005-08-01

    Bisubstrate analogs have the potential to provide enhanced specificity for protein kinase inhibition and tools to understand catalytic mechanism. Previous efforts led to the design of a peptide-ATP conjugate bisubstrate analog utilizing aminophenylalanine in place of tyrosine and a thioacetyl linker to the gamma-phosphate of ATP which was a potent inhibitor of the insulin receptor kinase (IRK). In this study, we have examined the contributions of various electrostatic and structural elements in the bisubstrate analog to IRK binding affinity. Three types of changes (seven specific analogs in all) were introduced: a Tyr isostere of the previous aminophenylalanine moiety, modifications of the spacer between the adenine and the peptide, and deletions and substitutions within the peptide moiety. These studies allowed a direct evaluation of the hydrogen bond strength between the anilino nitrogen of the bisubstrate analog and the enzyme catalytic base Asp and showed that it contributes 2.5 kcal/mol of binding energy, in good agreement with previous predictions. Modifications of the linker length resulted in weakened inhibitory affinity, consistent with the geometric requirements of an enzyme-catalyzed dissociative transition state. Alterations in the peptide motif generally led to diminished inhibitory potency, and only some of these effects could be rationalized based on prior kinetic and structural studies. Taken together, these results suggest that a combination of mechanism-based design and empirical synthetic manipulation will be necessary in producing optimized protein kinase bisubstrate analog inhibitors.

  8. Expediting analog design retargeting by design knowledge re-use and circuit synthesis: a practical example on a Delta-Sigma modulator

    NASA Astrophysics Data System (ADS)

    Webb, Matthew; Tang, Hua

    2016-08-01

    In the past decade or two, due to constant and rapid technology changes, analog design re-use or design retargeting to newer technologies has been brought to the table in order to expedite the design process and improve time-to-market. If properly conducted, analog design retargeting could significantly cut down design cycle compared to designs starting from the scratch. In this article, we present an empirical and general method for efficient analog design retargeting by design knowledge re-use and circuit synthesis (CS). The method first identifies circuit blocks that compose the source system and extracts the performance parameter specifications of each circuit block. Then, for each circuit block, it scales the values of design variables (DV) from the source design to derive an initial design in the target technology. Depending on the performance of this initial target design, a design space is defined for synthesis. Subsequently, each circuit block is automatically synthesised using state-of-art analog synthesis tools based on a combination of global and local optimisation techniques to achieve comparable performance specifications to those extracted from the source system. Finally, the overall system is composed of those synthesised circuit blocks in the target technology. We illustrate the method using a practical example of a complex Delta-Sigma modulator (DSM) circuit.

  9. Design of novel melatonin analogs for the reduction of intraocular pressure in normotensive rabbits.

    PubMed

    Alarma-Estrany, Pilar; Guzman-Aranguez, Ana; Huete, Fernando; Peral, Assumpta; Plourde, Robert; Pelaez, Teresa; Yerxa, Benjamin; Pintor, Jesús

    2011-06-01

    Melatonin, the MT(2) melatonin receptor agonist IIK7 [N-butanoyl-2-(2-methoxy-6H-isoindolo[2,1-a]indol-11-yl)ethanamine], and the putative MT(3) melatonin receptor agonist 5-MCA-NAT [5-methoxycarbonylamino-N-acetyltryptamine] have previously been shown to reduce intraocular pressure (IOP) in ocular normotensive rabbits. To gain a better understanding of the structure-activity relationship of compounds that activate MT(2) and MT(3) receptors mediating reductions in IOP, novel melatonin analogs with rationally varied substitutions were synthesized and tested for their effects on IOP in ocular normotensive rabbits (n = 160). All synthesized melatonin analogs reduced IOP. The best-effect lowering IOP was obtained with the analogs INS48848 [methyl-1-methylene-2,3,4,9-tetrahydro-1H-carbazol-6-ylcarbamate], INS48862 [methyl-2-bromo-3-(2-ethanamidoethyl)-1H-indol-5-ylcarbamate], and INS48852 [(E)-N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-3-phenylprop-2-enamide]. These compounds produced dose-dependent decreases in IOP that were maximal at 0.1 mM (total dose of 0.259 μg for INS48848, 0.354 μg for INS48862, and 0.320 μg for INS48852) and 1 mM (total dose of 2.59 μg for INS48848, 3.54 μg for INS48862, and 3.20 μg for INS48852), with maximal reductions of 36.0 ± 4.0, 24.0 ± 1.5, and 30.0 ± 1.5% for INS48848, INS48862, and INS48852, respectively. Studies using melatonin receptor antagonists (luzindole, prazosin, and DH97 [N-pentanoyl-2-benzyltryptamine]) indicated that INS48862 and INS48852 activate preferentially a MT(2) melatonin receptor and suggest that INS48848 may act mainly via a MT(3) receptor. The most effective compounds were also well tolerated in a battery of standard ocular surface irritation studies. The implication of these findings to the design of novel drugs to treat ocular hypertension is discussed.

  10. Design of a high linearity and high gain accuracy analog baseband circuit for DAB receiver

    NASA Astrophysics Data System (ADS)

    Li, Ma; Zhigong, Wang; Jian, Xu; Yiqiang, Wu; Junliang, Wang; Mi, Tian; Jianping, Chen

    2015-02-01

    An analog baseband circuit of high linearity and high gain accuracy for a digital audio broadcasting receiver is implemented in a 0.18-μm RFCMOS process. The circuit comprises a 3rd-order active-RC complex filter (CF) and a programmable gain amplifier (PGA). An automatic tuning circuit is also designed to tune the CF's pass band. Instead of the class-A fully differential operational amplifier (FDOPA) adopted in the conventional CF and PGA design, a class-AB FDOPA is specially employed in this circuit to achieve a higher linearity and gain accuracy for its large current swing capability with lower static current consumption. In the PGA circuit, a novel DC offset cancellation technique based on the MOS resistor is introduced to reduce the settling time significantly. A reformative switching network is proposed, which can eliminate the switch resistor's influence on the gain accuracy of the PGA. The measurement result shows the gain range of the circuit is 10-50 dB with a 1-dB step size, and the gain accuracy is less than ±0.3 dB. The OIP3 is 23.3 dBm at the gain of 10 dB. Simulation results show that the settling time is reduced from 100 to 1 ms. The image band rejection is about 40 dB. It only draws 4.5 mA current from a 1.8 V supply voltage.

  11. Structure-guided inhibitor design expands the scope of analog-sensitive kinase technology.

    PubMed

    Zhang, Chao; Lopez, Michael S; Dar, Arvin C; Ladow, Eva; Finkbeiner, Steven; Yun, Cai-Hong; Eck, Michael J; Shokat, Kevan M

    2013-09-20

    Engineered analog-sensitive (AS) protein kinases have emerged as powerful tools for dissecting phospho-signaling pathways, for elucidating the cellular function of individual kinases, and for deciphering unanticipated effects of clinical therapeutics. A crucial and necessary feature of this technology is a bioorthogonal small molecule that is innocuous toward native cellular systems but potently inhibits the engineered kinase. In order to generalize this method, we sought a molecule capable of targeting divergent AS-kinases. Here we employ X-ray crystallography and medicinal chemistry to unravel the mechanism of current inhibitors and use these insights to design the most potent, selective, and general AS-kinase inhibitors reported to date. We use large-scale kinase inhibitor profiling to characterize the selectivity of these molecules as well as examine the consequences of potential off-target effects in chemical genetic experiments. The molecules reported here will serve as powerful tools in efforts to extend AS-kinase technology to the entire kinome and the principles discovered may help in the design of other engineered enzyme/ligand pairs.

  12. Design of a VLSI charge-coupled device analog delay line

    NASA Astrophysics Data System (ADS)

    Gedra, David R.

    1995-03-01

    Charge coupled devices (CCD's) are semiconductor devices which can transfer information, represented by a quantity of electrical charge, from one physical location of the semiconductor substrate to another in a controlled manner with the use of properly sequenced clock pulses. These devices can be applied to imaging, signal processing, logic, and digital storage applications. In this thesis, the design of an electrically stimulated CCD analog delay line, using the design tools currently available at the Naval Postgraduate School, is reported on. The major issues addressed are the electrode gate structure and composition, charge confinement techniques, and clocking schemes. Additionally, techniques for inpuning and detecting charge packets from the CCD register are examined. The Metal Oxide Semiconductor Integration Service (MOSIS) design rules only permit Bulk Channel Charge Couple Devices (BCCD's) to be lald out, and not Surface Channel Charge Coupled Devices (SCCD's). Restricted to a die size of 2.24 mm length, the electrode gates were chosen to be polysilicon polysilicon 8 micron length with 2 micron overlap and 20 micron width, giving the BCCD 64 stages. An on chip four phase clocking circuit with output drivers on each phase provides the control voltage for the gate electrodes. The small width of the BCCD delay line utilizes only a small portion of the available 2.22 mm die width. Therefore, four different BCCD's were designed in the layout. Two of the BCCD's have a p-diffusion stop to contain the charge laterally as it propagates along the channel while two BCCD's do not. Additionally, two of the BCCD's utilize the charge partition input technique with three control gates and two BCCD's use the dynamic current injection with one control gate.

  13. Design, Synthesis, Biological Evaluation and Docking Studies of Pterostilbene Analogs Inside PPARa

    USDA-ARS?s Scientific Manuscript database

    Pterostilbene, a naturally occurring analog of resveratrol, has previously shown PPARa activation in H4IIEC3 cells and was found to decrease cholesterol levels in animals. In this study, analogs of pterostilbene were synthesized and their ability to activate PPARa was investigated. Among the analo...

  14. The Role of Analogical Thinking in Designing Tasks for Mathematics Teacher Education: An Example of a Pedagogical Ad Hoc Task

    ERIC Educational Resources Information Center

    Peled, Irit

    2007-01-01

    This article discusses the design of tasks for teacher education. It focuses on tasks that are used in a university course for pre-service secondary school mathematics teachers. Special attention is given to tasks that use analogical thinking in their construction or implementation. These tasks are categorized by type of teacher education goal and…

  15. Methodological Issues in Analog Acceptability Research: Are Teachers' Acceptability Ratings of Assessment Methods Influenced by Experimental Design?

    ERIC Educational Resources Information Center

    Eckert, Tanya L.; Shapiro, Edward S.

    1999-01-01

    Explores the relationship between experimental design method and teacher-rated acceptability of two analog approaches for assessing academic skills problems. Comparisons indicate that curriculum-based assessment was consistently rated as a more acceptable method of assessment than published, norm-referenced tests. Results are discussed in relation…

  16. The Solar Probe Plus Radio Frequency Spectrometer: Measurement requirements, analog design, and digital signal processing

    NASA Astrophysics Data System (ADS)

    Pulupa, M.; Bale, S. D.; Bonnell, J. W.; Bowen, T. A.; Carruth, N.; Goetz, K.; Gordon, D.; Harvey, P. R.; Maksimovic, M.; Martínez-Oliveros, J. C.; Moncuquet, M.; Saint-Hilaire, P.; Seitz, D.; Sundkvist, D.

    2017-03-01

    The Radio Frequency Spectrometer (RFS) is a two-channel digital receiver and spectrometer, which will make remote sensing observations of radio waves and in situ measurements of electrostatic and electromagnetic fluctuations in the solar wind. A part of the FIELDS suite for Solar Probe Plus (SPP), the RFS is optimized for measurements in the inner heliosphere, where solar radio bursts are more intense and the plasma frequency is higher compared to previous measurements at distances of 1 AU or greater. The inputs to the RFS receiver are the four electric antennas mounted near the front of the SPP spacecraft and a single axis of the SPP search coil magnetometer (SCM). Each RFS channel selects a monopole or dipole antenna input, or the SCM input, via multiplexers. The primary data products from the RFS are autospectra and cross spectra from the selected inputs. The spectra are calculated using a polyphase filter bank, which enables the measurement of low amplitude signals of interest in the presence of high-amplitude narrowband noise generated by spacecraft systems. We discuss the science signals of interest driving the RFS measurement objectives, describe the RFS analog design and digital signal processing, and show examples of current performance.

  17. Design and analysis of a dual mode CMOS field programmable analog array

    NASA Astrophysics Data System (ADS)

    Xiaoyan, Cheng; Haigang, Yang; Tao, Yin; Qisong, Wu; Hongfeng, Zhang; Fei, Liu

    2014-10-01

    This paper presents a novel field-programmable analog array (FPAA) architecture featuring a dual mode including discrete-time (DT) and continuous-time (CT) operation modes, along with a highly routable connection boxes (CBs) based interconnection lattice. The dual mode circuit for the FPAA is capable of achieving targeted optimal performance in different applications. The architecture utilizes routing switches in a CB not only for the signal interconnection purpose but also for control of the electrical charge transfer required in switched-capacitor circuits. This way, the performance of the circuit in either mode shall not be hampered with adding of programmability. The proposed FPAA is designed and implemented in a 0.18 μm standard CMOS process with a 3.3 V supply voltage. The result from post-layout simulation shows that a maximum bandwidth of 265 MHz through the interconnection network is achieved. The measured results from demonstrated examples show that the maximum signal bandwidth of up to 2 MHz in CT mode is obtained with the spurious free dynamic range of 54 dB, while the signal processing precision in DT mode reaches 96.4%.

  18. Centrally truncated and stabilized porcine neuropeptide Y analogs: design, synthesis, and mouse brain receptor binding.

    PubMed Central

    Krstenansky, J L; Owen, T J; Buck, S H; Hagaman, K A; McLean, L R

    1989-01-01

    Porcine neuropeptide Y (pNPY) has been proposed to form an intramolecularly stabilized structure characterized by N- and C-terminal helical regions arranged antiparallel due to a central turn region. Analogs based on this structural model that have the central turn region and various amounts of the helical regions removed, yet retain the N and C termini in a similar spatial orientation were designed. The gap formed by removal of the central residues (residues 8-17 or 7-20) was spanned with a single 8-aminooctanoic acid residue (Aoc) and the structure was further stabilized by the introduction of a disulfide bridge. [D-Cys7,Aoc8-17,Cys20]pNPY and [Cys5,Aoc7-20,D-Cys24]pNPY were synthesized and found to have receptor binding affinities of 2.3 nM and 150 nM, respectively, in mouse brain membranes (pNPY affinity is 3.6 nM in this assay). It is proposed that the central region (residues 7-17) of pNPY serves a structural role in the peptide and is not involved in direct receptor interaction. PMID:2543973

  19. Toward Smart Aerospace Structures: Design of a Piezoelectric Sensor and Its Analog Interface for Flaw Detection

    PubMed Central

    Boukabache, Hamza; Escriba, Christophe; Fourniols, Jean-Yves

    2014-01-01

    Structural health monitoring using noninvasive methods is one of the major challenges that aerospace manufacturers face in this decade. Our work in this field focuses on the development and the system integration of millimetric piezoelectric sensors/ actuators to generate and measure specific guided waves. The aim of the application is to detect mechanical flaws on complex composite and alloy structures to quantify efficiently the global structures' reliability. The study begins by a physical and analytical analysis of a piezoelectric patch. To preserve the structure's integrity, the transducers are directly pasted onto the surface which leads to a critical issue concerning the interfacing layer. In order to improve the reliability and mitigate the influence of the interfacing layer, the global equations of piezoelectricity are coupled with a load transfer model. Thus we can determine precisely the shear strain developed on the surface of the structure. To exploit the generated signal, a high precision analog charge amplifier coupled to a double T notch filter were designed and scaled. Finally, a novel joined time-frequency analysis based on a wavelet decomposition algorithm is used to extract relevant structures signatures. Finally, this paper provides examples of application on aircraft structure specimens and the feasibility of the system is thus demonstrated. PMID:25365457

  20. Toward smart aerospace structures: design of a piezoelectric sensor and its analog interface for flaw detection.

    PubMed

    Boukabache, Hamza; Escriba, Christophe; Fourniols, Jean-Yves

    2014-10-31

    Structural health monitoring using noninvasive methods is one of the major challenges that aerospace manufacturers face in this decade. Our work in this field focuses on the development and the system integration of millimetric piezoelectric sensors/ actuators to generate and measure specific guided waves. The aim of the application is to detect mechanical flaws on complex composite and alloy structures to quantify efficiently the global structures' reliability. The study begins by a physical and analytical analysis of a piezoelectric patch. To preserve the structure's integrity, the transducers are directly pasted onto the surface which leads to a critical issue concerning the interfacing layer. In order to improve the reliability and mitigate the influence of the interfacing layer, the global equations of piezoelectricity are coupled with a load transfer model. Thus we can determine precisely the shear strain developed on the surface of the structure. To exploit the generated signal, a high precision analog charge amplifier coupled to a double T notch filter were designed and scaled. Finally, a novel joined time-frequency analysis based on a wavelet decomposition algorithm is used to extract relevant structures signatures. Finally, this paper provides examples of application on aircraft structure specimens and the feasibility of the system is thus demonstrated.

  1. Fiber-lattice accumulator design considerations for optical sigma delta analog-to-digital converters

    NASA Astrophysics Data System (ADS)

    Pace, Phillip E.; Bewley, S. A.; Powers, John P.

    2000-06-01

    Integrated optical sigma-delta ((Sigma) (Delta) ) analog-to- digital converters (ADCs) use a pulsed laser to oversample an input signal at two Mach-Zehnder interferometers. A fiber-lattice accumulator is embedded within a feedback loop around a single-bit quantizer to spectrally shape the quantization noise to fall outside the signal band of interest. Decimation filtering is applied to the quantizer output to construct the input signal with high resolution. Applications of integrated optical (Sigma) (Delta) ADCs include digitizing wideband radio-frequency signals directly at an antenna (digital antenna). In this paper, a novel fiber- lattice accumulator design is presented, and a coherent simulation of an integrated optical first-order, single-bit (Sigma) (Delta) ADC is reported. The accumulator leakage resulting from a mismatch in the optical circuit parameters is quantified. A time-domain analysis is presented, and the simulation results from an all-electronic (Sigma) (Delta) ADC are presented for comparison. A frequency-domain analysis of a ten times oversampling (n equals 4 bits) simulation is used to compare the dynamic performance parameters, including the spurious-free dynamic range, signal-to-noise-plus-distortion ratio, and effective number of bits. The formation of image frequencies when the accumulator is overloaded (i.e., the optical amplifier gain is too large) is also investigated.

  2. A novel model system for design of biomaterials based on recombinant analogs of spider silk proteins.

    PubMed

    Bogush, Vladimir G; Sokolova, Olga S; Davydova, Lyubov I; Klinov, Dmitri V; Sidoruk, Konstantin V; Esipova, Natalya G; Neretina, Tatyana V; Orchanskyi, Igor A; Makeev, Vsevolod Yu; Tumanyan, Vladimir G; Shaitan, Konstantin V; Debabov, Vladimir G; Kirpichnikov, Mikhail P

    2009-03-01

    Spider dragline silk possesses impressive mechanical and biochemical properties. It is synthesized by a couple of major ampullate glands in spiders and comprises of two major structural proteins--spidroins 1 and 2. The relationship between structure and mechanical properties of spider silk is not well understood. Here, we modeled the complete process of the spider silk assembly using two new recombinant analogs of spidroins 1 and 2. The artificial genes sequence of the hydrophobic core regions of spidroin 1 and 2 have been designed using computer analysis of existing databases and mathematical modeling. Both proteins were expressed in Pichia pastoris and purified using a cation exchange chromatography. Despite the absence of hydrophilic N- and C-termini, both purified proteins spontaneously formed the nanofibrils and round micelles of about 1 microm in aqueous solutions. The electron microscopy study has revealed the helical structure of a nanofibril with a repeating motif of 40 nm. Using the electrospinning, the thin films with an antiparallel beta-sheet structure were produced. In summary, we were able to obtain artificial structures with characteristics that are perspective for further biomedical applications, such as producing three-dimensional matrices for tissue engineering and drug delivery.

  3. Design, synthesis and characterization of a highly effective inhibitor for analog-sensitive (as) kinases.

    PubMed

    Klein, Michael; Morillas, Montse; Vendrell, Alexandre; Brive, Lars; Gebbia, Marinella; Wallace, Iain M; Giaever, Guri; Nislow, Corey; Posas, Francesc; Grøtli, Morten

    2011-01-01

    Highly selective, cell-permeable and fast-acting inhibitors of individual kinases are sought-after as tools for studying the cellular function of kinases in real time. A combination of small molecule synthesis and protein mutagenesis, identified a highly potent inhibitor (1-Isopropyl-3-(phenylethynyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine) of a rationally engineered Hog1 serine/threonine kinase (Hog1(T100G)). This inhibitor has been successfully used to study various aspects of Hog1 signaling, including a transient cell cycle arrest and gene expression changes mediated by Hog1 in response to stress. This study also underscores that the general applicability of this approach depends, in part, on the selectivity of the designed the inhibitor with respect to activity versus the engineered and wild type kinases. To explore this specificity in detail, we used a validated chemogenetic assay to assess the effect of this inhibitor on all gene products in yeast in parallel. The results from this screen emphasize the need for caution and for case-by-case assessment when using the Analog-Sensitive Kinase Allele technology to assess the physiological roles of kinases.

  4. Halogenated analogs of 1'-acetoxychavicol acetate, Rev-export inhibitor from Alpinia galanga, designed from mechanism of action.

    PubMed

    Tamura, Satoru; Shiomi, Atsushi; Kimura, Tominori; Murakami, Nobutoshi

    2010-04-01

    In the course of search for the robust analogs of 1'-acetoxychavicol acetate (ACA, 1), the Rev-export inhibitor from the medicinal plant Alpinia galanga, we clarified formation of the quinone methide intermediate ii to be essential for exerting the inhibitory activity of 1. Based on this mechanism of action, the rational design from the MO calculation of the conclusive activation energy to ii resulted in the four halogenated analogs with more potent activity than ACA (1). In particular, the difluoroanalog 20d exhibited approximately four-fold potent activity as compared with 1. 2010 Elsevier Ltd. All rights reserved.

  5. Analog series-based scaffolds: computational design and exploration of a new type of molecular scaffolds for medicinal chemistry

    PubMed Central

    Dimova, Dilyana; Stumpfe, Dagmar; Hu, Ye; Bajorath, Jürgen

    2016-01-01

    Aim: Computational design of and systematic search for a new type of molecular scaffolds termed analog series-based scaffolds. Materials & methods: From currently available bioactive compounds, analog series were systematically extracted, key compounds identified and new scaffolds isolated from them. Results: Using our computational approach, more than 12,000 scaffolds were extracted from bioactive compounds. Conclusion: A new scaffold definition is introduced and a computational methodology developed to systematically identify such scaffolds, yielding a large freely available scaffold knowledge base. PMID:28116132

  6. PRACA Enhancement Pilot Study Report: Engineering for Complex Systems Program (formerly Design for Safety), DFS-IC-0006

    NASA Technical Reports Server (NTRS)

    Korsmeyer, David; Schreiner, John

    2002-01-01

    This technology evaluation report documents the findings and recommendations of the Engineering for Complex Systems Program (formerly Design for Safety) PRACA Enhancement Pilot Study of the Space Shuttle Program's (SSP's) Problem Reporting and Corrective Action (PRACA) System. A team at NASA Ames Research Center (ARC) performed this Study. This Study was initiated as a follow-on to the NASA chartered Shuttle Independent Assessment Team (SIAT) review (performed in the Fall of 1999) which identified deficiencies in the current PRACA implementation. The Pilot Study was launched with an initial qualitative assessment and technical review performed during January 2000 with the quantitative formal Study (the subject of this report) started in March 2000. The goal of the PRACA Enhancement Pilot Study is to evaluate and quantify the technical aspects of the SSP PRACA systems and recommend enhancements to address deficiencies and in preparation for future system upgrades.

  7. Experimental Evaluation of Incorporating Digital and Analog Integrated Circuit Die on a Common Substrate Utilizing Silicon-Hybrid Wafer-Scale Integration Technology

    DTIC Science & Technology

    1992-03-01

    potential impact on analog signals compared to digital signals. These measurements were used to evaluate the effectiveness of the WSI techniques in...simply increasing the overall size of a particular IC design, factors of yield and cost effectiveness represent significant barriers (40:23). When...the wafer and packaged for use. Cost effective yields are routinely achieved for these smaller IC die. One simple model of IC die yield predicts an

  8. Short KR-12 analogs designed from human cathelicidin LL-37 possessing both antimicrobial and antiendotoxic activities without mammalian cell toxicity.

    PubMed

    Jacob, Binu; Park, Il-Seon; Bang, Jeong-Kyu; Shin, Song Yub

    2013-11-01

    KR-12 (residues 18-29 of LL-37) was known to be the smallest peptide of human cathelicidin LL-37 possessing antimicrobial activity. In order to optimize α-helical short antimicrobial peptides having both antimicrobial and antiendotoxic activities without mammalian cell toxicity, we designed and synthesized a series of KR-12 analogs. Highest hydrophobic analogs KR-12-a5 and KR-12-a6 displayed greater inhibition of lipopolysaccharide (LPS)-stimulated tumor necrosis factor-α production and higher LPS-binding activity. We have observed that antimicrobial activity is independent of charge, but LPS neutralization requires a balance of hydrophobicity and net positive charge. Among KR-12 analogs, KR-12-a2, KR-12-a3 and KR-12-a4 showed much higher cell specificity for bacteria over erythrocytes and retained antiendotoxic activity, relative to parental LL-37. KR-12-a5 displayed the strongest antiendotoxic activity but almost similar cell specificity as compared with LL-37. Also, these KR-12 analogs (KR-12-a2, KR-12-a3, KR-12-a4 and KR-12-a5) exhibited potent antimicrobial activity (minimal inhibitory concentration: 4 μM) against methicillin-resistant Staphylococcus aureus. Taken together, these KR-12 analogs have the potential for future development as a novel class of antimicrobial and anti-inflammatory therapeutic agents. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.

  9. Design, synthesis and biological evaluation of dinucleotide mRNA cap analog containing propargyl moiety.

    PubMed

    Shanmugasundaram, Muthian; Charles, Irudaya; Kore, Anilkumar R

    2016-03-15

    The first example of the synthesis of new dinucleotide cap analog containing propargyl group such as m(7,3'-O-propargyl)G[5']ppp[5']G is reported. The effect of propargyl cap analog with standard cap was evaluated with respect to their capping efficiency, in vitro T7 RNA polymerase transcription efficiency, and translation activity using cultured HeLa cells. It is noteworthy that propargyl cap analog outperforms standard cap by 3.1 fold in terms of translational properties. The propargyl cap analog forms a more stable complex with translation initiation factor eIF4E based on the molecular modeling studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Analog design optimization methodology for ultralow-power circuits using intuitive inversion-level and saturation-level parameters

    NASA Astrophysics Data System (ADS)

    Eimori, Takahisa; Anami, Kenji; Yoshimatsu, Norifumi; Hasebe, Tetsuya; Murakami, Kazuaki

    2014-01-01

    A comprehensive design optimization methodology using intuitive nondimensional parameters of inversion-level and saturation-level is proposed, especially for ultralow-power, low-voltage, and high-performance analog circuits with mixed strong, moderate, and weak inversion metal-oxide-semiconductor transistor (MOST) operations. This methodology is based on the synthesized charge-based MOST model composed of Enz-Krummenacher-Vittoz (EKV) basic concepts and advanced-compact-model (ACM) physics-based equations. The key concept of this methodology is that all circuit and system characteristics are described as some multivariate functions of inversion-level parameters, where the inversion level is used as an independent variable representative of each MOST. The analog circuit design starts from the first step of inversion-level design using universal characteristics expressed by circuit currents and inversion-level parameters without process-dependent parameters, followed by the second step of foundry-process-dependent design and the last step of verification using saturation-level criteria. This methodology also paves the way to an intuitive and comprehensive design approach for many kinds of analog circuit specifications by optimization using inversion-level log-scale diagrams and saturation-level criteria. In this paper, we introduce an example of our design methodology for a two-stage Miller amplifier.

  11. Rational design of hetero-ring-expanded guanine analogs with enhanced properties for modified DNA building blocks.

    PubMed

    Zhang, Jinmei; Cukier, Robert I; Bu, Yuxiang

    2007-07-19

    The properties and modes of recognition of physiological DNAs associated with the four natural nucleobases might be extended, in principle, by the design of non-natural nucleobase derivatives. The goal is an expansion of the genetic alphabet, with the possible outcome of producing new DNAs with improved physical or biological properties. In this work, a new series of hetero-ring-expanded guanine analogs are proposed, and their relevant structural characteristics and electronic properties are determined by density functional theory. The stabilities of the decamer DNA duplexes (dn.dC)10 (where n represents the corresponding expanded guanine analog designed here) are also examined, using molecular dynamics. The simulations show that the designed motifs can form stable DNA-like structures. We determined the pairing energies for the Watson-Crick (WC) hydrogen-bonded dimers between the expanded G-analogs and the natural C, and found that the pairing energies are close to those of the natural GC pair. The calculated adiabatic ionization potentials (IPs) of the size-expanded guanine analogs and their base pairs, and the corresponding vertical ionization potentials, show that some are distinctly smaller than the corresponding natural versions. The HOMO-LUMO energy gaps for most of the size-expanded guanine analogs and their WC base pairs are considerably lower than those of the corresponding natural base and base pairs. Thus, the expanded G bases may be considered as DNA genetic motifs, and they may serve as building blocks for potential biological applications and the development of molecular electronic devices.

  12. Structural analyses of covalent enzyme-substrate analog complexes reveal strengths and limitations of de novo enzyme design.

    PubMed

    Wang, Ling; Althoff, Eric A; Bolduc, Jill; Jiang, Lin; Moody, James; Lassila, Jonathan K; Giger, Lars; Hilvert, Donald; Stoddard, Barry; Baker, David

    2012-01-20

    We report the cocrystal structures of a computationally designed and experimentally optimized retro-aldol enzyme with covalently bound substrate analogs. The structure with a covalently bound mechanism-based inhibitor is similar to, but not identical with, the design model, with an RMSD of 1.4 Å over active-site residues and equivalent substrate atoms. As in the design model, the binding pocket orients the substrate through hydrophobic interactions with the naphthyl moiety such that the oxygen atoms analogous to the carbinolamine and β-hydroxyl oxygens are positioned near a network of bound waters. However, there are differences between the design model and the structure: the orientation of the naphthyl group and the conformation of the catalytic lysine are slightly different; the bound water network appears to be more extensive; and the bound substrate analog exhibits more conformational heterogeneity than typical native enzyme-inhibitor complexes. Alanine scanning of the active-site residues shows that both the catalytic lysine and the residues around the binding pocket for the substrate naphthyl group make critical contributions to catalysis. Mutating the set of water-coordinating residues also significantly reduces catalytic activity. The crystal structure of the enzyme with a smaller substrate analog that lacks naphthyl ring shows the catalytic lysine to be more flexible than in the naphthyl-substrate complex; increased preorganization of the active site would likely improve catalysis. The covalently bound complex structures and mutagenesis data highlight the strengths and weaknesses of the de novo enzyme design strategy. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. The development and demonstration of hybrid programmable attitude control electronics. [with adaptable analog/digital design approach

    NASA Technical Reports Server (NTRS)

    Smith, L. S.; Kopf, E. H., Jr.

    1974-01-01

    HYPACE provides an adaptable, analog/digital design approach that permits preflight and in-flight accommodation of mission changes, component performance variations, spacecraft changes, etc., through programing. This enabled broad multimission flexibility of application in a cost-effective manner. The HYPACE design, which was demonstrated in breadboard form on a single-axis gas-bearing spacecraft simulation, uses a single control channel to perform the attitude control functions sequentially, thus significantly reducing the number of component parts over hard-wired designs. The success of this effort resulted in the concept being selected for the Mariner/Jupiter/Saturn 1977 spacecraft application.

  14. The development and demonstration of hybrid programmable attitude control electronics. [with adaptable analog/digital design approach

    NASA Technical Reports Server (NTRS)

    Smith, L. S.; Kopf, E. H., Jr.

    1974-01-01

    HYPACE provides an adaptable, analog/digital design approach that permits preflight and in-flight accommodation of mission changes, component performance variations, spacecraft changes, etc., through programing. This enabled broad multimission flexibility of application in a cost-effective manner. The HYPACE design, which was demonstrated in breadboard form on a single-axis gas-bearing spacecraft simulation, uses a single control channel to perform the attitude control functions sequentially, thus significantly reducing the number of component parts over hard-wired designs. The success of this effort resulted in the concept being selected for the Mariner/Jupiter/Saturn 1977 spacecraft application.

  15. IC: Frequently Asked Questions

    MedlinePlus

    ... Resources My Profile Login Social Media Twitter YouTube Facebook Pinterest Community ShareThis Google Search Toggle navigation Menu ... ICA’s Online Support Community Virtual Patient Education IC Facebook Community Voices of Hope Blog ICA Support Group ...

  16. IC Treatment: Antidepressants

    MedlinePlus

    ... Resources My Profile Login Social Media Twitter YouTube Facebook Pinterest Community ShareThis Google Search Toggle navigation Menu ... ICA’s Online Support Community Virtual Patient Education IC Facebook Community Voices of Hope Blog ICA Support Group ...

  17. IC Treatment: Surgical Procedures

    MedlinePlus

    ... Resources My Profile Login Social Media Twitter YouTube Facebook Pinterest Community ShareThis Google Search Toggle navigation Menu ... ICA’s Online Support Community Virtual Patient Education IC Facebook Community Voices of Hope Blog ICA Support Group ...

  18. Men and IC

    MedlinePlus

    ... Resources My Profile Login Social Media Twitter YouTube Facebook Pinterest Community ShareThis Google Search Toggle navigation Menu ... ICA’s Online Support Community Virtual Patient Education IC Facebook Community Voices of Hope Blog ICA Support Group ...

  19. General IC Symptoms

    MedlinePlus

    ... Resources My Profile Login Social Media Twitter YouTube Facebook Pinterest Community ShareThis Google Search Toggle navigation Menu ... ICA’s Online Support Community Virtual Patient Education IC Facebook Community Voices of Hope Blog ICA Support Group ...

  20. Children and IC

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  1. IC Associated Conditions

    MedlinePlus

    ... Pain Complementary Therapies Complementary vs. Alternative Herbs, Dietary Supplements, & Biologicals Mind-body Medicine Massage, Manipulation, & Body-based Practices Energy Medicine Bringing Treatments to Market IC Healthcare Provider ...

  2. Pregnancy and IC

    MedlinePlus

    ... Pain Complementary Therapies Complementary vs. Alternative Herbs, Dietary Supplements, & Biologicals Mind-body Medicine Massage, Manipulation, & Body-based Practices Energy Medicine Bringing Treatments to Market IC Healthcare Provider ...

  3. Children and IC

    MedlinePlus

    ... Pain Complementary Therapies Complementary vs. Alternative Herbs, Dietary Supplements, & Biologicals Mind-body Medicine Massage, Manipulation, & Body-based Practices Energy Medicine Bringing Treatments to Market IC Healthcare Provider ...

  4. Men and IC

    MedlinePlus

    ... Pain Complementary Therapies Complementary vs. Alternative Herbs, Dietary Supplements, & Biologicals Mind-body Medicine Massage, Manipulation, & Body-based Practices Energy Medicine Bringing Treatments to Market IC Healthcare Provider ...

  5. General IC Symptoms

    MedlinePlus

    ... Pain Complementary Therapies Complementary vs. Alternative Herbs, Dietary Supplements, & Biologicals Mind-body Medicine Massage, Manipulation, & Body-based Practices Energy Medicine Bringing Treatments to Market IC Healthcare Provider ...

  6. IC: Frequently Asked Questions

    MedlinePlus

    ... Pain Complementary Therapies Complementary vs. Alternative Herbs, Dietary Supplements, & Biologicals Mind-body Medicine Massage, Manipulation, & Body-based Practices Energy Medicine Bringing Treatments to Market IC Healthcare Provider ...

  7. IC Treatment: Antidepressants

    MedlinePlus

    ... Pain Complementary Therapies Complementary vs. Alternative Herbs, Dietary Supplements, & Biologicals Mind-body Medicine Massage, Manipulation, & Body-based Practices Energy Medicine Bringing Treatments to Market IC Healthcare Provider ...

  8. IC Treatment: Surgical Procedures

    MedlinePlus

    ... Pain Complementary Therapies Complementary vs. Alternative Herbs, Dietary Supplements, & Biologicals Mind-body Medicine Massage, Manipulation, & Body-based Practices Energy Medicine Bringing Treatments to Market IC Healthcare Provider ...

  9. IC Treatment: Antihistamines

    MedlinePlus

    ... Pain Complementary Therapies Complementary vs. Alternative Herbs, Dietary Supplements, & Biologicals Mind-body Medicine Massage, Manipulation, & Body-based Practices Energy Medicine Bringing Treatments to Market IC Healthcare Provider ...

  10. High performance MPEG-audio decoder IC

    NASA Technical Reports Server (NTRS)

    Thorn, M.; Benbassat, G.; Cyr, K.; Li, S.; Gill, M.; Kam, D.; Walker, K.; Look, P.; Eldridge, C.; Ng, P.

    1993-01-01

    The emerging digital audio and video compression technology brings both an opportunity and a new challenge to IC design. The pervasive application of compression technology to consumer electronics will require high volume, low cost IC's and fast time to market of the prototypes and production units. At the same time, the algorithms used in the compression technology result in complex VLSI IC's. The conflicting challenges of algorithm complexity, low cost, and fast time to market have an impact on device architecture and design methodology. The work presented in this paper is about the design of a dedicated, high precision, Motion Picture Expert Group (MPEG) audio decoder.

  11. High performance MPEG-audio decoder IC

    NASA Technical Reports Server (NTRS)

    Thorn, M.; Benbassat, G.; Cyr, K.; Li, S.; Gill, M.; Kam, D.; Walker, K.; Look, P.; Eldridge, C.; Ng, P.

    1993-01-01

    The emerging digital audio and video compression technology brings both an opportunity and a new challenge to IC design. The pervasive application of compression technology to consumer electronics will require high volume, low cost IC's and fast time to market of the prototypes and production units. At the same time, the algorithms used in the compression technology result in complex VLSI IC's. The conflicting challenges of algorithm complexity, low cost, and fast time to market have an impact on device architecture and design methodology. The work presented in this paper is about the design of a dedicated, high precision, Motion Picture Expert Group (MPEG) audio decoder.

  12. Design and Synthesis of an Inositol Phosphate Analog Based on Computational Docking Studies.

    PubMed

    Peng, Zhenghong; Maxwell, David; Sun, Duoli; Ying, Yunming; Schuber, Paul T; Bhanu Prasad, Basvoju A; Gelovani, Juri; Yung, Wai-Kwan Alfred; Bornmann, William G

    2014-01-28

    A virtual library of 54 inositol analog mimics of In(1,4,5)P3 has been docked, scored, and ranked within the binding site of human inositol 1,4,5-trisphosphate 3-kinase A (IP3-3KA). Chemical synthesis of the best scoring structure that also met distance criteria for 3'-OH to -P in Phosphate has been attempted along with the synthesis of (1S,2R,3S,4S)-3-fluoro-2,4-dihydroxycyclohexanecarboxylic acid as an inositol analog, useful for non-invasive visualization and quantitation of IP3-3KA enzymatic activity.

  13. Design and optimization of an analog filter with a CdTe detector for X-ray fluorescence applications

    NASA Astrophysics Data System (ADS)

    Choi, Hyojeong; Kim, Hui Su; Kim, Young Soo; Ha, Jang Ho; Chai, Jong-Seo

    2016-10-01

    An analog pre-filter circuit for digital pulse processing is designed and optimized for X-ray fluorescence (XRF) applications to replace traditional analog shaping amplifiers. To optimize the pre-filter performance, we characterized noise electrons as a function of the input pulse rise time and decay time of the output pulse by using the full width at half maximum. In addition, gamma-ray energy measurements at room temperature showed that the commercially available CdTe Schottky-type radiation detector with our newly designed and optimized pre-filter circuit exhibited full widths at half maxima of 4.97 (Ba-133, at 53 keV) and 5.56 keV (Am-241, at 59.5 keV), respectively.

  14. Photoactive analogs of farnesyl diphosphate and related isoprenoids: design and applications in studies of medicinally important isoprenoid-utilizing enzymes.

    PubMed

    Vervacke, Jeffrey S; Wang, Yen-Chih; Distefano, Mark D

    2013-01-01

    Farnesyl diphosphate (FPP) is an important metabolic intermediate in the biosynthesis of a variety of molecules including sesquiterpenes and the side chains of a number of cofactors. FPP is also the source of isoprenoid side chains found attached to proteins. Enzymes that employ FPP as a substrate are of interest because they are involved in the semisynthesis of drugs as well as targets for drug design. Photoactive analogs of FPP have been useful for identifying enzymes that use this molecule as a substrate. A variety of photocrosslinking groups have been employed to prepare FPP analogs for use in such experiments including aryl azides, diazotrifluoropropionates and benzophenones. In this review, the design of these probes is described along with an examination of how they have been used in crosslinking experiments.

  15. Design, synthesis, and biophysical properties of a helical Abeta1-42 analog: Inhibition of fibrillogenesis and cytotoxicity.

    PubMed

    Matsuzaki, Katsumi; Okada, Takuma; Tsukuda, Miho; Ikeda, Keisuke; Sohma, Youhei; Chiyomori, Yousuke; Taniguchi, Atsuhiko; Nakamura, Setsuko; Ito, Nui; Hayashi, Yoshio; Kiso, Yoshiaki

    2008-07-11

    The aggregation of amyloid beta-peptide (Abeta) into beta-sheet-rich aggregates is a crucial step in the etiology of Alzheimer's disease. Helical forms of Abeta have been suggested to be intermediates in the aggregation process of the peptide in aqueous phase, micelles and membranes. A stable helical Abeta analog would be useful to investigate the role of helical intermediates in fibrillization by Abeta. Here we designed a helical analog by simply cross-linking the Cys residues of A30C, G37C-Abeta1-42 with 1,6-bismaleimidohexane. The analog assumed a weak alpha-helical conformation in model membranes mimicking lipid raft microdomains of neuronal membranes under conditions in which the wild-type Abeta1-42 formed a beta-sheet, indicating the cross-linking locally induced a helical conformation. Furthermore, addition of equimolar helical Abeta analog significantly reduced the amyloid formation and cytotoxicity by Abeta1-42. Thus, our helical Abeta1-42 is not only a model peptide to investigate the role of helical intermediates in fibrillization by Abeta, but also an inhibitor of Abeta-induced cytotoxicity.

  16. Customized analog circuit design for fiber-based optical coherence microscopy

    NASA Astrophysics Data System (ADS)

    Xu, Wei; Bonnema, Garret T.; Gossage, Kirk W.; Wade, Norman H.; Medford, June; Barton, Jennifer K.

    2006-01-01

    Optical coherence microscopy (OCM) is an interferometric method for acquiring high-resolution, depth-resolved, en face images. In this article we demonstrate a fiber-based OCM system with analog fringe generation and signal demodulation. A high power operational amplifier drives a mirrored piezoelectric stack mounted in the reference arm of the interferometer causing a displacement equal to 0.42 times the light source center wavelength. The drive signal is synchronized with the demodulation frequency of two analog lock-in amplifiers which extract the first and second harmonics of the interferometric component of the signal. Four outputs (X and Y components of first and second harmonics) are acquired with a data-acquisition board and combined to eliminate the slow phase drift in the interferometer. A sample image of carrot tap root is presented. High dynamic range images are obtained at acquisition speeds up to 40000pixels/s.

  17. Design and characterization of α-melanotropin peptide analogs cyclized through rhenium and technetium metal coordination

    PubMed Central

    Giblin, Michael F.; Wang, Nannan; Hoffman, Timothy J.; Jurisson, Silvia S.; Quinn, Thomas P.

    1998-01-01

    α-Melanocyte stimulating hormone (α-MSH) analogs, cyclized through site-specific rhenium (Re) and technetium (Tc) metal coordination, were structurally characterized and analyzed for their abilities to bind α-MSH receptors present on melanoma cells and in tumor-bearing mice. Results from receptor-binding assays conducted with B16 F1 murine melanoma cells indicated that receptor-binding affinity was reduced to approximately 1% of its original levels after Re incorporation into the cyclic Cys4,10, d-Phe7–α-MSH4-13 analog. Structural analysis of the Re–peptide complex showed that the disulfide bond of the original peptide was replaced by thiolate–metal–thiolate cyclization. A comparison of the metal-bound and metal-free structures indicated that metal complexation dramatically altered the structure of the receptor-binding core sequence. Redesign of the metal binding site resulted in a second-generation Re–peptide complex (ReCCMSH) that displayed a receptor-binding affinity of 2.9 nM, 25-fold higher than the initial Re–α-MSH analog. Characterization of the second-generation Re–peptide complex indicated that the peptide was still cyclized through Re coordination, but the structure of the receptor-binding sequence was no longer constrained. The corresponding 99mTc- and 188ReCCMSH complexes were synthesized and shown to be stable in phosphate-buffered saline and to challenges from diethylenetriaminepentaacetic acid (DTPA) and free cysteine. In vivo, the 99mTcCCMSH complex exhibited significant tumor uptake and retention and was effective in imaging melanoma in a murine-tumor model system. Cyclization of α-MSH analogs via 99mTc and 188Re yields chemically stable and biologically active molecules with potential melanoma-imaging and therapeutic properties. PMID:9788997

  18. Pressure generated on a simulated oral analog by impression materials in custom trays of different designs.

    PubMed

    Masri, Radi; Driscoll, Carl F; Burkhardt, John; Von Fraunhofer, Anthony; Romberg, Elaine

    2002-09-01

    To measure the pressure exerted by maxillary edentulous impressions composed of 3 commonly used impression materials using four different impression tray configurations. The study was performed using an oral analog that simulated an edentulous maxillary arch. Three pressure transducers were imbedded in the oral analog, 1 in the mid-palate area and the other 2 in the right and left ridge (maxillary first premolar areas). Custom trays of 4 different configurations were fabricated. The 3 impression materials tested were irreversible hydrocolloid, light-body and medium-body vinyl polysiloxane, and polysulfide. A total of 128 impressions were made. The custom tray and the oral analog were mounted using a reline jig. A Satec universal testing machine was used to apply a constant pressure of 2 kg/cm(2) over a period of 5 minutes on the loaded custom tray. The pressure was recorded every 10 seconds. Factorial analysis of variance and Tukey's multiple comparison test were used to analyze the results. A significant difference in the pressure produced using different impression materials was found (p < or =0.001). Irreversible hydrocolloid and medium-body vinyl polysiloxane produced a significantly higher pressure than light-body vinyl polysiloxane and polysulfide impression materials. The presence of holes and/or relief did not significantly alter the magnitude of pressure. All impression materials produced pressure during maxillary edentulous impression making. Tray modification was not important in changing the amount of pressure produced. The impression materials used had more effect on the pressure produced during impression making on the simulated oral analog. Copyright 2002 by The American College of Prosthodontists.

  19. Design, modeling, expression, and chemoselective PEGylation of a new nanosize cysteine analog of erythropoietin.

    PubMed

    Cohan, Reza Ahangari; Madadkar-Sobhani, Armin; Khanahmad, Hossein; Roohvand, Farzin; Aghasadeghi, Mohammad Reza; Hedayati, Mohammad Hossein; Barghi, Zahra; Ardestani, Mehdi Shafiee; Inanlou, Davoud Nouri; Norouzian, Dariush

    2011-01-01

    Recombinant human erythropoietin (rhEPO) is considered to be one of the most pivotal pharmaceutical drugs in the market because of its clinical application in the treatment of anemia-associated disorders worldwide. However, like other therapeutic proteins, it does not have suitable pharmacokinetic properties for it to be administrated at least two to three times per week. Chemoselective cysteine PEGylation, employing molecular dynamics and graphics in in silico studies, can be considered to overcome such a problem. A special kind of EPO analog was elicited based on a literature review, homology modeling, molecular dynamic simulation, and factors affecting the PEGylation reaction. Then, cDNA of the selected analog was generated by site-directed mutagenesis and subsequently cloned into the expression vector. The construct was transfected to Chinese hamster ovary/dhfr(-) cells, and highly expressed clones were selected via methotrexate amplification. Ion-immobilized affinity and size exclusion (SE) chromatography techniques were used to purify the expressed analog. Thereafter, chemoselective PEGylation was performed and a nanosize PEGylated EPO was obtained through dialysis. The in vitro biologic assay and in vivo pharmacokinetic parameters were studied. Finally, E31C analog Fourier transform infrared, analytical SE-high-performance liquid chromatography, zeta potential, and size before and after PEGylation were characterized. The findings indicate that a novel nanosize EPO31-PEG has a five-fold longer terminal half-life in rats with similar biologic activity compared with unmodified rhEPO in proliferation cell assay. The results also show that EPO31-PEG size and charge versus unmodified protein was increased in a nanospectrum, and this may be one criterion of EPO biologic potency enhancement. This kind of novel engineered nanosize PEGylated EPO has remarkable advantages over rhEPO.

  20. Design, modeling, expression, and chemoselective PEGylation of a new nanosize cysteine analog of erythropoietin

    PubMed Central

    Cohan, Reza Ahangari; Madadkar-Sobhani, Armin; Khanahmad, Hossein; Roohvand, Farzin; Aghasadeghi, Mohammad Reza; Hedayati, Mohammad Hossein; Barghi, Zahra; Ardestani, Mehdi Shafiee; Inanlou, Davoud Nouri; Norouzian, Dariush

    2011-01-01

    Background: Recombinant human erythropoietin (rhEPO) is considered to be one of the most pivotal pharmaceutical drugs in the market because of its clinical application in the treatment of anemia-associated disorders worldwide. However, like other therapeutic proteins, it does not have suitable pharmacokinetic properties for it to be administrated at least two to three times per week. Chemoselective cysteine PEGylation, employing molecular dynamics and graphics in in silico studies, can be considered to overcome such a problem. Methods: A special kind of EPO analog was elicited based on a literature review, homology modeling, molecular dynamic simulation, and factors affecting the PEGylation reaction. Then, cDNA of the selected analog was generated by site-directed mutagenesis and subsequently cloned into the expression vector. The construct was transfected to Chinese hamster ovary/dhfr− cells, and highly expressed clones were selected via methotrexate amplification. Ion-immobilized affinity and size exclusion (SE) chromatography techniques were used to purify the expressed analog. Thereafter, chemoselective PEGylation was performed and a nanosize PEGylated EPO was obtained through dialysis. The in vitro biologic assay and in vivo pharmacokinetic parameters were studied. Finally, E31C analog Fourier transform infrared, analytical SE-high-performance liquid chromatography, zeta potential, and size before and after PEGylation were characterized. Results: The findings indicate that a novel nanosize EPO31-PEG has a five-fold longer terminal half-life in rats with similar biologic activity compared with unmodified rhEPO in proliferation cell assay. The results also show that EPO31-PEG size and charge versus unmodified protein was increased in a nanospectrum, and this may be one criterion of EPO biologic potency enhancement. Discussion: This kind of novel engineered nanosize PEGylated EPO has remarkable advantages over rhEPO. PMID:21753873

  1. Design and characterization of alpha-melanotropin peptide analogs cyclized through rhenium and technetium metal coordination.

    PubMed

    Giblin, M F; Wang, N; Hoffman, T J; Jurisson, S S; Quinn, T P

    1998-10-27

    alpha-Melanocyte stimulating hormone (alpha-MSH) analogs, cyclized through site-specific rhenium (Re) and technetium (Tc) metal coordination, were structurally characterized and analyzed for their abilities to bind alpha-MSH receptors present on melanoma cells and in tumor-bearing mice. Results from receptor-binding assays conducted with B16 F1 murine melanoma cells indicated that receptor-binding affinity was reduced to approximately 1% of its original levels after Re incorporation into the cyclic Cys4,10, D-Phe7-alpha-MSH4-13 analog. Structural analysis of the Re-peptide complex showed that the disulfide bond of the original peptide was replaced by thiolate-metal-thiolate cyclization. A comparison of the metal-bound and metal-free structures indicated that metal complexation dramatically altered the structure of the receptor-binding core sequence. Redesign of the metal binding site resulted in a second-generation Re-peptide complex (ReCCMSH) that displayed a receptor-binding affinity of 2.9 nM, 25-fold higher than the initial Re-alpha-MSH analog. Characterization of the second-generation Re-peptide complex indicated that the peptide was still cyclized through Re coordination, but the structure of the receptor-binding sequence was no longer constrained. The corresponding 99mTc- and 188ReCCMSH complexes were synthesized and shown to be stable in phosphate-buffered saline and to challenges from diethylenetriaminepentaacetic acid (DTPA) and free cysteine. In vivo, the 99mTcCCMSH complex exhibited significant tumor uptake and retention and was effective in imaging melanoma in a murine-tumor model system. Cyclization of alpha-MSH analogs via 99mTc and 188Re yields chemically stable and biologically active molecules with potential melanoma-imaging and therapeutic properties.

  2. Design of analog front-end circuitry with drift removal and gain enhancement for a highly sensitive handheld impedance cytometer

    NASA Astrophysics Data System (ADS)

    Talukder, Niloy

    We present a portable system for personalized blood cell counting consisting of a microfluidic impedance cytometer with portable analog readout feeding into an analog-to-digital converter (ADC). The novel design of the analog readout, which consists of a lock-in-amplifier followed by a high-pass filter stage for subtraction of drift and DC offset, and a post-subtraction high gain stage, enables detection of particles and cells as small as 1 mum in diameter, despite using a low-end 8 bit ADC. Applications such as personalized health monitoring require robust device operation and resilience to clogging, thus it is desirable to avoid using channels comparable in size to the particles being detected, thus requiring high levels of sensitivity. Despite using low-end off-the-shelf hardware, our sensing platform was capable of detecting changes in impedance as small as 0.032%, allowing detection of 3 mum diameter particles in 300 mum wide channel. The consecutive upward and downward signature of recorded peaks further helps to differentiate the signal from the noise floor. The performance of our system is comparable to that of a high-end bench-top impedance spectrometer under experimental condition. The novel analog design allowed for an instrument with a footprint of less than 80 cm2. The aim of this work was to demonstrate the potential of using microfluidic impedance spectroscopy for low-cost health monitoring. We demonstrated the utility of the platform technology towards cell counting, however our platform is broadly applicable to assaying wide panels of biomarkers including proteins, nucleic acids, and various cell types.

  3. Computational protein design to reengineer stromal cell-derived factor-1α generates an effective and translatable angiogenic polypeptide analog.

    PubMed

    Hiesinger, William; Perez-Aguilar, Jose Manuel; Atluri, Pavan; Marotta, Nicole A; Frederick, John R; Fitzpatrick, J Raymond; McCormick, Ryan C; Muenzer, Jeffrey R; Yang, Elaine C; Levit, Rebecca D; Yuan, Li-Jun; Macarthur, John W; Saven, Jeffery G; Woo, Y Joseph

    2011-09-13

    Experimentally, exogenous administration of recombinant stromal cell-derived factor-1α (SDF) enhances neovasculogenesis and cardiac function after myocardial infarction. Smaller analogs of SDF may provide translational advantages including enhanced stability and function, ease of synthesis, lower cost, and potential modulated delivery via engineered biomaterials. In this study, computational protein design was used to create a more efficient evolution of the native SDF protein. Protein structure modeling was used to engineer an SDF polypeptide analog (engineered SDF analog [ESA]) that splices the N-terminus (activation and binding) and C-terminus (extracellular stabilization) with a diproline segment designed to limit the conformational flexibility of the peptide backbone and retain the relative orientation of these segments observed in the native structure of SDF. Endothelial progenitor cells (EPCs) in ESA gradient, assayed by Boyden chamber, showed significantly increased migration compared with both SDF and control gradients. EPC receptor activation was evaluated by quantification of phosphorylated AKT, and cells treated with ESA yielded significantly greater phosphorylated AKT levels than SDF and control cells. Angiogenic growth factor assays revealed a distinct increase in angiopoietin-1 expression in the ESA- and SDF-treated hearts. In addition, CD-1 mice (n=30) underwent ligation of the left anterior descending coronary artery and peri-infarct intramyocardial injection of ESA, SDF-1α, or saline. At 2 weeks, echocardiography demonstrated a significant gain in ejection fraction, cardiac output, stroke volume, and fractional area change in mice treated with ESA compared with controls. Compared with native SDF, a novel engineered SDF polypeptide analog (ESA) more efficiently induces EPC migration and improves post-myocardial infarction cardiac function and thus offers a more clinically translatable neovasculogenic therapy.

  4. Design and evaluation of a low-level RF control system analog/digital receiver for the ILC main Linacs

    SciTech Connect

    Mavric, Uros; Vidmar, Matjaz; Chase, Brian; /Fermilab

    2008-06-01

    The proposed RF distribution scheme for the two 15 km long ILC LINACs, uses one klystron to feed 26 superconducting RF cavities operating at 1.3 GHz. For a precise control of the vector sum of the signals coming from the SC cavities, the control system needs a high performance, low cost, reliable and modular multichannel receiver. At Fermilab we developed a 96 channel, 1.3 GHz analog/digital receiver for the ILC LINAC LLRF control system. In the paper we present a balanced design approach to the specifications of each receiver section, the design choices made to fulfill the goals and a description of the prototyped system. The design is tested by measuring standard performance parameters, such as noise figure, linearity and temperature sensitivity. Measurements show that the design meets the specifications and it is comparable to other similar systems developed at other laboratories, in terms of performance.

  5. Spotlight on IC 3583

    NASA Image and Video Library

    2016-11-28

    This delicate blue group of stars — actually an irregular galaxy named IC 3583 — sits some 30 million light-years away in the constellation of Virgo (The Virgin). It may seem to have no discernable structure, but IC 3583 has been found to have a bar of stars running through its centre. These structures are common throughout the Universe, and are found within the majority of spiral, many irregular, and some lenticular galaxies. Two of our closest cosmic neighbours, the Large and Small Magellanic Clouds, are barred, indicating that they may have once been barred spiral galaxies that were disrupted or torn apart by the gravitational pull of the Milky Way. Something similar might be happening with IC 3583. This small galaxy is thought to be gravitationally interacting with one of its neighbours, the spiral Messier 90. Together, the duo form a pairing known as Arp 76. It’s still unclear whether these flirtations are the cause of IC 3583’s irregular appearance — but whatever the cause, the galaxy makes for a strikingly delicate sight in this NASA/ESA Hubble Space Telescope image, glimmering in the blackness of space.

  6. Design of transmission line driven slot waveguide Mach-Zehnder interferometers and application to analog optical links.

    PubMed

    Witzens, Jeremy; Baehr-Jones, Thomas; Hochberg, Michael

    2010-08-02

    Slot waveguides allow joint confinement of the driving electrical radio frequency field and of the optical waveguide mode in a narrow slot, allowing for highly efficient polymer based interferometers. We show that the optical confinement can be simply explained by a perturbation theoretical approach taking into account the continuity of the electric displacement field. We design phase matched transmission lines and show that their impedance and RF losses can be modeled by an equivalent circuit and linked to slot waveguide properties by a simple set of equations, thus allowing optimization of the device without iterative simulations. We optimize the interferometers for analog optical links and predict record performance metrics (V(pi) = 200 mV @ 10 GHz in push-pull configuration) assuming a modest second order nonlinear coefficient (r(33) = 50 pm/V) and slot width (100 nm). Using high performance optical polymers (r(33) = 150 pm/V), noise figures of state of the art analog optical links can be matched while reducing optical power levels by approximately 30 times. With required optical laser power levels predicted at 50 mW, this could be a game changing improvement by bringing high performance optical analog link power requirements in the reach of laser diodes. A modified transmitter architecture allows shot noise limited performance, while reducing power levels in the slot waveguides and enhancing reliability.

  7. Design and synthesis of gambogic acid analogs as potent cytotoxic and anti-inflammatory agents

    PubMed Central

    Yen, Chiao-Ting; Nakagawa-Goto, Kyoko; Hwang, Tsong-Long; Morris-Natschke, Susan L.; Bastow, Kenneth F.; Wu, Yang-Chang; Lee, Kuo-Hsiung

    2012-01-01

    Prenyl- and pyrano-xanthones derived from 1,3,6-trihydroxy-9H-xanthen-9-one, a basic backbone of gambogic acid (GA), were synthesized and evaluated for in vitro cytotoxic effects against four human cancer cell lines (KB, KBvin, A549, and DU-145) and anti-inflammatory activity toward superoxide anion generation and elastase release by human neutrophils in response to fMLP/CB. Among them, prenylxanthones 7-13 were generally less active than pyranoxanthones 14-21 in both anticancer and anti-inflammatory assays. Furthermore, two angular 3,3-dimethypyranoxanthones (16 and 20) showed the greatest and selective activity against the KBvin multidrug resistant (MDR) cell line with IC50 values of 0.9 and 0.8 μ g/mL, respectively. An angular 3-methyl-3-prenylpyranoxanthone (17) selectively inhibited elastase release with 200 times more potency than phenylmethylsulfonyl fluoride (PMSF), the positive control. PMID:22595179

  8. In silico design and analysis of a new hyperglycosylated analog of erythropoietin to improve drug efficacy

    PubMed Central

    Kianmehr, Anvarsadat; Mohammadi, Hamid Shahbaz; Shokrgozar, Mohammad Ali; Omidinia, Eskandar

    2015-01-01

    Background: The enhancement of glycosylation by applying glycoengineering approaches has become widely used to boost properties for protein therapeutics. The objective of this work was to engineer a new hyperglycosylated analog of erythropoietin (EPO) with appropriately targeted N-linked carbohydrates through bioinformatics tools. Materials and Methods: The EPO protein sequence was retrieved from NCBI protein sequence database. Prediction of N-glycosylation sites for the target protein was done using the prediction server, NetNGlyc. The three-dimensional model of glycoengineered EPO (named as kypoetin) was constructed using the homology modeling program. Ramchandran plot obtained from PROCHECK server was used to check stereochemical property. Meanwhile, 3D model of kypoetin with attached N-carbohydrates was built up using the GlyProt server. Results: In the new modified analog, three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 were inserted. Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 3D structural modeling showed that attached carbohydrates were on the proper spatial position. The whole solvent accessible surface areas of kypoetin (15132.69) were higher than EPO (9938.62). Conclusions: Totally, various model evaluation methods indicated that the glycoengineered version of EPO had considerably good geometry and acceptable profiles for clinical studies and could be considered as the effective drug. PMID:26322290

  9. In silico design and analysis of a new hyperglycosylated analog of erythropoietin to improve drug efficacy.

    PubMed

    Kianmehr, Anvarsadat; Mohammadi, Hamid Shahbaz; Shokrgozar, Mohammad Ali; Omidinia, Eskandar

    2015-01-01

    The enhancement of glycosylation by applying glycoengineering approaches has become widely used to boost properties for protein therapeutics. The objective of this work was to engineer a new hyperglycosylated analog of erythropoietin (EPO) with appropriately targeted N-linked carbohydrates through bioinformatics tools. The EPO protein sequence was retrieved from NCBI protein sequence database. Prediction of N-glycosylation sites for the target protein was done using the prediction server, NetNGlyc. The three-dimensional model of glycoengineered EPO (named as kypoetin) was constructed using the homology modeling program. Ramchandran plot obtained from PROCHECK server was used to check stereochemical property. Meanwhile, 3D model of kypoetin with attached N-carbohydrates was built up using the GlyProt server. In the new modified analog, three additional N-glycosylation sites at amino-acid positions 30, 34 and 86 were inserted. Ramchandran plot analysis showed 81.6% of the residues in the most favored region, 15.6% in the additional allowed, 1.4% in the generously allowed regions and 1.4% in the disallowed region. 3D structural modeling showed that attached carbohydrates were on the proper spatial position. The whole solvent accessible surface areas of kypoetin (15132.69) were higher than EPO (9938.62). Totally, various model evaluation methods indicated that the glycoengineered version of EPO had considerably good geometry and acceptable profiles for clinical studies and could be considered as the effective drug.

  10. Design and Operation of a 9-bit Single-flux-quantum Pulse-frequency Modulation Digital-to-analog Converter

    NASA Astrophysics Data System (ADS)

    Mizugaki, Yoshinao; Takahashi, Yoshitaka; Shimada, Hiroshi; Maezawa, Masaaki

    We designed and operated a 9-bit single-flux-quantum (SFQ) digital-to-analog converter (DAC). SFQ pulse-frequency modulation (PFM) was employed for generation of variable quantum output voltage, where a 9-bit variable pulse number multiplier and a 100-fold voltage multiplier were the key components. Test chips were fabricated using a Nb Josephson integration technology. Arbitrary voltage waveforms were synthesized with the maximum voltage of 2.54 mV. For ac voltage standard applications, relationships between the DAC resolution and the synthesized waveform frequency are discussed.

  11. Computer-guided design, synthesis, and protein kinase C affinity of a new salicylate-based class of bryostatin analogs.

    PubMed

    Wender, Paul A; Nakagawa, Yu; Near, Katherine E; Staveness, Daryl

    2014-10-03

    Bryostatin 1 is in clinical trials for the treatment of cancer and Alzheimer's disease and is a candidate for a first-in-class approach to HIV/AIDS eradication. It is neither readily available nor optimally suited for clinical use. Using a function oriented synthesis strategy, a new class of bryostatin-inspired analogs was designed with a simplified salicylate-derived subunit, enabling step-economical synthesis (23 total steps) of agents exhibiting bryostatin-like affinity to protein kinase C (PKC).

  12. Automatic Synthesis of CMOS Algorithmic Analog To-Digital Converter.

    NASA Astrophysics Data System (ADS)

    Jusuf, Gani

    The steady decrease in technological feature size is allowing increasing levels of integration in analog/digital interface functions. These functions consist of analog as well as digital circuits. While the turn around time for an all digital IC chip is very short due to the maturity of digital IC computer-aided design (CAD) tools over the last ten years, most analog circuits have to be designed manually due to the lack of analog IC CAD tools. As a result, analog circuit design becomes the bottleneck in the design of mixed signal processing chips. One common analog function in a mixed signal processing chip is an analog-to-digital conversion (ADC) function. This function recurs frequently but with varying performance requirements. The objective of this research is to study the design methodology of a compilation program capable of synthesizing ADC's with a broad range of sampling rates and resolution, and silicon area and performance comparable with the manual approach. The automatic compilation of the ADC function is a difficult problem mainly because ADC techniques span such a wide spectrum of performance, with radically different implementations being optimum for different ranges of conversion range, resolution, and power dissipation. We will show that a proper choice of the ADC architectures and the incorporation of many analog circuit design techniques will simplify the synthesis procedure tremendously. Moreover, in order to speed up the device sizing, hierarchical optimization procedure and behavioral simulation are implemented into the ADC module generation steps. As a result of this study, a new improved algorithmic ADC without the need of high precision comparators has been developed. This type of ADC lends itself to automatic generation due to its modularity, simplicity, small area consumption, moderate speed, low power dissipation, and single parameter trim capability that can be added at high resolution. Furthermore, a performance-driven CMOS ADC module

  13. The logic and design of analog-sensitive kinases and their small molecule inhibitors.

    PubMed

    Lopez, Michael S; Kliegman, Joseph I; Shokat, Kevan M

    2014-01-01

    Analog-sensitive AS Kinase technology allows for rapid, reversible, and highly specific inhibition of individual engineered kinases in cells and in mouse models of human diseases. The technique consists of two parts: a kinase containing a space-creating mutation in the ATP-binding pocket and a bulky ATP-competitive small molecule inhibitor that complements the shape of the mutant ATP pocket. This strategy enables dissection of phospho-signaling pathways, elucidation of the physiological function of individual kinases, and characterization of the pharmacology of clinical-kinase inhibitors. Here, we present an overview of AS technology and describe a stepwise approach for generating AS Kinase mutants and identifying appropriate small molecule inhibitors. We also describe commonly encountered technical obstacles and provide strategies to overcome them.

  14. Structural studies provide clues for analog design of specific inhibitors of Cryptosporidium hominis thymidylate synthase-dihydrofolate reductase.

    PubMed

    Kumar, Vidya P; Cisneros, Jose A; Frey, Kathleen M; Castellanos-Gonzalez, Alejandro; Wang, Yiqiang; Gangjee, Aleem; White, A Clinton; Jorgensen, William L; Anderson, Karen S

    2014-09-01

    Cryptosporidium is the causative agent of a gastrointestinal disease, cryptosporidiosis, which is often fatal in immunocompromised individuals and children. Thymidylate synthase (TS) and dihydrofolate reductase (DHFR) are essential enzymes in the folate biosynthesis pathway and are well established as drug targets in cancer, bacterial infections, and malaria. Cryptosporidium hominis has a bifunctional thymidylate synthase and dihydrofolate reductase enzyme, compared to separate enzymes in the host. We evaluated lead compound 1 from a novel series of antifolates, 2-amino-4-oxo-5-substituted pyrrolo[2,3-d]pyrimidines as an inhibitor of Cryptosporidium hominis thymidylate synthase with selectivity over the human enzyme. Complementing the enzyme inhibition compound 1 also has anti-cryptosporidial activity in cell culture. A crystal structure with compound 1 bound to the TS active site is discussed in terms of several van der Waals, hydrophobic and hydrogen bond interactions with the protein residues and the substrate analog 5-fluorodeoxyuridine monophosphate (TS), cofactor NADPH and inhibitor methotrexate (DHFR). Another crystal structure in complex with compound 1 bound in both the TS and DHFR active sites is also reported here. The crystal structures provide clues for analog design and for the design of ChTS-DHFR specific inhibitors. Copyright © 2014. Published by Elsevier Ltd.

  15. Application of Adaptive Design Methodology in Development of a Long-Acting Glucagon-Like Peptide-1 Analog (Dulaglutide): Statistical Design and Simulations

    PubMed Central

    Skrivanek, Zachary; Berry, Scott; Berry, Don; Chien, Jenny; Geiger, Mary Jane; Anderson, James H.; Gaydos, Brenda

    2012-01-01

    Background Dulaglutide (dula, LY2189265), a long-acting glucagon-like peptide-1 analog, is being developed to treat type 2 diabetes mellitus. Methods To foster the development of dula, we designed a two-stage adaptive, dose-finding, inferentially seamless phase 2/3 study. The Bayesian theoretical framework is used to adaptively randomize patients in stage 1 to 7 dula doses and, at the decision point, to either stop for futility or to select up to 2 dula doses for stage 2. After dose selection, patients continue to be randomized to the selected dula doses or comparator arms. Data from patients assigned the selected doses will be pooled across both stages and analyzed with an analysis of covariance model, using baseline hemoglobin A1c and country as covariates. The operating characteristics of the trial were assessed by extensive simulation studies. Results Simulations demonstrated that the adaptive design would identify the correct doses 88% of the time, compared to as low as 6% for a fixed-dose design (the latter value based on frequentist decision rules analogous to the Bayesian decision rules for adaptive design). Conclusions This article discusses the decision rules used to select the dula dose(s); the mathematical details of the adaptive algorithm—including a description of the clinical utility index used to mathematically quantify the desirability of a dose based on safety and efficacy measurements; and a description of the simulation process and results that quantify the operating characteristics of the design. PMID:23294775

  16. Application of adaptive design methodology in development of a long-acting glucagon-like peptide-1 analog (dulaglutide): statistical design and simulations.

    PubMed

    Skrivanek, Zachary; Berry, Scott; Berry, Don; Chien, Jenny; Geiger, Mary Jane; Anderson, James H; Gaydos, Brenda

    2012-11-01

    Dulaglutide (dula, LY2189265), a long-acting glucagon-like peptide-1 analog, is being developed to treat type 2 diabetes mellitus. To foster the development of dula, we designed a two-stage adaptive, dose-finding, inferentially seamless phase 2/3 study. The Bayesian theoretical framework is used to adaptively randomize patients in stage 1 to 7 dula doses and, at the decision point, to either stop for futility or to select up to 2 dula doses for stage 2. After dose selection, patients continue to be randomized to the selected dula doses or comparator arms. Data from patients assigned the selected doses will be pooled across both stages and analyzed with an analysis of covariance model, using baseline hemoglobin A1c and country as covariates. The operating characteristics of the trial were assessed by extensive simulation studies. Simulations demonstrated that the adaptive design would identify the correct doses 88% of the time, compared to as low as 6% for a fixed-dose design (the latter value based on frequentist decision rules analogous to the Bayesian decision rules for adaptive design). This article discusses the decision rules used to select the dula dose(s); the mathematical details of the adaptive algorithm-including a description of the clinical utility index used to mathematically quantify the desirability of a dose based on safety and efficacy measurements; and a description of the simulation process and results that quantify the operating characteristics of the design. © 2012 Diabetes Technology Society.

  17. Design, synthesis and in vitro biological evaluation of short-chain C12-sphinganine and its 1,2,3-triazole analogs as potential antimicrobial and anti-biofilm agents.

    PubMed

    Vijai Kumar Reddy, T; Jyotsna, A; Prabhavathi Devi, B L A; Prasad, R B N; Poornachandra, Y; Ganesh Kumar, C

    2016-08-08

    A conceptual synthetic approach of short-chain C12-sphinganine 1 and a small library of its 1,2,3-triazole analogs 2(a-f) has been accomplished using the commercially available and inexpensive 10-undecenoic acid as a starting material. Miyashita's C-2 selective endo mode azidolysis and Huisgen click reaction was employed for the synthesis of the designed analogs. Based on biological evaluation studies of all the synthesized compounds, it was observed that, (2S,3R)-2-(4-(3-hydroxyphenyl)-1H-1,2,3-triazol-1-yl)dodecan-1,3-diol (2b) exhibited promising antimicrobial and antifungal activities. Furthermore, compound 2b was able to inhibit the biofilm formation of Candida albicans MTCC 227, Micrococcus luteus MTCC 2470 and Staphylococcus aureus MTCC 96 with IC50 values of 1.9, 2.1 and 2.9 μg/mL, respectively. Compound 2b increased the levels of reactive oxygen species (ROS) in C. albicans MTCC 227. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. D-optimal design applied to binding saturation curves of an enkephalin analog in rat brain

    SciTech Connect

    Verotta, D.; Petrillo, P.; La Regina, A.; Rocchetti, M.; Tavani, A.

    1988-01-01

    The D-optimal design, a minimal sample design that minimizes the volume of the joint confidence region for the parameters, was used to evaluate binding parameters in a saturation curve with a view to reducing the number of experimental points without loosing accuracy in binding parameter estimates. Binding saturation experiments were performed in rat brain crude membrane preparations with the opioid ..mu..-selective ligand (/sup 3/H)-(D-Ala/sup 2/, MePhe/sup 4/, Gly-ol/sup 5/)enkephalin (DAGO), using a sequential procedure. The first experiment consisted of a wide-range saturation curve, which confirmed that (/sup 3/H)-DAGO binds only one class of specific sites and non-specific sites, and gave information on the experimental range and a first estimate of binding affinity (K/sub a/), capacity (B/sub max/) and non-specific constant (k). On this basis the D-optimal design was computed and sequential experiments were performed each covering a wide-range traditional saturation curve, the D-optimal design and a splitting of the D-optimal design with the addition of 2 points (+/- 15% of the central point). No appreciable differences were obtained with these designs in parameter estimates and their accuracy. Thus, sequential experiments based on D-optimal design seem a valid method for accurate determination of binding parameters, using far fewer points with no loss in parameter estimation accuracy. 25 references, 2 figures, 3 tables.

  19. A Design of a New Column-Parallel Analog-to-Digital Converter Flash for Monolithic Active Pixel Sensor.

    PubMed

    Chakir, Mostafa; Akhamal, Hicham; Qjidaa, Hassan

    2017-01-01

    The CMOS Monolithic Active Pixel Sensor (MAPS) for the International Linear Collider (ILC) vertex detector (VXD) expresses stringent requirements on their analog readout electronics, specifically on the analog-to-digital converter (ADC). This paper concerns designing and optimizing a new architecture of a low power, high speed, and small-area 4-bit column-parallel ADC Flash. Later in this study, we propose to interpose an S/H block in the converter. This integration of S/H block increases the sensitiveness of the converter to the very small amplitude of the input signal from the sensor and provides a sufficient time to the converter to be able to code the input signal. This ADC is developed in 0.18 μm CMOS process with a pixel pitch of 35 μm. The proposed ADC responds to the constraints of power dissipation, size, and speed for the MAPS composed of a matrix of 64 rows and 48 columns where each column ADC covers a small area of 35 × 336.76 μm(2). The proposed ADC consumes low power at a 1.8 V supply and 100 MS/s sampling rate with dynamic range of 125 mV. Its DNL and INL are 0.0812/-0.0787 LSB and 0.0811/-0.0787 LSB, respectively. Furthermore, this ADC achieves a high speed more than 5 GHz.

  20. Computer-assisted combinatorial design of bicyclic thymidine analogs as inhibitors of Mycobacterium tuberculosis thymidine monophosphate kinase

    NASA Astrophysics Data System (ADS)

    Frecer, Vladimir; Seneci, Pierfausto; Miertus, Stanislav

    2011-01-01

    Thymidine monophosphate kinase (TMPKmt) is an essential enzyme for nucleotide metabolism in Mycobacterium tuberculosis, and thus an attractive target for novel antituberculosis agents. In this work, we have explored the chemical space around the 2',3'-bicyclic thymidine nucleus by designing and in silico screening of a virtual focused library selected via structure based methods to identify more potent analogs endowed with favorable ADME-related properties. In all the library members we have exchanged the ribose ring of the template with a cyclopentane moiety that is less prone to enzymatic degradation. In addition, we have replaced the six-membered 2',3'-ring by a number of five-membered and six-membered heterocyclic rings containing alternative proton donor and acceptor groups, to exploit the interaction with the carboxylate groups of Asp9 and Asp163 as well as with several cationic residues present in the vicinity of the TMPKmt binding site. The three-dimensional structure of the TMPKmt complexed with 5-hydroxymethyl-dUMP, an analog of dTMP, was employed to develop a QSAR model, to parameterize a scoring function specific for the TMPKmt target and to select analogues which display the highest predicted binding to the target. As a result, we identified a small highly focused combinatorial subset of bicyclic thymidine analogues as virtual hits that are predicted to inhibit the mycobacterial TMPK in the submicromolar concentration range and to display favorable ADME-related properties.

  1. Comparing Binding Modes of Analogous Fragments Using NMR in Fragment-Based Drug Design: Application to PRDX5

    PubMed Central

    Guichou, Jean-François; Cala, Olivier; Krimm, Isabelle

    2014-01-01

    Fragment-based drug design is one of the most promising approaches for discovering novel and potent inhibitors against therapeutic targets. The first step of the process consists of identifying fragments that bind the protein target. The determination of the fragment binding mode plays a major role in the selection of the fragment hits that will be processed into drug-like compounds. Comparing the binding modes of analogous fragments is a critical task, not only to identify specific interactions between the protein target and the fragment, but also to verify whether the binding mode is conserved or differs according to the fragment modification. While X-ray crystallography is the technique of choice, NMR methods are helpful when this fails. We show here how the ligand-observed saturation transfer difference (STD) experiment and the protein-observed 15N-HSQC experiment, two popular NMR screening experiments, can be used to compare the binding modes of analogous fragments. We discuss the application and limitations of these approaches based on STD-epitope mapping, chemical shift perturbation (CSP) calculation and comparative CSP sign analysis, using the human peroxiredoxin 5 as a protein model. PMID:25025339

  2. Design and optimization of polymer ring resonator modulators for analog microwave photonic applications

    NASA Astrophysics Data System (ADS)

    Hosseinzadeh, Arash; Middlebrook, Christopher T.

    2016-02-01

    Efficient modulation of electrical signals onto an optical carrier remains the main challenge in full implementation of microwave photonic links (MPLs) for applications such as antenna remoting and wireless access networks. Current MPLs utilize Mach-Zehnder Interferometers (MZI) with sinusoidal transfer function as electro-optic modulators causing nonlinear distortions in the link. Recently ring resonator modulators (RRM) consisting of a ring resonator coupled to a base waveguide attracted interest to enhance linearity, reduce the size and power consumption in MPLs. Fabrication of a RRM is more challenging than the MZI not only in fabrication process but also in designing and optimization steps. Although RRM can be analyzed theoretically for MPLs, physical structures need to be designed and optimized utilizing simulation techniques in both optical and microwave regimes with consideration of specific material properties. Designing and optimization steps are conducted utilizing full-wave simulation software package and RRM function analyzed in both passive and active forms and confirmed through theoretical analysis. It is shown that RRM can be completely designed and analyzed utilizing full-wave simulation techniques and as a result linearity effect of the modulator on MPLs can be studied and optimized. The material nonlinearity response can be determined computationally and included in modulator design and readily adaptable for analyzing other materials such as silicon or structures where theoretical analysis is not easily achieved.

  3. Design, analysis and optimization of switched-capacitor filters derived from lumped analog models

    NASA Astrophysics Data System (ADS)

    Haug, K.

    1981-08-01

    The considered investigation makes use of the signal flow graph (SFG) procedure developed by Brodersen et al. (1979). This approach is employed in connection with the low sensitivity of the transfer function against parameter variations and the small effect of stray capacitances inherent in the SFG procedure. The design of switched-capacitor (SC) filters is illustrated with the aid of an example, involving a fifth degree PCM low-pass filter. The purpose of the design procedure is to obtain a filter structure whose frequency determining elements are integrators. Attention is given to the reduction of the distortion caused by the additional delay, the application of a design centering procedure for eliminating distortion, the optimization of the dynamic range, and parasitic effects.

  4. Design of a reliable PUF circuit based on R-2R ladder digital-to-analog convertor

    NASA Astrophysics Data System (ADS)

    Pengjun, Wang; Xuelong, Zhang; Yuejun, Zhang; Jianrui, Li

    2015-07-01

    A novel physical unclonable functions (PUF) circuit is proposed, which relies on non-linear characteristic of analog voltage generated by R-2R ladder DAC. After amplifying the deviation signal, the robustness of the DAC-PUF circuit has increased significantly. The DAC-PUF circuit is designed in TSMC 65 nm CMOS technology and the layout occupies 86.06 × 63.56 μm2. Monte Carlo simulation results show that the reliability of the DAC-PUF circuit is above 98% over a comprehensive range of environmental variation, such as temperature and supply voltage. Project supported by the National Natural Science Foundation of China (Nos. 61474068, 61404076, 61274132), the Zhejiang Provincial Natural Science Foundation of China (No. LQ14F040001), and the K. C. Wong Magna Fund in Ningbo University, China.

  5. The design and fabrication of three-chamber microscale cell culture analog devices with integrated dissolved oxygen sensors.

    PubMed

    Sin, Aaron; Chin, Katherine C; Jamil, Muhammad F; Kostov, Yordan; Rao, Govind; Shuler, Michael L

    2004-01-01

    Whole animal testing is an essential part in evaluating the toxicological and pharmacological profiles of chemicals and pharmaceuticals, but these experiments are expensive and cumbersome. A cell culture analog (CCA) system, when used in conjunction with a physiologically based pharmacokinetic (PBPK) model, provides an in vitro supplement to animal studies and the possibility of a human surrogate for predicting human response in clinical trials. A PBPK model mathematically simulates animal metabolism by modeling the absorption, distribution, metabolism, and elimination kinetics of a chemical in interconnected tissue compartments. A CCA uses mammalian cells cultured in interconnected chambers to physically represent the corresponding PBPK. These compartments are connected by recirculating tissue culture medium that acts as a blood surrogate. The purpose of this article is to describe the design and basic operation of the microscale manifestation of such a system. Microscale CCAs offer the potential for inexpensive, relatively high throughput evaluation of chemicals while minimizing demand for reagents and cells. Using microfabrication technology, a three-chamber ("lung"-"liver"-"other") microscale cell culture analog (microCCA) device was fabricated on a 1 in. (2.54 cm) square silicon chip. With a design flow rate of 1.76 microL/min, this microCCA device achieves approximate physiological liquid-to-cell ratio and hydrodynamic shear stress while replicating the liquid residence time parameters in the PBPK model. A dissolved oxygen sensor based on collision quenching of a fluorescent ruthenium complex by oxygen molecules was integrated into the system, demonstrating the potential to integrate real-time sensors into such devices.

  6. Building Digital Libraries for Analog People: Ten Common Design Pitfalls and How To Avoid Them.

    ERIC Educational Resources Information Center

    Johnson, Doug

    2000-01-01

    Reviews design factors to consider when planning library media centers. Highlights include planning teams; planning for more than one kind of learning; considering community as well as school use; planning for existing technology rather than future possibilities; considering ease of supervision; traffic patterns; lighting and sound damping; and…

  7. Building Digital Libraries for Analog People: Ten Common Design Pitfalls and How To Avoid Them.

    ERIC Educational Resources Information Center

    Johnson, Doug

    2000-01-01

    Reviews design factors to consider when planning library media centers. Highlights include planning teams; planning for more than one kind of learning; considering community as well as school use; planning for existing technology rather than future possibilities; considering ease of supervision; traffic patterns; lighting and sound damping; and…

  8. In Silico Analog Design for Terbinafine Against Trichophyton rubrum: A Preliminary Study.

    PubMed

    Karumuri, Sudha; Singh, Puneet Kumar; Shukla, Pratyoosh

    2015-09-01

    The diseases caused by dermatophytes are common among several other infections which cause serious threat to human health. It is evident that enzyme squalene epoxidase is responsible for prolonged dermatophyte infection and it is appealing to note that this enzyme is also responsible for fatty acid synthesis in these groups of fungi. In the present study, terbinafine drug which targets enzyme squalene epoxidase has been explored to design its various novel analogues. The present study suggests that many more prominent drug analogues could be constituted which may be crucial towards designing new drug candidates. In the present study, we have designed a series of such analogues viz. [(2E)-6,6-dimethylhept-2-en-4-yn-1-yl](methyl)(naphthalen-1-ylmethyl)amine, N-[8-({[(2E)-6,6-dimethylhept-2-en-4-yn-1-yl](methyl)amino}methyl)naphthalen-1-yl]-2-(sulfoamino) acetamide, {[4-(dihydroxyamino)-8-({[(2E)-6,6-dimethylhept-2-en-4-yn-1-yl](methyl)amino}methyl)naphthalen-1-yl]sulfanyl}methanol and (R)-{[4-({[(2E,6R)-6,7-dimethyloct-2-en-4-yn-1-yl](methyl)amino}methyl)-5-[(hydroxysulfamoyl)amino]naphthalen-1-yl]amino}sulfinic acid. Moreover, further by molecular docking approach the binding between enzyme and designed analogues was further analysed. The present preliminary report suggested a considerably good docking interaction score of -338.75 kcal/mol between terbinafine and squalene epoxidase from Trichophyton rubrum. This preliminary study implies that few designed candidate ligands can be effectual towards the activity of this enzyme and can play crucial role in pathogenesis control of T. rubrum.

  9. EXTRACTION AND DETECTION OF A NEW ARSINE SULFIDE CONTAINING ARSENOSUGAR IN MOLLUSCS BY IC-ICP-MS AND IC-ESI-MS/MS

    EPA Science Inventory

    Using IC-ICP-MS and IC-ESI-MS/MS, an unknown arsenical compound in mollusks has been identified as a new arsine sulfide containing analog of a known arsenosugar and is referred to as As(498). This species has been observed in four separate shellfish species following a mild metha...

  10. Design and synthesis of benzodiazepine analogs as isoform-selective human lysine deacetylase inhibitors.

    PubMed

    Reddy, D Rajasekhar; Ballante, Flavio; Zhou, Nancy J; Marshall, Garland R

    2017-02-15

    A comprehensive investigation was performed to identify new benzodiazepine (BZD) derivatives as potent and selective human lysine deacetylase inhibitors (hKDACis). A total of 108 BZD compounds were designed, synthesized and from that 104 compounds were biologically evaluated against human lysine deacetylases (hKDACs) 1, 3 and 8 (class I) and 6 (class IIb). The most active compounds showed mid-nanomolar potencies against hKDACs 1, 3 and 6 and micromolar activity against hKDAC8, while a promising compound (6q) showed selectivity towards hKDAC3 among the different enzyme isoforms. An hKDAC6 homology model, refined by molecular dynamics simulation was generated, and molecular docking studies performed to rationalize the dominant ligand-residue interactions as well as to define structure-activity-relationships. Experimental results confirmed the usefulness of the benzodiazepine moiety as capping group when pursuing hKDAC isoform-selectivity inhibition, suggesting its continued use when designing new hKDACis.

  11. Functional Recovery of Analog Circuits at Extreme Temperatures

    NASA Technical Reports Server (NTRS)

    Zebulum, Ricardo S.; Stoica, Adrian; Keymeulen, Didier; Ramesham, Rajeshuni; Neff, Joseph; Katkoori, Srinivas

    2006-01-01

    This paper describes a new reconfigurable analog array (RAA) architecture and integrated circuit (IC) used to map analog circuits that can adapt to extreme temperatures under programmable control. Algorithm-driven adaptation takes place on the RAA IC. The algorithms are implemented in a separate Field Programmable Gate Array (FPGA) IC, co-located with the RAA in the extreme temperature environment. The experiments demonstrate circuit adaptation over a wide temperature range, from extremely low temperature of -180 C to high 120 C.

  12. Temperature-adaptive Circuits on Reconfigurable Analog Arrays

    NASA Technical Reports Server (NTRS)

    Stoica, Adrian; Zebulum, Ricardo S.; Keymeulen, Didier; Ramesham, Rajeshuni; Neff, Joseph; Katkoori, Srinivas

    2006-01-01

    This paper describes a new reconfigurable analog array (MA) architecture and integrated circuit (IC) used to map analog circuits that can adapt to extreme temperatures under programmable control. Algorithm-driven adaptation takes place on the RAA IC. The algorithms are implemented in a separate Field Programmable Gate Array (FPGA) IC, co-located with the RAA in the extreme temperature environment. The experiments demonstrate circuit adaptation over a wide temperature range, from extremely low temperature of -180 C to high 120 C.

  13. Temperature-adaptive Circuits on Reconfigurable Analog Arrays

    NASA Technical Reports Server (NTRS)

    Stoica, Adrian; Zebulum, Ricardo S.; Keymeulen, Didier; Ramesham, Rajeshuni; Neff, Joseph; Katkoori, Srinivas

    2006-01-01

    This paper describes a new reconfigurable analog array (MA) architecture and integrated circuit (IC) used to map analog circuits that can adapt to extreme temperatures under programmable control. Algorithm-driven adaptation takes place on the RAA IC. The algorithms are implemented in a separate Field Programmable Gate Array (FPGA) IC, co-located with the RAA in the extreme temperature environment. The experiments demonstrate circuit adaptation over a wide temperature range, from extremely low temperature of -180 C to high 120 C.

  14. Functional Recovery of Analog Circuits at Extreme Temperatures

    NASA Technical Reports Server (NTRS)

    Zebulum, Ricardo S.; Stoica, Adrian; Keymeulen, Didier; Ramesham, Rajeshuni; Neff, Joseph; Katkoori, Srinivas

    2006-01-01

    This paper describes a new reconfigurable analog array (RAA) architecture and integrated circuit (IC) used to map analog circuits that can adapt to extreme temperatures under programmable control. Algorithm-driven adaptation takes place on the RAA IC. The algorithms are implemented in a separate Field Programmable Gate Array (FPGA) IC, co-located with the RAA in the extreme temperature environment. The experiments demonstrate circuit adaptation over a wide temperature range, from extremely low temperature of -180 C to high 120 C.

  15. A Design of a New Column-Parallel Analog-to-Digital Converter Flash for Monolithic Active Pixel Sensor

    PubMed Central

    Qjidaa, Hassan

    2017-01-01

    The CMOS Monolithic Active Pixel Sensor (MAPS) for the International Linear Collider (ILC) vertex detector (VXD) expresses stringent requirements on their analog readout electronics, specifically on the analog-to-digital converter (ADC). This paper concerns designing and optimizing a new architecture of a low power, high speed, and small-area 4-bit column-parallel ADC Flash. Later in this study, we propose to interpose an S/H block in the converter. This integration of S/H block increases the sensitiveness of the converter to the very small amplitude of the input signal from the sensor and provides a sufficient time to the converter to be able to code the input signal. This ADC is developed in 0.18 μm CMOS process with a pixel pitch of 35 μm. The proposed ADC responds to the constraints of power dissipation, size, and speed for the MAPS composed of a matrix of 64 rows and 48 columns where each column ADC covers a small area of 35 × 336.76 μm2. The proposed ADC consumes low power at a 1.8 V supply and 100 MS/s sampling rate with dynamic range of 125 mV. Its DNL and INL are 0.0812/−0.0787 LSB and 0.0811/−0.0787 LSB, respectively. Furthermore, this ADC achieves a high speed more than 5 GHz. PMID:28243628

  16. Rational design of an AKR1C3-resistant analog of PR-104 for enzyme-prodrug therapy.

    PubMed

    Mowday, Alexandra M; Ashoorzadeh, Amir; Williams, Elsie M; Copp, Janine N; Silva, Shevan; Bull, Matthew R; Abbattista, Maria R; Anderson, Robert F; Flanagan, Jack U; Guise, Christopher P; Ackerley, David F; Smaill, Jeff B; Patterson, Adam V

    2016-09-15

    The clinical stage anti-cancer agent PR-104 has potential utility as a cytotoxic prodrug for exogenous bacterial nitroreductases expressed from replicating vector platforms. However substrate selectivity is compromised due to metabolism by the human one- and two-electron oxidoreductases cytochrome P450 oxidoreductase (POR) and aldo-keto reductase 1C3 (AKR1C3). Using rational drug design we developed a novel mono-nitro analog of PR-104A that is essentially free of this off-target activity in vitro and in vivo. Unlike PR-104A, there was no biologically relevant cytotoxicity in cells engineered to express AKR1C3 or POR, under aerobic or anoxic conditions, respectively. We screened this inert prodrug analog, SN34507, against a type I bacterial nitroreductase library and identified E. coli NfsA as an efficient bioactivator using a DNA damage response assay and recombinant enzyme kinetics. Expression of E. coli NfsA in human colorectal cancer cells led to selective cytotoxicity to SN34507 that was associated with cell cycle arrest and generated a robust 'bystander effect' at tissue-like cell densities when only 3% of cells were NfsA positive. Anti-tumor activity of SN35539, the phosphate pre-prodrug of SN34507, was established in 'mixed' tumors harboring a minority of NfsA-positive cells and demonstrated marked tumor control following heterogeneous suicide gene expression. These experiments demonstrate that off-target metabolism of PR-104 can be avoided and identify the suicide gene/prodrug partnership of E. coli NfsA/SN35539 as a promising combination for development in armed vectors. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. A Multiwavelength Study of IC 63 and IC 59

    NASA Astrophysics Data System (ADS)

    Karr, J. L.; Noriega-Crespo, A.; Martin, P. G.

    2005-02-01

    IC 63 and IC 59 are two nearby arc-shaped nebulae with relatively simple geometries and minimal obscuring material. The two regions, in spite of a similar projected distance from their ionizing star, have very different observational properties, both in continuum emission and in the presence and strength of line emission from molecular species. This paper conducts a multiwavelength study of the two regions using archived data from a variety of sources, including the Canadian Galactic Plane Survey and the Infrared Space Observatory. The multiwavelength morphology and structure of the two nebulae are studied in detail, particularly the ionization fronts in IC 63. The possibility of triggered star formation in IC 63 is investigated and determined to be spurious. H2 and polycyclic aromatic hydrocarbon emission is detected in both IC 63 and IC 59, confirming the presence of molecular hydrogen in IC 59. The averaged line ratios are similar in the two regions, but variations are seen within each region. Temperatures and densities were calculated from the S(3) and S(5) pure rotational lines of molecular hydrogen. We derived a temperature of 630 K in IC 63, comparable to previous results, and a column density of 5.8×1017 cm-2, somewhat lower than previous values. New results for IC 59 show values of 590 K and 3.4×1017 cm-2, slightly cooler and with lower column density than IC 63. The contrast in appearance between IC 63 and IC 59 is consistent with a difference in actual (rather than projected) distances and a small variation in temperature and column density.

  18. Embedded I&C for Extreme Environments

    SciTech Connect

    Kisner, Roger A.

    2016-04-01

    This project uses embedded instrumentation and control (I&C) technologies to demonstrate potential performance gains of nuclear power plant components in extreme environments. Extreme environments include high temperature, radiation, high pressure, high vibration, and high EMI conditions. For extreme environments, performance gains arise from moment-to-moment sensing of local variables and immediate application of local feedback control. Planning for embedding I&C during early system design phases contrasts with the traditional, serial design approach that incorporates minimal I&C after mechanical and electrical design is complete. The demonstration application involves the development and control of a novel, proof-of-concept motor/pump design. The motor and pump combination operate within the fluid environment, eliminating the need for rotating seals. Actively controlled magnetic bearings also replace failure-prone mechanical contact bearings that typically suspend rotating components. Such as design has the potential to significantly enhance the reliability and life of the pumping system and would not be possible without embedded I&C.

  19. Structure-based design, synthesis and biological testing of etoposide analog epipodophyllotoxin-N-mustard hybrid compounds designed to covalently bind to topoisomerase II and DNA

    PubMed Central

    Yadav, Arun A.; Wu, Xing; Patel, Daywin; Yalowich, Jack C.; Hasinoff, Brian B.

    2014-01-01

    Drugs that target DNA topoisomerase II isoforms and alkylate DNA represent two mechanistically distinct and clinically important classes of anticancer drugs. Guided by molecular modeling and docking a series of etoposide analog epipodophyllotoxin-N-mustard hybrid compounds were designed, synthesized and biologically characterized. These hybrids were designed to alkylate nucleophilic protein residues on topoisomerase II and thus produce inactive covalent adducts and to also alkylate DNA. The most potent hybrid had a mean GI50 in the NCI-60 cell screen 17-fold lower than etoposide. Using a variety of in vitro and cell-based assays all of the hybrids tested were shown to target topoisomerase II. A COMPARE analysis indicated that the hybrids had NCI 60-cell growth inhibition profiles matching both etoposide and the N-mustard compounds from which they were derived. These results supported the conclusion that the hybrids displayed characteristics that were consistent with having targeted both topoisomerase II and DNA. PMID:25282653

  20. Design, synthesis and crystallization of a novel glucagon analog as a therapeutic agent

    SciTech Connect

    Li, Pengyun; Rogers, Tanya; Smiley, David; DiMarchi, Richard D.; Zhang, Faming

    2007-07-01

    The synthesis and crystallization of glucagon-Cex are reported. Glucagon and glucagon-like peptide 1 (GLP-1) are drugs or drug candidates for the treatment of metabolic diseases such as diabetes and obesity. The native hormones have pharmacological deficiencies such as short half-life and poor solubility. A novel glucagon receptor agonist named glucagon-Cex has been designed, synthesized and crystallized. This peptide was highly soluble under physiological conditions and crystallized readily. The crystal diffracted X-rays to 2.2 Å resolution and the diffraction was consistent with space group P23, with unit-cell parameters a = b = c = 48.20 Å, α = β = γ = 90.0°. The crystals were suitable for a full structural determination to reveal the conformational differences between glucagon-Cex and the native hormone.

  1. Analog synthetic biology.

    PubMed

    Sarpeshkar, R

    2014-03-28

    We analyse the pros and cons of analog versus digital computation in living cells. Our analysis is based on fundamental laws of noise in gene and protein expression, which set limits on the energy, time, space, molecular count and part-count resources needed to compute at a given level of precision. We conclude that analog computation is significantly more efficient in its use of resources than deterministic digital computation even at relatively high levels of precision in the cell. Based on this analysis, we conclude that synthetic biology must use analog, collective analog, probabilistic and hybrid analog-digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets. We present schematics for efficiently representing analog DNA-protein computation in cells. Analog electronic flow in subthreshold transistors and analog molecular flux in chemical reactions obey Boltzmann exponential laws of thermodynamics and are described by astoundingly similar logarithmic electrochemical potentials. Therefore, cytomorphic circuits can help to map circuit designs between electronic and biochemical domains. We review recent work that uses positive-feedback linearization circuits to architect wide-dynamic-range logarithmic analog computation in Escherichia coli using three transcription factors, nearly two orders of magnitude more efficient in parts than prior digital implementations.

  2. Design of a hydraulic analog of the circulatory system for evaluating artificial hearts.

    PubMed

    Donovan, F M

    1975-01-01

    A major problem in improving artificial heart designs is the absence of methods for accurate in vitro testing of artificial heart systems. A mock circulatory system has been constructed which hydraulically simulates the systemic and pulmonary circulations of the normal human. The device is constructed of 1/2 in. acrylic sheet and has overall dimensions of 24 in. wide, 16 in. tall, and 8 in. deep. The artificial heart to be tested is attached to the front of the device, and pumps fluid from the systemic venous chamber into the pulmonary arterial chamber and from the pulmonary venous chamber into the systemic arterial chamber. Each of the four chambers is hermetically sealed. The compliance of each chamber is determined by the volume of air trapped above the fluid in that chamber. The pulmonary and systemic resistances are set automatically by bellows-operated valves to simulate the barroreceptor response in the systemic arteries and the passive pulmonary resistance response in the pulmonary arteries. Cardiac output is measured by a turbine flowmeter in the systemic circulation. Results using the Kwan-Gett artificial heart show a good comparison between the mock circulatory system response and the calf response.

  3. Extending analog design scaling to sub-wavelength lithography: co-optimization of RET and photomasks

    NASA Astrophysics Data System (ADS)

    Parikh, Ashesh; Dorris, Siew; Smelko, Tom; Walbrick, Walter; Mahalingam, Pushpa; Arch, John; Green, Kent; Garg, Vishal; Buck, Peter; West, Craig

    2011-04-01

    The mask requirements for 110nm half-node BiCMOS process were analyzed with the goal to meet customer needs at lower cost and shorter cycle times. The key differentiating features for this technology were high density CMOS libraries along with high-power Bipolar, LDMOS and DECMOS components. The high voltage components were characterized by transistors that formed cylindrical junctions. The presence of curved features in the data is particularly detrimental to the write time on a 50KeV vector mask writer. The mask write times have a direct impact on both mask cost and cycle time. Design rules also permit rectangular or stretched contacts to allow conductance of high currents. To meet customer needs but still manage the computational lithography overhead as well as the patterning process performance, this process was evaluated in terms of computational lithography and photomask co-optimization for the base-line 50KeV vector and laser mask-writers. Due to the differences in imaging and processing of the different mask writing systems, comparative analysis of critical dimension (CD) performance both in terms of linearity and pitch was done. Differences in imaging on silicon due to mask fidelity were also expected and characterized. The required changes in OPC necessary to switch to the new mask process were analyzed.

  4. Recent Advances in Nucleic Acid Binding Aspects of Berberine Analogs and Implications for Drug Design.

    PubMed

    Bhowmik, Debipreeta; Kumar, Gopinatha Suresh

    2016-01-01

    Berberine is one of the most widely known alkaloids belonging to the protoberberine group exhibiting myriad therapeutic properties. The anticancer potency of berberine appears to derive from its multiple actions including strong interaction with nucleic acids exhibiting adenine-thymine base pair specificity, inhibition of the enzymes topoisomerases and telomerases, and stabilizing the quadruplex structures. It was realized that the development of berberine as a potential anticancer agent necessitates enhancing its nucleic acid binding efficacy through appropriate structural modifications. More recently a number of such approaches have been attempted in various laboratories with great success. Several derivatives have been synthesized mostly with substitutions at the 8, 9 and 13 positions of the isoquinoline chromophore, and studied for enhanced nucleic acid binding activity. In this article, we present an up to date review of the details of the interaction of berberine and several of its important synthetic 8, 9 and 13 substituted derivatives with various nucleic acid structures reported recently. These studies provide interesting knowledge on the mode, mechanism, sequence and structural specificity of the binding of berberine derivatives and correlate structural and energetic aspects of the interaction providing better understanding of the structure- activity relations for designing and development of berberine based therapeutic agents with higher efficacy and therapeutic potential.

  5. Rational design of triazololipopeptides analogs of kisspeptin inducing a long-lasting increase of gonadotropins.

    PubMed

    Beltramo, Massimiliano; Robert, Vincent; Galibert, Mathieu; Madinier, Jean-Baptiste; Marceau, Philippe; Dardente, Hugues; Decourt, Caroline; De Roux, Nicolas; Lomet, Didier; Delmas, Agnès F; Caraty, Alain; Aucagne, Vincent

    2015-04-23

    New potent and selective KISS1R agonists were designed using a combination of rational chemical modifications of the endogenous neuropeptide kisspeptin 10 (KP10). Improved resistance to degradation and presumably reduced renal clearance were obtained by introducing a 1,4-disubstituted 1,2,3-triazole as a proteolysis-resistant amide mimic and a serum albumin-binding motif, respectively. These triazololipopeptides are highly potent full agonists of KISS1R and are >100 selective over the closely related NPFF1R. When injected in ewes with a quiescent reproductive system, the best compound of our series induced a much prolonged increase of luteinizing hormone release compared to KP10 and increased follicle-stimulating hormone plasma concentration. Hence, this KISS1R agonist is a new valuable pharmacological tool to explore the potential of KP system in reproduction control. Furthermore, it represents the first step to develop drugs treating reproductive system disorders due to a reduced activity of the hypothalamo-pituitary-gonadal axis such as delayed puberty, hypothalamic amenorrhea, and hypogonadotropic hypogonadism.

  6. Positive impression management and its influence on the Revised NEO Personality Inventory: a comparison of analog and differential prevalence group designs.

    PubMed

    Bagby, R Michael; Marshall, Margarita B

    2003-09-01

    Participants (n = 22) completed the Revised NEO Personality Inventory (NEO PI-R) as part of an authentic job application. Protocols produced by this group were compared with "analog" participants (n = 23) who completed the NEO PI-R under standard instructions and again under instructions designed to mimic the test-taking scenario of the job applicants (the "fake-good" condition). Participants completing the NEO PI-R under fake-good instructions and the job applicants scored lower on the Neuroticism and higher on the Extraversion scales than did the participants responding under standard instructions. Analog participants in the fake-good condition scored higher on the Extraversion and lower on the Agreeableness scales than did the job applicants. These results suggest that outcomes from analog designs are generalizable to real-world samples where response dissimulation is probable.

  7. An analog integrated circuit beamformer for high-frequency medical ultrasound imaging.

    PubMed

    Gurun, Gokce; Zahorian, Jaime S; Sisman, Alper; Karaman, Mustafa; Hasler, Paul E; Degertekin, F Levent

    2012-10-01

    We designed and fabricated a dynamic receive beamformer integrated circuit (IC) in 0.35-μm CMOS technology. This beamformer IC is suitable for integration with an annular array transducer for high-frequency (30-50 MHz) intravascular ultrasound (IVUS) imaging. The beamformer IC consists of receive preamplifiers, an analog dynamic delay-and-sum beamformer, and buffers for 8 receive channels. To form an analog dynamic delay line we designed an analog delay cell based on the current-mode first-order all-pass filter topology, as the basic building block. To increase the bandwidth of the delay cell, we explored an enhancement technique on the current mirrors. This technique improved the overall bandwidth of the delay line by a factor of 6. Each delay cell consumes 2.1-mW of power and is capable of generating a tunable time delay between 1.75 ns to 2.5 ns. We successfully integrated the fabricated beamformer IC with an 8-element annular array. Experimental test results demonstrated the desired buffering, preamplification and delaying capabilities of the beamformer.

  8. To Design or Not to Design (Part Five): Doctrine and Design: How Analogies and Design Theory Resist the Military Ritual of Codification

    DTIC Science & Technology

    2011-04-15

    discipline and reduce academic discourse. “Rather than getting a continuous and coherent picture, we are getting fragments- remarkably detailed but...Students that merely plagiarize by imitating existing successful designs do not learn, while students that combine novel creativity with

  9. Design, synthesis and biological evaluation of 3'-benzylated analogs of 3'-epi-neoponkoranol as potent α-glucosidase inhibitors.

    PubMed

    Liu, Dan; He, Weigang; Wang, Zihao; Liu, Long; Wang, Chengqian; Zhang, Chenxi; Wang, Chengcheng; Wang, Yuxuan; Tanabe, Genzoh; Muraoka, Osamu; Wu, Xiaoming; Wu, Liang; Xie, Weijia

    2016-03-03

    A group of 3'-epi-neoponkoranol analogs with different hydrophobic substituents attached at 3'-position of side chain moiety were designed and synthesized in order to further improve the inhibitory activities against α-glucosidases. Biological evaluation of these compounds revealed that sulfonium salts attached with ortho-substituted benzyl groups showed best α-glucosidase inhibitory activities. The most potent compound 10i showed greater inhibitory activities than all natural products. Moreover, docking studies on 10i with ntMGAM presented a new binding mode, indicating that amino residue Asp542 should be the key interacting point for strong inhibitory activity of small molecules against α-glucosidase enzymes. The strongest α-glucosidase inhibitory activity of 10i could be rationalized by van der Waals interactions between the 3'-attached substituent and particularly the ortho-substituted trifluoromethyl on benzyl group with the adjacent hydrophobic amino residues. Cytotoxicity evaluation assay demonstrated a high level of safety profile of the synthesized sulfonium salts against normal cell line. The enzyme kinetic studies showed a fully competitive inhibition of these sulfonium salts on each α-glucosidase.

  10. Frequency domain near-infrared multiwavelength imager design using high-speed, direct analog-to-digital conversion

    PubMed Central

    Zimmermann, Bernhard B.; Fang, Qianqian; Boas, David A.; Carp, Stefan A.

    2016-01-01

    Abstract. Frequency domain near-infrared spectroscopy (FD-NIRS) has proven to be a reliable method for quantification of tissue absolute optical properties. We present a full-sampling direct analog-to-digital conversion FD-NIR imager. While we developed this instrument with a focus on high-speed optical breast tomographic imaging, the proposed design is suitable for a wide-range of biophotonic applications where fast, accurate quantification of absolute optical properties is needed. Simultaneous dual wavelength operation at 685 and 830 nm is achieved by concurrent 67.5 and 75 MHz frequency modulation of each laser source, respectively, followed by digitization using a high-speed (180  MS/s) 16-bit A/D converter and hybrid FPGA-assisted demodulation. The instrument supports 25 source locations and features 20 concurrently operating detectors. The noise floor of the instrument was measured at <1.4  pW/√Hz, and a dynamic range of 115+ dB, corresponding to nearly six orders of magnitude, has been demonstrated. Titration experiments consisting of 200 different absorption and scattering values were conducted to demonstrate accurate optical property quantification over the entire range of physiologically expected values. PMID:26813081

  11. An investigation of the validity of the MMPI-2 response bias scale using an analog simulation design.

    PubMed

    Sullivan, Karen A; Elliott, Cameron

    2012-01-01

    This study evaluated a measure of feigned cognitive symptoms, the MMPI-2 Response Bias Scale (RBS), using an analog simulation design. A total of 81 participants were randomly allocated to one of two conditions: simulation (n = 40) or control (n = 41). Simulators were instructed to feign memory impairment. All participants completed an abbreviated form of the MMPI-2, Warrington's Word Recognition Memory test, and the Test of Memory Malingering. MMPI-2 data were used to calculate the RBS, F, K. FBS scores were prorated. Significant group differences were found on all measures. The effect size of group differences was largest for the RBS (d = 2.52) compared to the prorated FBS (d = 2.11), F (d = 1.31), and K (d = 0.85). Despite strong significant correlations between MMPI-2 scores, the RBS added incrementally to the other validity indicators in the prediction of group membership. The results from this RBS simulation study are consistent with several previous known-groups evaluations, which suggest that this scale is a useful indicator of negative response bias associated with exaggerated memory impairment.

  12. Frequency domain near-infrared multiwavelength imager design using high-speed, direct analog-to-digital conversion

    NASA Astrophysics Data System (ADS)

    Zimmermann, Bernhard B.; Fang, Qianqian; Boas, David A.; Carp, Stefan A.

    2016-01-01

    Frequency domain near-infrared spectroscopy (FD-NIRS) has proven to be a reliable method for quantification of tissue absolute optical properties. We present a full-sampling direct analog-to-digital conversion FD-NIR imager. While we developed this instrument with a focus on high-speed optical breast tomographic imaging, the proposed design is suitable for a wide-range of biophotonic applications where fast, accurate quantification of absolute optical properties is needed. Simultaneous dual wavelength operation at 685 and 830 nm is achieved by concurrent 67.5 and 75 MHz frequency modulation of each laser source, respectively, followed by digitization using a high-speed (180 MS/s) 16-bit A/D converter and hybrid FPGA-assisted demodulation. The instrument supports 25 source locations and features 20 concurrently operating detectors. The noise floor of the instrument was measured at <1.4 pW/√Hz, and a dynamic range of 115+ dB, corresponding to nearly six orders of magnitude, has been demonstrated. Titration experiments consisting of 200 different absorption and scattering values were conducted to demonstrate accurate optical property quantification over the entire range of physiologically expected values.

  13. A library of analog operators based on the hodgkin-huxley formalism for the design of tunable, real-time, silicon neurons.

    PubMed

    Saïghi, S; Bornat, Y; Tomas, J; Le Masson, G; Renaud, S

    2011-02-01

    In this paper, we present a library of analog operators used for the analog real-time computation of the Hodgkin-Huxley formalism. These operators make it possible to design a silicon (Si) neuron that is dynamically tunable, and that reproduces different kinds of neurons. We used an original method in neuromorphic engineering to characterize this Si neuron. In electrophysiology, this method is well known as the "voltage-clamp" technique. We also compare the features of an application-specific integrated circuit built with this library with results obtained from software simulations. We then present the complex behavior of neural membrane voltages and the potential applications of this Si neuron.

  14. Irregular Dwarf Galaxy IC 1613

    NASA Technical Reports Server (NTRS)

    2005-01-01

    Ultraviolet image (left) and visual image (right) of the irregular dwarf galaxy IC 1613. Low surface brightness galaxies, such as IC 1613, are more easily detected in the ultraviolet because of the low background levels compared to visual wavelengths.

  15. Analog synthetic biology

    PubMed Central

    Sarpeshkar, R.

    2014-01-01

    We analyse the pros and cons of analog versus digital computation in living cells. Our analysis is based on fundamental laws of noise in gene and protein expression, which set limits on the energy, time, space, molecular count and part-count resources needed to compute at a given level of precision. We conclude that analog computation is significantly more efficient in its use of resources than deterministic digital computation even at relatively high levels of precision in the cell. Based on this analysis, we conclude that synthetic biology must use analog, collective analog, probabilistic and hybrid analog–digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets. We present schematics for efficiently representing analog DNA–protein computation in cells. Analog electronic flow in subthreshold transistors and analog molecular flux in chemical reactions obey Boltzmann exponential laws of thermodynamics and are described by astoundingly similar logarithmic electrochemical potentials. Therefore, cytomorphic circuits can help to map circuit designs between electronic and biochemical domains. We review recent work that uses positive-feedback linearization circuits to architect wide-dynamic-range logarithmic analog computation in Escherichia coli using three transcription factors, nearly two orders of magnitude more efficient in parts than prior digital implementations. PMID:24567476

  16. Design, structural and functional characterization of a Temporin-1b analog active against Gram-negative bacteria.

    PubMed

    Avitabile, Concetta; Netti, Fortuna; Orefice, Giuseppina; Palmieri, Maddalena; Nocerino, Nunzia; Malgieri, Gaetano; D'Andrea, Luca D; Capparelli, Rosanna; Fattorusso, Roberto; Romanelli, Alessandra

    2013-06-01

    Temporins are small antimicrobial peptides secreted by the Rana temporaria showing mainly activity against Gram-positive bacteria. However, different members of the temporin family, such as Temporin B, act in synergy also against Gram-negative bacteria. With the aim to develop a peptide with a wide spectrum of antimicrobial activity we designed and analyzed a series of Temporin B analogs. Peptides were initially obtained by Ala scanning on Temporin B sequence; antimicrobial activity tests allowed to identify the TB_G6A sequence, which was further optimized by increasing the peptide positive charge (TB_KKG6A). Interactions of this active peptide with the LPS of E. coli were investigated by CD, fluorescence and NMR. TB_KKG6A is active against Gram-positive and Gram-negative bacteria at low concentrations. The peptide strongly interacts with the LPS of Gram-negative bacteria and folds upon interaction into a kinked helix. Our results show that it is possible to widen the activity spectrum of an antimicrobial peptide by subtle changes of the primary structure. TB_KKG6A, having a simple composition, a broad spectrum of antimicrobial activity and a very low hemolytic activity, is a promising candidate for the design of novel antimicrobial peptides. The activity of antimicrobial peptides is strongly related to the ability of the peptide to interact and break the bacterial membrane. Our studies on TB_KKG6A indicate that efficient interactions with LPS can be achieved when the peptide is not perfectly amphipathic, since this feature seems to help the toroidal pore formation process. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Design new P-glycoprotein modulators based on molecular docking and CoMFA study of α, β-unsaturated carbonyl-based compounds and oxime analogs as anticancer agents

    NASA Astrophysics Data System (ADS)

    Sepehri, Bakhtyar; Ghavami, Raouf

    2017-02-01

    In this research, molecular docking and CoMFA were used to determine interactions of α, β-unsaturated carbonyl-based compounds and oxime analogs with P-glycoprotein and prediction of their activity. Molecular docking study shown these molecules establish strong Van der Waals interactions with side chain of PHE-332, PHE-728 and PHE-974. Based on the effect of component numbers on squared correlation coefficient for cross validation tests (including leave-one-out and leave-many-out), CoMFA models with five components were built to predict pIC50 of molecules in seven cancer cell lines (including Panc-1 (pancreas cancer cell line), PaCa-2 (pancreatic carcinoma cell line), MCF-7 (breast cancer cell line), A-549 (epithelial), HT-29 (colon cancer cell line), H-460 (lung cancer cell line), PC-3 (prostate cancer cell line)). R2 values for training and test sets were in the range of 0.94-0.97 and 0.84 to 0.92, respectively, and for LOO and LMO cross validation test, q2 values were in the range of 0.75-0.82 and 0.65 to 0.73, respectively. Based on molecular docking results and extracted steric and electrostatic contour maps for CoMFA models, four new molecules with higher activity with respect to the most active compound in data set were designed.

  18. The Magnetics Information Consortium (MagIC)

    NASA Astrophysics Data System (ADS)

    Johnson, C.; Constable, C.; Tauxe, L.; Koppers, A.; Banerjee, S.; Jackson, M.; Solheid, P.

    2003-12-01

    analysis in the magnetic studies. Integration with these existing components will guarantee direct traceability to the original sources of the MagIC data and metadata. The MagIC database design focuses around the general workflow that results in the determination of typical paleomagnetic and rock magnetic analyses. This ensures that individual data points can be traced between the actual measurements and their associated specimen, sample, site, rock formation and locality. This permits a distinction between original and derived data, where the actual measurements are performed at the specimen level, and data at the sample level and higher are then derived products in the database. These relations will also allow recalculation of derived properties, such as site means, when new data becomes available for a specific locality. Data contribution to the MagIC database is critical in achieving a useful research tool. We have developed a standard data and metadata template that can be used to provide all data at the same time as publication. Software tools are provided to facilitate easy population of these templates. The tools allow for the import/export of data files in a delimited text format, and they provide some advanced functionality to validate data and to check internal coherence of the data in the template. During and after publication these standardized MagIC templates will be stored in the ERR database of EarthRef.org from where they can be downloaded at all times. Finally, the contents of these template files will be automatically parsed into the online relational database.

  19. Design and characterization of a fluorescent ghrelin analog for imaging the growth hormone secretagogue receptor 1a.

    PubMed

    McGirr, Rebecca; McFarland, Mark S; McTavish, Jillian; Luyt, Leonard G; Dhanvantari, Savita

    2011-12-10

    Ghrelin is a 28-amino acid peptide hormone produced in the stomach. It binds to the growth hormone secretagogue receptor 1a (GHS-R1a), a class A G-protein-coupled receptor. In the present study, we describe the design, synthesis and characterization of a truncated, 18-amino acid analog of ghrelin conjugated to a fluorescent molecule, fluorocein isothiocyanate (FITC), through the addition of a lysine at its C terminus ([Dpr(octanoyl)(3), Lys(fluorescein)(19)]ghrelin(1-19)). Receptor binding affinity of this novel fluorescein-ghrelin(1-18) was similar to that of wild-type ghrelin and a synthetic GHS-R1a ligand, hexarelin. Live cell imaging in CHO/GHS-R1a cells demonstrated cell surface receptor labeling and internalization, and agonist activity of fluorescein-ghrelin(1-18) was confirmed by increased phosphorylation of ERK1/2. We also show that GHS-R1a protein is expressed primarily in the heart when compared to all other organs, suggesting high receptor density in the left ventricle. Finally, we demonstrate that fluorescein-ghrelin(1-18) binds specifically to heart tissue in situ, and its binding is displaced by both wt ghrelin and hexarelin. We have therefore developed a novel imaging probe, fluorescein-ghrelin(1-18), that can be used to image GHS-R1a in situ, for the purposes of investigating mechanisms of receptor trafficking or pharmacological agents that target GHS-R1a. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Design and characterization of a mixed-signal PCB for digital-to-analog conversion in a modular and scalable infrared scene projector

    NASA Astrophysics Data System (ADS)

    Benedict, Jacob

    Infra-red (IR) sensors have proven instrumental in a wide variety of fields from military to industrial applications. The proliferation of IR sensors has spawned an intense push for technologies that can test and calibrate the multitudes of IR sensors. One such technology, IR scene projection (IRSP), provides an inexpensive and safe method for the testing of IR sensor devices. Previous efforts have been conducted to develop IRSPs based on super-lattice light emitting diodes (SLEDS). A single-color 512x512 SLEDs system has been developed, produced, and tested as documented in Corey Lange's Master's thesis, and a GOMAC paper by Rodney McGee [1][2]. Current efforts are being undergone to develop a two-color 512x512 SLEDs system designated (TCSA). The following thesis discusses the design and implementation of a custom printed circuit board (PCB), known as the FMC 4DAC, that contains both analog and digital signals. Utilizing two 16-bit digital-to-analog converters (DAC) the purpose of the board is to provide four analog current output channels for driving the TCSA system to a maximum frame rate of 1 kHz. In addition, the board supports a scalable TCSA system architecture. Several copies of the board can be run in parallel to achieve a range of analog channels between 4 and 32.

  1. Structure-based design, synthesis and biological testing of etoposide analog epipodophyllotoxin-N-mustard hybrid compounds designed to covalently bind to topoisomerase II and DNA.

    PubMed

    Yadav, Arun A; Wu, Xing; Patel, Daywin; Yalowich, Jack C; Hasinoff, Brian B

    2014-11-01

    Drugs that target DNA topoisomerase II isoforms and alkylate DNA represent two mechanistically distinct and clinically important classes of anticancer drugs. Guided by molecular modeling and docking a series of etoposide analog epipodophyllotoxin-N-mustard hybrid compounds were designed, synthesized and biologically characterized. These hybrids were designed to alkylate nucleophilic protein residues on topoisomerase II and thus produce inactive covalent adducts and to also alkylate DNA. The most potent hybrid had a mean GI(50) in the NCI-60 cell screen 17-fold lower than etoposide. Using a variety of in vitro and cell-based assays all of the hybrids tested were shown to target topoisomerase II. A COMPARE analysis indicated that the hybrids had NCI 60-cell growth inhibition profiles matching both etoposide and the N-mustard compounds from which they were derived. These results supported the conclusion that the hybrids displayed characteristics that were consistent with having targeted both topoisomerase II and DNA. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Analog earthquakes

    SciTech Connect

    Hofmann, R.B.

    1995-09-01

    Analogs are used to understand complex or poorly understood phenomena for which little data may be available at the actual repository site. Earthquakes are complex phenomena, and they can have a large number of effects on the natural system, as well as on engineered structures. Instrumental data close to the source of large earthquakes are rarely obtained. The rare events for which measurements are available may be used, with modfications, as analogs for potential large earthquakes at sites where no earthquake data are available. In the following, several examples of nuclear reactor and liquified natural gas facility siting are discussed. A potential use of analog earthquakes is proposed for a high-level nuclear waste (HLW) repository.

  3. Dynamical Competition of IC-Industry Clustering from Taiwan to China

    NASA Astrophysics Data System (ADS)

    Tsai, Bi-Huei; Tsai, Kuo-Hui

    2009-08-01

    Most studies employ qualitative approach to explore the industrial clusters; however, few research has objectively quantified the evolutions of industry clustering. The purpose of this paper is to quantitatively analyze clustering among IC design, IC manufacturing as well as IC packaging and testing industries by using the foreign direct investment (FDI) data. The Lotka-Volterra system equations are first adopted here to capture the competition or cooperation among such three industries, thus explaining their clustering inclinations. The results indicate that the evolution of FDI into China for IC design industry significantly inspire the subsequent FDI of IC manufacturing as well as IC packaging and testing industries. Since IC design industry lie in the upstream stage of IC production, the middle-stream IC manufacturing and downstream IC packing and testing enterprises tend to cluster together with IC design firms, in order to sustain a steady business. Finally, Taiwan IC industry's FDI amount into China is predicted to cumulatively increase, which supports the industrial clustering tendency for Taiwan IC industry. Particularly, the FDI prediction of Lotka-Volterra model performs superior to that of the conventional Bass model after the forecast accuracy of these two models are compared. The prediction ability is dramatically improved as the industrial mutualism among each IC production stage is taken into account.

  4. An ultra low-power front-end IC for wearable health monitoring system.

    PubMed

    Yu-Pin Hsu; Zemin Liu; Hella, Mona M

    2016-08-01

    This paper presents a low-power front-end IC for wearable health monitoring systems. The IC, designed in a standard 0.13μm CMOS technology, fully integrates a low-noise analog front-end (AFE) to process the weak bio-signals, followed by an analog-to-digital converter (ADC) to digitize the extracted signals. An AC-coupled driving buffer, that interfaces between the AFE and the ADC is introduced to scale down the power supply of the ADC. The power consumption decreases by 50% compared to the case without power supply scaling. The AFE passes signals from 0.5Hz to 280Hz and from 0.7Hz to 160Hz with a simulated input referred noise of 1.6μVrms and achieves a maximum gain of 35dB/41dB respectively, with a noise-efficiency factor (NEF) of the AFE is 1. The 8-bit ADC achieves a simulated 7.96-bit resolution at 10KS/s sampling rate under 0.5V supply voltage. The overall system consumes only 0.86μW at dual supply voltages of 1V (AFE) and 0.5 V (ADC).

  5. Cyclic AMP Analog Blocks Kinase Activation by Stabilizing Inactive Conformation: Conformational Selection Highlights a New Concept in Allosteric Inhibitor Design*

    PubMed Central

    Badireddy, Suguna; Yunfeng, Gao; Ritchie, Mark; Akamine, Pearl; Wu, Jian; Kim, Choel W.; Taylor, Susan S.; Qingsong, Lin; Swaminathan, Kunchithapadam; Anand, Ganesh S.

    2011-01-01

    The regulatory (R) subunit of protein kinase A serves to modulate the activity of protein kinase A in a cAMP-dependent manner and exists in two distinct and structurally dissimilar, end point cAMP-bound “B” and C-subunit-bound “H”-conformations. Here we report mechanistic details of cAMP action as yet unknown through a unique approach combining x-ray crystallography with structural proteomics approaches, amide hydrogen/deuterium exchange and ion mobility mass spectrometry, applied to the study of a stereospecific cAMP phosphorothioate analog and antagonist((Rp)-cAMPS). X-ray crystallography shows cAMP-bound R-subunit in the B form but surprisingly the antagonist Rp-cAMPS-bound R-subunit crystallized in the H conformation, which was previously assumed to be induced only by C-subunit-binding. Apo R-subunit crystallized in the B form as well but amide exchange mass spectrometry showed large differences between apo, agonist and antagonist-bound states of the R-subunit. Further ion mobility reveals the apo R-subunit as an ensemble of multiple conformations with collisional cross-sectional areas spanning both the agonist and antagonist-bound states. Thus contrary to earlier studies that explained the basis for cAMP action through “induced fit” alone, we report evidence for conformational selection, where the ligand-free apo form of the R-subunit exists as an ensemble of both B and H conformations. Although cAMP preferentially binds the B conformation, Rp-cAMPS interestingly binds the H conformation. This reveals the unique importance of the equatorial oxygen of the cyclic phosphate in mediating conformational transitions from H to B forms highlighting a novel approach for rational structure-based drug design. Ideal inhibitors such as Rp-cAMPS are those that preferentially “select” inactive conformations of target proteins by satisfying all “binding” constraints alone without inducing conformational changes necessary for activation. PMID:21081668

  6. Cyclic AMP analog blocks kinase activation by stabilizing inactive conformation: conformational selection highlights a new concept in allosteric inhibitor design.

    PubMed

    Badireddy, Suguna; Yunfeng, Gao; Ritchie, Mark; Akamine, Pearl; Wu, Jian; Kim, Choel W; Taylor, Susan S; Qingsong, Lin; Swaminathan, Kunchithapadam; Anand, Ganesh S

    2011-03-01

    The regulatory (R) subunit of protein kinase A serves to modulate the activity of protein kinase A in a cAMP-dependent manner and exists in two distinct and structurally dissimilar, end point cAMP-bound "B" and C-subunit-bound "H"-conformations. Here we report mechanistic details of cAMP action as yet unknown through a unique approach combining x-ray crystallography with structural proteomics approaches, amide hydrogen/deuterium exchange and ion mobility mass spectrometry, applied to the study of a stereospecific cAMP phosphorothioate analog and antagonist((Rp)-cAMPS). X-ray crystallography shows cAMP-bound R-subunit in the B form but surprisingly the antagonist Rp-cAMPS-bound R-subunit crystallized in the H conformation, which was previously assumed to be induced only by C-subunit-binding. Apo R-subunit crystallized in the B form as well but amide exchange mass spectrometry showed large differences between apo, agonist and antagonist-bound states of the R-subunit. Further ion mobility reveals the apo R-subunit as an ensemble of multiple conformations with collisional cross-sectional areas spanning both the agonist and antagonist-bound states. Thus contrary to earlier studies that explained the basis for cAMP action through "induced fit" alone, we report evidence for conformational selection, where the ligand-free apo form of the R-subunit exists as an ensemble of both B and H conformations. Although cAMP preferentially binds the B conformation, Rp-cAMPS interestingly binds the H conformation. This reveals the unique importance of the equatorial oxygen of the cyclic phosphate in mediating conformational transitions from H to B forms highlighting a novel approach for rational structure-based drug design. Ideal inhibitors such as Rp-cAMPS are those that preferentially "select" inactive conformations of target proteins by satisfying all "binding" constraints alone without inducing conformational changes necessary for activation.

  7. Hybrid IC / Microfluidic Chips for the Manipulation of Biological Cells

    NASA Astrophysics Data System (ADS)

    Lee, Hakho

    2005-03-01

    A hybrid IC / Microfluidic chip that can manipulate individual biological cells in a fluid with microscopic resolution has been demonstrated. The chip starts with a custom-designed silicon integrated circuit (IC) produced in a foundry using standard processing techniques. A microfluidic chamber is then fabricated on top of the IC to provide a biocompatible environment. The motion of biological cells in the chamber is controlled using a two-dimensional array of micro-scale electromagnets in the IC that generate spatially patterned magnetic fields. A local peak in the magnetic field amplitude will trap a magnetic bead and an attached cell; by moving the peak's location, the bead-bound cell can be moved to any position on the chip surface above the array. By generating multiple peaks, many cells can be moved independently along separate paths, allowing many different manipulations of individual cells. The hybrid IC / Microfluidic chip can be used, for example, to sort cells or to assemble tissue on micrometer length scales. To prove the concept, an IC / Microfluidic chip was fabricated, based on a custom-designed IC that contained a two-dimensional microcoil array with integrated current sources and control circuits. The chip was tested by trapping and moving biological cells tagged with magnetic beads inside the microfluidic chamber over the array. By combining the power of silicon technology with the biocompatibility of microfluidics, IC / Microfluidic chips will make new types of investigations possible in biological and biomedical studies.

  8. Extended red emission in IC59 and IC63

    NASA Astrophysics Data System (ADS)

    Lai, Thomas S.-Y.; Witt, Adolf N.; Crawford, Ken

    2017-08-01

    We analysed new wide-field, wide- and narrow-band optical images of IC 59 and IC 63, two nebulae that are externally illuminated by the early B-star γ Cas, with the objective of mapping the extended red emission (ERE), a dust-related photoluminescence process that is still poorly understood, in these two clouds. The spatial distribution of the ERE relative to the direction of the incident radiation and relative to other emission processes, whose carriers and excitation requirements are known, provides important constraints on the excitation of the ERE. In both nebulae, we find the ERE intensity to peak spatially well before the more extended distribution of mid-infrared emission in the unidentified infrared bands, supporting earlier findings that point towards far-ultraviolet (11 < Ephoton < 13.6 eV) photons as the source of ERE excitation. The band-integrated absolute intensities of the ERE in IC 59 and IC 63 measured relative to the number density of photons available for ERE excitation are lower by about two orders of magnitude compared to ERE intensities observed in the high-latitude diffuse interstellar medium. This suggests that the lifetime of the ERE carriers is significantly reduced in the more intense radiation field prevailing in IC 59 and IC 63, pointing towards potential carriers that are only marginally stable against photoprocessing under interstellar conditions. A model involving isolated molecules or molecular ions, capable of inverse internal conversion and recurrent fluorescence, appears to provide the most likely explanation for our observational results.

  9. The future through the past: The use of analog sites for design criteria and long-term performance assessment of evapotranspiration landfill covers.

    SciTech Connect

    David Shafer; Julianne Miller; Susan Edwards; Stuart Rawlinson

    2001-10-18

    There is growing support for using evapotranspiration (ET) covers for closure of low-level waste (LLW) and other types of waste disposal sites, particularly in the lower latitude arid regions of the western United States. For the Nevada Test Site (NTS), monolayer ET covers is the baseline technology for closure of LLW and mixed LLW cells. To better predict the long-term performance of monolayer ET covers, as well as to identify design criteria that will potentially improve their performance, the properties of, and processes occurring on, analog sites for ET covers on the NTS are being studied. Four analog sites on the NTS have been selected to predict performance of ET covers over a 1,000-year compliance period. Two are relatively recently disturbed sites (within the last 50 years) and have been selected for the evaluation of processes and changes on ET covers for the early period of post-institutional controls when cover maintenance would be discontinued. Two other sites, late to mid-Holocene in age, are intended as analogs for the end (1,000 years or more) of the compliance period. The late to mid-Holocene surfaces are both abandoned alluvial/colluvial deposits, dated by thermoluminescence analysis. The history of the early post-institutional control analog sites is being evaluated by an archaeologist to help determine when the sites were last disturbed or modified and the mode of disturbance, to help set baseline conditions. Similar to the other ''landforms,'' ET covers will evolve over time because of pedogenic, biotic, and climatic processes. Properties of analog sites that could affect ET water-balance performance will be evaluated to help understand ET cover performance over time. Results of analog site work and resultant modifications to design, monitoring and maintenance of ET covers on the NTS will be compared with results of a similar study being done at Sandia National Laboratories (SNL), where ET cover closures are planned as well. The comparison will

  10. The Future Through the Past: The Use of Analog Sites for Design Criteria and Long Term Performance Assessment of Evapotranspiration Landfill Covers

    SciTech Connect

    Shafer, D. S.; Miller, J. J.; Young, M. H.; Edwards, S. C.; Rawlinson, S. E.

    2002-02-26

    There is growing support for using evapotranspiration (ET) covers for closure of low-level waste (LLW) and other types of waste disposal sites, particularly in the lower latitude arid regions of the western United States. At the Nevada Test Site (NTS), monolayer ET covers are the baseline technology for closure of LLW and mixed LLW cells. To better predict the long-term performance of monolayer ET covers, as well as to identify design criteria that will potentially improve their performance, the properties of, and processes occurring on, analog sites for ET covers on the NTS are being studied. The project is funded through the Subsurface Contaminants Focus Area of the U.S. Department of Energy. Four analog sites on the NTS have been selected to predict performance of ET covers over a 1,000-year compliance period. Two sites are relatively recently disturbed (within the last 50 years) and have been selected to evaluate processes and changes on ET covers for the early period after active cover maintenance is discontinued. Two other sites, late to mid-Holocene in age, are intended as analogs for the end of the compliance period (1,000 years or more); both surfaces are abandoned alluvial/colluvial deposits. The history of the early post-institutional control analog sites are being evaluated by an archaeologist to help determine when the sites were last disturbed or modified, and the mode of disturbance to help set baseline conditions. Similar to other ''landforms,'' ET covers will evolve over time because of pedogenic, biotic, and climatic processes. Properties of analog sites that could affect ET water balance performance will be evaluated to help understand ET cover performance over time.

  11. Local environments of SNe Ic and Ic-BL

    NASA Astrophysics Data System (ADS)

    Selsing, Jonatan; Christensen, Lise; Thöne, Christina; Modjaz, Maryam

    2015-08-01

    In this project we have observed the local explosion environments of a sample Type Ic and Type Ic-BL Supernove (SNe) selected from both targeted and non-targeted surveys using VLT/VIMOS in IFU-mode. It is believed that by probing the local surroundings of the parent stellar populations of these types of SNe, valuable information can be gained about the physical conditions, which affect the type of SNe produced. The different kinds of SNe produced are determined by the initial mass and metallicity of the stellar progenitor, as well as by the metallicity-dependent mass loss in the stellar winds at the end phase of their evolution and the interaction with a sufficiently close companion star. At the redshift of the galaxies we have selected, we spatially resolve regions ~250 pc across, comparable to the size of HII regions in local galaxies and using strong nebular emission lines as a proxy for the metal content of the stellar population, we can investigate if the conditions for the two types of SNe differ. The connection between long-duration gamma-ray bursts (GRBs) and broad-lined SNe Ic and the existence of SNe Ic-bl without observed GRBs raises the question of what distinguishes a GRB progenitor from that of an ordinary SN Ic-bl without a GRB and this project will help with the elucidation of this. Moreover, from the HII region ages and stellar mass estimates, we examine the two suggested progenitor models for stripped SNe: single massive Wolf-Rayet (WR) stars with main-sequence masses of >30M⊙ that have experienced mass loss during the main sequence and WR stages, vs. binaries from lower-mass He stars.

  12. Design and synthesis of novel, potent and selective hypoxanthine analogs as adenosine A1 receptor antagonists and their biological evaluation.

    PubMed

    Koul, Summon; Ramdas, Vidya; Barawkar, Dinesh A; Waman, Yogesh B; Prasad, Neela; Madadi, Santosh Kumar; Shejul, Yogesh D; Bonagiri, Rajesh; Basu, Sujay; Menon, Suraj; Reddy, Srinivasa B; Chaturvedi, Sandhya; Chennamaneni, Srinivas Rao; Bedse, Gaurav; Thakare, Rhishikesh; Gundu, Jayasagar; Chaudhary, Sumit; De, Siddhartha; Meru, Ashwinkumar V; Palle, Venkata; Chugh, Anita; Mookhtiar, Kasim A

    2017-03-15

    Multipronged approach was used to synthesize a library of diverse C-8 cyclopentyl hypoxanthine analogs from a common intermediate III. Several potent and selective compounds were identified and evaluated for pharmacokinetic (PK) properties in Wistar rats. One of the compounds 14 with acceptable PK parameters was selected for testing in in vivo primary acute diuresis model. The compound demonstrated significant diuretic activity in this model.

  13. Analogical scaffolding: Making meaning in physics through representation and analogy

    NASA Astrophysics Data System (ADS)

    Podolefsky, Noah Solomon

    This work reviews the literature on analogy, introduces a new model of analogy, and presents a series of experiments that test and confirm the utility of this model to describe and predict student learning in physics with analogy. Pilot studies demonstrate that representations (e.g., diagrams) can play a key role in students' use of analogy. A new model of analogy, Analogical Scaffolding, is developed to explain these initial empirical results. This model will be described in detail, and then applied to describe and predict the outcomes of further experiments. Two large-scale (N>100) studies will demonstrate that: (1) students taught with analogies, according to the Analogical Scaffolding model, outperform students taught without analogies on pre-post assessments focused on electromagnetic waves; (2) the representational forms used to teach with analogy can play a significant role in student learning, with students in one treatment group outperforming students in other treatment groups by factors of two or three. It will be demonstrated that Analogical Scaffolding can be used to predict these results, as well as finer-grained results such as the types of distracters students choose in different treatment groups, and to describe and analyze student reasoning in interviews. Abstraction in physics is reconsidered using Analogical Scaffolding. An operational definition of abstraction is developed within the Analogical Scaffolding framework and employed to explain (a) why physicists consider some ideas more abstract than others in physics, and (b) how students conceptions of these ideas can be modeled. This new approach to abstraction suggests novel approaches to curriculum design in physics using Analogical Scaffolding.

  14. Antibacterial and Antibiofilm Activities of Makaluvamine Analogs

    PubMed Central

    Nijampatnam, Bhavitavya; Nadkarni, Dwayaja H.; Wu, Hui; Velu, Sadanandan E.

    2014-01-01

    Streptococcus mutans is a key etiological agent in the formation of dental caries. The major virulence factor is its ability to form biofilms. Inhibition of S. mutans biofilms offers therapeutic prospects for the treatment and the prevention of dental caries. In this study, 14 analogs of makaluvamine, a marine alkaloid, were evaluated for their antibacterial activity against S. mutans and for their ability to inhibit S. mutans biofilm formation. All analogs contained the tricyclic pyrroloiminoquinone core of makaluvamines. The structural variations of the analogs are on the amino substituents at the 7-position of the ring and the inclusion of a tosyl group on the pyrrole ring N of the makaluvamine core. The makaluvamine analogs displayed biofilm inhibition with IC50 values ranging from 0.4 μM to 88 μM. Further, the observed bactericidal activity of the majority of the analogs was found to be consistent with the anti-biofilm activity, leading to the conclusion that the anti-biofilm activity of these analogs stems from their ability to kill S. mutans. However, three of the most potent N-tosyl analogs showed biofilm IC50 values at least an order of magnitude lower than that of bactericidal activity, indicating that the biofilm activity of these analogs is more selective and perhaps independent of bactericidal activity. PMID:25767719

  15. Triptycene analogs

    NASA Technical Reports Server (NTRS)

    Hua, Duy (Inventor); Perchellet, Jean-Pierre (Inventor)

    2004-01-01

    This invention provides analogs of triptycene which are useful as anticancer drugs, as well as for other uses. The potency of these compounds is in a similar magnitude as daunomycin, a currently used anticancer drug. Each compound of the invention produces one or more desired effects (blocking nucleoside transport, inhibiting nucleic acid or protein syntheses, decreasing the proliferation and viability of cancer cells, inducing DNA fragmentation or retaining their effectiveness against multidrug-resistant tumor cells).

  16. Reliability in CMOS IC processing

    NASA Technical Reports Server (NTRS)

    Shreeve, R.; Ferrier, S.; Hall, D.; Wang, J.

    1990-01-01

    Critical CMOS IC processing reliability monitors are defined in this paper. These monitors are divided into three categories: process qualifications, ongoing production workcell monitors, and ongoing reliability monitors. The key measures in each of these categories are identified and prioritized based on their importance.

  17. Young Stars in IC 2118

    NASA Astrophysics Data System (ADS)

    Spuck, Tim; Rebull, Luisa; Daou, Doris; Maranto, Tony; Roelofsen, Theresa; Sepulveda, Babs; Weehler, Cynthia

    2005-02-01

    IC 2118, the Witch Head Nebula (~210 parsecs), is region forming stars located near the supergiant star Rigel in the constellation Orion. Kun et al. (2004, A&A, 418, 89) have determined that IC 2118 is on the near side of the Orion-Eridanus Super Bubble and that stellar winds from the Orion OB1 association may be triggering new star formation in the nebula. We propose using IRAC and MIPS to reexamine a small dense region of this nebula where Kun et al. have spectroscopically identified three 2MASS sources as T Tauri stars embedded in the cloud. Previous all-sky surveys, including both IRAS and 2MASS, have included this region, but not to the resolution that Spitzer can provide, and there are few studies of this particular region in the literature. Our team proposes to use IRAC and MIPS observations to (1) investigate star formation, (2) look for likely cluster member stars with infrared excesses, and characterize this young star population by obtaining their colors and therefore estimates of masses and ages, (3) study the distribution of stars, their relationship to the ISM, and the possibilities of triggered star formation, (4) compare the young star population, distribution, and age to other similar sites of star formation, e.g., IC 1396 and (5) produce a dramatic image of the interstellar medium in the region surrounding IC 2118. Since this region is in the Orion constellation near the bright star Rigel, it provides additional appeal to students and the general public.

  18. Characterization of four new designer drugs, 5-chloro-NNEI, NNEI indazole analog, α-PHPP and α-POP, with 11 newly distributed designer drugs in illegal products.

    PubMed

    Uchiyama, Nahoko; Matsuda, Satoru; Kawamura, Maiko; Shimokawa, Yoshihiko; Kikura-Hanajiri, Ruri; Aritake, Kosuke; Urade, Yoshihiro; Goda, Yukihiro

    2014-10-01

    Our continuous survey of illegal products in Japan revealed the new distribution of 15 designer drugs. We identified four synthetic cannabinoids, i.e., NNEI (1), 5-fluoro-NNEI (2), 5-chloro-NNEI (3) and NNEI indazole analog (4), and seven cathinone derivatives, i.e., MPHP (5), α-PHPP (6), α-POP (7), 3,4-dimethoxy-α-PVP (8), 4-fluoro-α-PVP (9), α-ethylaminopentiophenone (10) and N-ethyl-4-methylpentedrone (11). We also determined LY-2183240 (12) and its 2'-isomer (13), which were reported to inhibit endocannabinoid uptake, a methylphenidate analog, 3,4-dichloromethylphenidate (14), and an MDA analog, 5-APDB (15). No chemical and pharmaceutical data for compounds 3, 4, 6 and 7 had been reported, making this the first report on these compounds.

  19. R&D100: IC ID

    SciTech Connect

    Hamlet, Jason; Pierson, Lyndon; Bauer, Todd

    2015-11-19

    Supply chain security to detect, deter, and prevent the counterfeiting of networked and stand-alone integrated circuits (ICs) is critical to cyber security. Sandia National Laboratory researchers have developed IC ID to leverage Physically Unclonable Functions (PUFs) and strong cryptographic authentication to create a unique fingerprint for each integrated circuit. IC ID assures the authenticity of ICs to prevent tampering or malicious substitution.

  20. R&D100: IC ID

    ScienceCinema

    Hamlet, Jason; Pierson, Lyndon; Bauer, Todd

    2016-07-12

    Supply chain security to detect, deter, and prevent the counterfeiting of networked and stand-alone integrated circuits (ICs) is critical to cyber security. Sandia National Laboratory researchers have developed IC ID to leverage Physically Unclonable Functions (PUFs) and strong cryptographic authentication to create a unique fingerprint for each integrated circuit. IC ID assures the authenticity of ICs to prevent tampering or malicious substitution.

  1. A survey of the parasitic effects and degradation mechanisms affecting the GaAs FET-based IC's: The first step for a technological evaluation

    NASA Astrophysics Data System (ADS)

    Dumas, J. M.

    1991-03-01

    Several parasitic effects which influence GaAs IC performance are reviewed. The main concerns include in bulk trap dependent parasitics such as back (side) gating, and surface induced parasitics such as gate-lag. How the basic understanding of these effects is taken into account in the design rules provided to designers is discussed. Major degradation mechanisms are briefly reviewed. Failure modes observed from high temperature lifetesting conditions are demonstrated to give optimistic median life values when compared with those obtained from low temperatures. Failure criteria are reviewed. In order to assess the effects penalizing the integration and lifetime for both analog and digital IC's, a first step qualification procedure is proposed. It is based on specific test vehicles, issued from Process Control Monitors (PCM) or from specially designed Technology Characterization Vehicles (TCV).

  2. Analog Optical Links

    NASA Astrophysics Data System (ADS)

    Cox, Charles H., III

    2004-05-01

    Unlike books that focus on the devices used in links, such as lasers and photodiodes, among others, this text focuses on the next level. It covers the collection of devices that form a link, how the individual device performance affects the link performance, or the reverse. Analog links are used for the distribution of cable TV signals, and in conveying the signals to and from antennas (so called antenna remoting). The design of analog links differs significantly from digital links which are primarily used in telecommunications.

  3. Caffeine analogs: biomedical impact.

    PubMed

    Daly, J W

    2007-08-01

    Caffeine, widely consumed in beverages, and many xanthine analogs have had a major impact on biomedical research. Caffeine and various analogs, the latter designed to enhance potency and selectivity toward specific biological targets, have played key roles in defining the nature and role of adenosine receptors, phosphodiesterases, and calcium release channels in physiological processes. Such xanthines and other caffeine-inspired heterocycles now provide important research tools and potential therapeutic agents for intervention in Alzheimer's disease, asthma, cancer, diabetes, and Parkinson's disease. Such compounds also have activity as analgesics, antiinflammatories, antitussives, behavioral stimulants, diuretics/natriuretics, and lipolytics. Adverse effects can include anxiety, hypertension, certain drug interactions, and withdrawal symptoms.

  4. Low-Power Analog Processing for Sensing Applications: Low-Frequency Harmonic Signal Classification

    PubMed Central

    White, Daniel J.; William, Peter E.; Hoffman, Michael W.; Balkir, Sina

    2013-01-01

    A low-power analog sensor front-end is described that reduces the energy required to extract environmental sensing spectral features without using Fast Fouriér Transform (FFT) or wavelet transforms. An Analog Harmonic Transform (AHT) allows selection of only the features needed by the back-end, in contrast to the FFT, where all coefficients must be calculated simultaneously. We also show that the FFT coefficients can be easily calculated from the AHT results by a simple back-substitution. The scheme is tailored for low-power, parallel analog implementation in an integrated circuit (IC). Two different applications are tested with an ideal front-end model and compared to existing studies with the same data sets. Results from the military vehicle classification and identification of machine-bearing fault applications shows that the front-end suits a wide range of harmonic signal sources. Analog-related errors are modeled to evaluate the feasibility of and to set design parameters for an IC implementation to maintain good system-level performance. Design of a preliminary transistor-level integrator circuit in a 0.13 μm complementary metal-oxide-silicon (CMOS) integrated circuit process showed the ability to use online self-calibration to reduce fabrication errors to a sufficiently low level. Estimated power dissipation is about three orders of magnitude less than similar vehicle classification systems that use commercially available FFT spectral extraction. PMID:23892765

  5. Low-power analog processing for sensing applications: low-frequency harmonic signal classification.

    PubMed

    White, Daniel J; William, Peter E; Hoffman, Michael W; Balkir, Sina

    2013-07-25

    A low-power analog sensor front-end is described that reduces the energy required to extract environmental sensing spectral features without using Fast Fouriér Transform (FFT) or wavelet transforms. An Analog Harmonic Transform (AHT) allows selection of only the features needed by the back-end, in contrast to the FFT, where all coefficients must be calculated simultaneously. We also show that the FFT coefficients can be easily calculated from the AHT results by a simple back-substitution. The scheme is tailored for low-power, parallel analog implementation in an integrated circuit (IC). Two different applications are tested with an ideal front-end model and compared to existing studies with the same data sets. Results from the military vehicle classification and identification of machine-bearing fault applications shows that the front-end suits a wide range of harmonic signal sources. Analog-related errors are modeled to evaluate the feasibility of and to set design parameters for an IC implementation to maintain good system-level performance. Design of a preliminary transistor-level integrator circuit in a 0.13 µm complementary metal-oxide-silicon (CMOS) integrated circuit process showed the ability to use online self-calibration to reduce fabrication errors to a sufficiently low level. Estimated power dissipation is about three orders of magnitude less than similar vehicle classification systems that use commercially available FFT spectral extraction.

  6. Influence of Different Abutment Designs on the Biomechanical Behavior of Dental Root-Analog Implant: A Three-Dimensional Finite Element Analysis.

    PubMed

    He, Ling; Li, Deli; Zhang, Jiwu; Li, Xiucheng; Lu, Songhe; Tang, Zhihui

    2016-12-01

    The aim of this study was to evaluate cross-sectional area of the abutments, strain distribution in the periimplant bone, stress in the abutments and dental root-analog implant by different abutment design under different loading conditions, through three-dimensional finite element analysis. Two three-dimensional finite element models were established. Two types of abutments, oval cross section abutment (OCSA) and circular cross section abutment (CCSA) were designed, keeping the size of the thinnest implant wall 0.75 mm. Two types of load were applied to the abutment in each model: 100 N vertical load (V), 100 N vertical/50 N horizontal load (VH). The biomechanical behaviors of abutments, implants, and periimplant bone were recorded. The cross-section area of OCSA is 36.5% larger than that of CCSA. In implants, the maximum von Mises stress value in OCSA design was 24.6% lower than that in CCSA design under V and under VH. In abutments, the maximum von Mises stress value in OCSA design was 40.0% lower than that in CCSA design under V, the maximum von Mises stress value in OCSA design was 12.2% lower than that in CCSA design under VH. The irregular design offers advantages over regular design.

  7. Pressure generated on a simulated mandibular oral analog by impression materials in custom trays of different design.

    PubMed

    Al-Ahmad, Adel; Masri, Radi; Driscoll, Carl F; von Fraunhofer, Joseph; Romberg, Elaine

    2006-01-01

    The purpose was to measure the pressure exerted under a simulated mandibular edentulous impression at different locations using commonly used impression materials and four impression tray configurations. This study was performed using an oral analog that simulated an edentulous mandibular arch. Three pressure transducers were embedded in the oral analog-one pressure transducer in the anterior ridge area, and the other two in the right and left buccal shelves. Four configurations of custom trays were fabricated: trays with no relief, with and without holes; and trays with relief, with and without holes. The impression materials tested were light body polysulfide, light body vinyl polysiloxane, medium body vinyl polysiloxane, and irreversible hydrocolloid. The custom tray and the oral analog were mounted using a reline jig, and a Satec universal testing machine was used to apply a constant pressure of 1 kg/cm(2) over a period of 5 minutes on the loaded custom tray. Eighty impressions for the 16 groups (n = 5) were made, and pressures were recorded every 10 seconds. Factorial ANOVA and Tukey Multiple Comparison Test were used to analyze the results (p < 0.05). A significant difference was found in the pressure produced using different impression materials. Irreversible hydrocolloid and medium body vinyl polysiloxane produced significantly higher pressure than light body polysulfide and light body vinyl polysiloxane impression materials. The presence of holes and/or relief significantly altered the magnitude of pressure produced by irreversible hydrocolloid and medium body vinyl polysiloxane but not light body polysulfide and light body vinyl polysiloxane. All impression materials produced pressure during simulated mandibular edentulous impression making. For making mandibular edentulous impressions, low-viscosity impression materials-light body polysulfide and light body vinyl polysiloxane-are recommended. Tray modification was not important in changing the amount of

  8. Design, synthesis and biological evaluation of di-substituted noscapine analogs as potent and microtubule-targeted anticancer agents.

    PubMed

    Mishra, Ram C; Gundala, Sushma R; Karna, Prasanthi; Lopus, Manu; Gupta, Kamlesh K; Nagaraju, Mulpuri; Hamelberg, Donald; Tandon, Vibha; Panda, Dulal; Reid, Michelle D; Aneja, Ritu

    2015-01-01

    Noscapine is an opium-derived kinder-gentler microtubule-modulating drug, currently in Phase I/II clinical trials for cancer chemotherapy. Here, we report the synthesis of four more potent di-substituted brominated derivatives of noscapine, 9-Br-7-OH-NOS (2), 9-Br-7-OCONHEt-NOS (3), 9-Br-7-OCONHBn-NOS (4), and 9-Br-7-OAc-NOS (5) and their chemotherapeutic efficacy on PC-3 and MDA-MB-231 cells. The four derivatives were observed to have higher tubulin binding activity than noscapine and significantly affect tubulin polymerization. The equilibrium dissociation constant (KD) for the interaction between tubulin and 2, 3, 4, 5 was found to be, 55±6μM, 44±6μM, 26±3μM, and 21±1μM respectively, which is comparable to parent analog. The effects of these di-substituted noscapine analogs on cell cycle parameters indicate that the cells enter a quiescent phase without undergoing further cell division. The varying biological activity of these analogs and bulk of substituent at position-7 of the benzofuranone ring system of the parent molecule was rationalized utilizing predictive in silico molecular modeling. Furthermore, the immunoblot analysis of protein lysates from cells treated with 4 and 5, revealed the induction of apoptosis and down-regulation of survivin levels. This result was further supported by the enhanced activity of caspase-3/7 enzymes in treated samples compared to the controls. Hence, these compounds showed a great potential for studying microtubule-mediated processes and as chemotherapeutic agents for the management of human cancers.

  9. Design and Characterization of Long-Haul Single-Channel Intensity-Modulated Analog Fiber-Optic Links

    DTIC Science & Technology

    2005-09-29

    Williams, 蔾 km 256-QAM digital microwave over fiber link," in IEEE MTT-S Digest , Philadelphia, pp. 269-272, June 2003. [2] V. J. Urick, J. X. Qiu...IEEE MTT-S Digest , vol. 3, pp. 1691-1693, June 2002. [4] A. L. Campillo, F. Bucholtz, J. L. Dexter, and K. J. Williams, "Crosstalk reduction in...wavelength division multiplexed analog links through polarization modulation," in CLEO/IQEC & PhAST Technical Digest , San Francisco, paper CWQ3, May 2004. [5

  10. Configurable analog-digital conversion using the neural engineering framework

    PubMed Central

    Mayr, Christian G.; Partzsch, Johannes; Noack, Marko; Schüffny, Rene

    2014-01-01

    Efficient Analog-Digital Converters (ADC) are one of the mainstays of mixed-signal integrated circuit design. Besides the conventional ADCs used in mainstream ICs, there have been various attempts in the past to utilize neuromorphic networks to accomplish an efficient crossing between analog and digital domains, i.e., to build neurally inspired ADCs. Generally, these have suffered from the same problems as conventional ADCs, that is they require high-precision, handcrafted analog circuits and are thus not technology portable. In this paper, we present an ADC based on the Neural Engineering Framework (NEF). It carries out a large fraction of the overall ADC process in the digital domain, i.e., it is easily portable across technologies. The analog-digital conversion takes full advantage of the high degree of parallelism inherent in neuromorphic networks, making for a very scalable ADC. In addition, it has a number of features not commonly found in conventional ADCs, such as a runtime reconfigurability of the ADC sampling rate, resolution and transfer characteristic. PMID:25100933

  11. Configurable analog-digital conversion using the neural engineering framework.

    PubMed

    Mayr, Christian G; Partzsch, Johannes; Noack, Marko; Schüffny, Rene

    2014-01-01

    Efficient Analog-Digital Converters (ADC) are one of the mainstays of mixed-signal integrated circuit design. Besides the conventional ADCs used in mainstream ICs, there have been various attempts in the past to utilize neuromorphic networks to accomplish an efficient crossing between analog and digital domains, i.e., to build neurally inspired ADCs. Generally, these have suffered from the same problems as conventional ADCs, that is they require high-precision, handcrafted analog circuits and are thus not technology portable. In this paper, we present an ADC based on the Neural Engineering Framework (NEF). It carries out a large fraction of the overall ADC process in the digital domain, i.e., it is easily portable across technologies. The analog-digital conversion takes full advantage of the high degree of parallelism inherent in neuromorphic networks, making for a very scalable ADC. In addition, it has a number of features not commonly found in conventional ADCs, such as a runtime reconfigurability of the ADC sampling rate, resolution and transfer characteristic.

  12. Conceptual design of the TRACE detector readout using a compact, dead time-less analog memory ASIC

    NASA Astrophysics Data System (ADS)

    Aliaga, R. J.; Herrero-Bosch, V.; Capra, S.; Pullia, A.; Dueñas, J. A.; Grassi, L.; Triossi, A.; Domingo-Pardo, C.; Gadea, R.; González, V.; Hüyük, T.; Sanchís, E.; Gadea, A.; Mengoni, D.

    2015-11-01

    The new TRacking Array for light Charged particle Ejectiles (TRACE) detector system requires monitorization and sampling of all pulses in a large number of channels with very strict space and power consumption restrictions for the front-end electronics and cabling. Its readout system is to be based on analog memory ASICs with 64 channels each that sample a 1 μs window of the waveform of any valid pulses at 200 MHz while discarding any other signals and are read out at 50 MHz with external ADC digitization. For this purpose, a new, compact analog memory architecture is described that allows pulse capture with zero dead time in any channel while vastly reducing the total number of storage cells, particularly for large amounts of input channels. This is accomplished by partitioning the typical Switched Capacitor Array structure into two pipelined, asymmetric stages and introducing FIFO queue-like control circuitry for captured data, achieving total independence between the capture and readout operations.

  13. Intratumoral hu14.18-IL-2 (IC) induces local and systemic antitumor effects that involve both activated T and NK cells as well as enhanced IC retention.

    PubMed

    Yang, Richard K; Kalogriopoulos, Nicholas A; Rakhmilevich, Alexander L; Ranheim, Erik A; Seo, Songwon; Kim, Kyungmann; Alderson, Kory L; Gan, Jacek; Reisfeld, Ralph A; Gillies, Stephen D; Hank, Jacquelyn A; Sondel, Paul M

    2012-09-01

    hu14.18-IL-2 (IC) is an immunocytokine consisting of human IL-2 linked to hu14.18 mAb, which recognizes the GD2 disialoganglioside. Phase 2 clinical trials of i.v. hu14.18-IL-2 (i.v.-IC) in neuroblastoma and melanoma are underway and have already demonstrated activity in neuroblastoma. We showed previously that intratumoral hu14.18-IL-2 (IT-IC) results in enhanced antitumor activity in mouse models compared with i.v.-IC. The studies presented in this article were designed to determine the mechanisms involved in this enhanced activity and to support the future clinical testing of intratumoral administration of immunocytokines. Improved survival and inhibition of growth of both local and distant tumors were observed in A/J mice bearing s.c. NXS2 neuroblastomas treated with IT-IC compared with those treated with i.v.-IC or control mice. The local and systemic antitumor effects of IT-IC were inhibited by depletion of NK cells or T cells. IT-IC resulted in increased NKG2D receptors on intratumoral NKG2A/C/E⁺ NKp46⁺ NK cells and NKG2A/C/E⁺ CD8⁺ T cells compared with control mice or mice treated with i.v.-IC. NKG2D levels were augmented more in tumor-infiltrating lymphocytes compared with splenocytes, supporting the localized nature of the intratumoral changes induced by IT-IC treatment. Prolonged retention of IC at the tumor site was seen with IT-IC compared with i.v.-IC. Overall, IT-IC resulted in increased numbers of activated T and NK cells within tumors, better IC retention in the tumor, enhanced inhibition of tumor growth, and improved survival compared with i.v.-IC.

  14. Microwave Photonic Architecture for Direction Finding of LPI Emitters: Front End Analog Circuit Design and Component Characterization

    DTIC Science & Technology

    2016-09-01

    14  III.  INNOVATIVE SYSTEM DESIGN ....................................................................15  A.  RF...DF System from Previous Design . Source: [11].............11  Figure 3.  Improved Design of Photonics DF System ...obtain DF information in computing the AOA. The type of DF technique employed influences the complexity of system design , cost of construction, and

  15. An adaptive, dose-finding, seamless phase 2/3 study of a long-acting glucagon-like peptide-1 analog (dulaglutide): trial design and baseline characteristics.

    PubMed

    Geiger, Mary Jane; Skrivanek, Zachary; Gaydos, Brenda; Chien, Jenny; Berry, Scott; Berry, Donald

    2012-11-01

    Dulaglutide (dula, LY2189265) is a once-weekly glucagon-like peptide-1 analog in development for the treatment of type 2 diabetes mellitus. An adaptive, dose-finding, inferentially seamless phase 2/3 study was designed to support the development of this novel diabetes therapeutic. The study is divided into two stages based on two randomization schemes: a Bayesian adaptive scheme (stage 1) and a fixed scheme (stage 2). Stage 1 of the trial employs an adaptive, dose-finding design to lead to a dula dose-selection decision or early study termination due to futility. If dose selection occurs, the study proceeds to stage 2 to allow continued evaluation of the selected dula doses. At completion, the entire study will serve as a confirmatory phase 3 trial. The final study design is discussed, along with specifics pertaining to the actual execution of this study and selected baseline characteristics of the participants. © 2012 Diabetes Technology Society.

  16. Synthesis and Antimalarial Activities of Cyclen 4-Aminoquinoline Analogs

    USDA-ARS?s Scientific Manuscript database

    In an attempt to augment the efficacy of 7-chloro 4-aminoquinoline analogs and also to overcome resistance to anti-malarial agents we synthesized three cyclen analogs of chloroquine (4,6,7). Compound 4 displays the most potent in vitro and in vivo antimalarial activities. It displays an IC50 of 7.5 ...

  17. Structure-based design, synthesis, and biological evaluation of Leu-Arg dipeptide analogs as novel hepsin inhibitors.

    PubMed

    Kwon, Hongmok; Kim, YunHye; Park, Kieung; Choi, Soo An; Son, Sang-Hyun; Byun, Youngjoo

    2016-01-15

    Hepsin, a type II transmembrane serine protease, is an attractive protein as a potential therapeutic and diagnostic biomarker for prostate cancer because it is highly up-regulated in prostate cancer and promotes both progression and metastasis. Starting from the reported tetrapeptide hepsin inhibitor Ac-KQLR-ketothiazole (kt) (1), we investigated the minimal structural requirements for hepsin inhibitory activity by truncating amino acids at the N-terminus. The kt and ketobenzothiazole (kbt) dipeptide analogs Ac-LR-kt (3) and Ac-LR-kbt (15) were found to be potent hepsin inhibitors, exhibiting Ki values of 22nM and 3nM, respectively. The present work suggests that LR-containing dipeptide molecules could be useful as lead compounds for the development of novel hepsin inhibitors.

  18. Improvement of Organizational Performance and Instructional Design: An Analogy Based on General Principles of Natural Information Processing Systems

    ERIC Educational Resources Information Center

    Darabi, Aubteen; Kalyuga, Slava

    2012-01-01

    The process of improving organizational performance through designing systemic interventions has remarkable similarities to designing instruction for improving learners' performance. Both processes deal with subjects (learners and organizations correspondingly) with certain capabilities that are exposed to novel information designed for producing…

  19. Improvement of Organizational Performance and Instructional Design: An Analogy Based on General Principles of Natural Information Processing Systems

    ERIC Educational Resources Information Center

    Darabi, Aubteen; Kalyuga, Slava

    2012-01-01

    The process of improving organizational performance through designing systemic interventions has remarkable similarities to designing instruction for improving learners' performance. Both processes deal with subjects (learners and organizations correspondingly) with certain capabilities that are exposed to novel information designed for producing…

  20. Mathematical problem solving by analogy.

    PubMed

    Novick, L R; Holyoak, K J

    1991-05-01

    We report the results of 2 experiments and a verbal protocol study examining the component processes of solving mathematical word problems by analogy. College students first studied a problem and its solution, which provided a potential source for analogical transfer. Then they attempted to solve several analogous problems. For some problems, subjects received one of a variety of hints designed to reduce or eliminate the difficulty of some of the major processes hypothesized to be involved in analogical transfer. Our studies yielded 4 major findings. First, the process of mapping the features of the source and target problems and the process of adapting the source solution procedure for use in solving the target problem were clearly distinguished: (a) Successful mapping was found to be insufficient for successful transfer and (b) adaptation was found to be a major source of transfer difficulty. Second, we obtained direct evidence that schema induction is a natural consequence of analogical transfer. The schema was found to co-exist with the problems from which it was induced, and both the schema and the individual problems facilitated later transfer. Third, for our multiple-solution problems, the relation between analogical transfer and solution accuracy was mediated by the degree of time pressure exerted for the test problems. Finally, mathematical expertise was a significant predictor of analogical transfer, but general analogical reasoning ability was not. The implications of the results for models of analogical transfer and for instruction were considered.

  1. High-speed low-power analog ASICs for a 3D neuroprocessor

    NASA Astrophysics Data System (ADS)

    Duong, Tuan A.; Kemeny, Sabrina E.; Tran, Mua D.; Daud, Taher; Thakoor, Anilkumar P.

    1995-03-01

    A particularly challenging neural network application requiring high-speed and intensive image processing capability is target acquisition and discrimination. It requires spatio-temporal recognition of point and resolved targets at high speeds. A reconfigurable neural architecture may discriminate targets from clutter or classify targets once resolved. By mating a 64 X 64 pixel array infrared (IR) image sensor to a 3-D stack (cube) of 64 neural-net ICs along respective edges, every pixel would directly input to a neural network, thereby processing the information with full parallelism. However, the `cube' has to operate at 90 degree(s)K with < 250 nanoseconds signal processing speed and approximately 2 watts of power dissipation. Analog circuitry, where the spatially parallel input to the neural networks is also analog, would make this possible. Digital neural processing would require analog-to-digital converters on each IC, impractical with the power constraint. A versatile reconfigurable circuit is presented that offers a variety of neural architectures: multilayer perceptron, cascade backpropagation, and template matching with winner-take-all (WTA) circuitry. Special designs of analog neuron and synapse implemented in VLSI are presented which bear out high speed response both at room and low temperatures with synapse-neuron signal propagation times of approximately 100 ns.

  2. Design and development of a probe-based multiplexed multi-species absorption spectroscopy sensor for characterizing transient gas-parameter distributions in the intake systems of I.C. engines

    SciTech Connect

    Jatana, Gurneesh; Geckler, Sam; Koeberlein, David; Partridge, William

    2016-09-01

    We designed and developed a 4-probe multiplexed multi-species absorption spectroscopy sensor system for gas property measurements on the intake side of commercial multi-cylinder internal-combustion (I.C.) engines; the resulting cycle- and cylinder-resolved concentration, temperature and pressure measurements are applicable for assessing spatial and temporal variations in the recirculated exhaust gas (EGR) distribution at various locations along the intake gas path, which in turn is relevant to assessing cylinder charge uniformity, control strategies, and CFD models. Furthermore, the diagnostic is based on absorption spectroscopy and includes an H2O absorption system (utilizing a 1.39 m distributed feedback (DFB) diode laser) for measuring gas temperature, pressure, and H2O concentration, and a CO2 absorption system (utilizing a 2.7 m DFB laser) for measuring CO2 concentration. The various lasers, optical components and detectors were housed in an instrument box, and the 1.39- m and 2.7- m lasers were guided to and from the engine-mounted probes via optical fibers and hollow waveguides, respectively. The 5kHz measurement bandwidth allows for near-crank angle resolved measurements, with a resolution of 1.2 crank angle degrees at 1000 RPM. Our use of compact stainless steel measurement probes enables simultaneous multi-point measurements at various locations on the engine with minimal changes to the base engine hardware; in addition to resolving large-scale spatial variations via simultaneous multi-probe measurements, local spatial gradients can be resolved by translating individual probes. Along with details of various sensor design features and performance, we also demonstrate validation of the spectral parameters of the associated CO2 absorption transitions using both a multi-pass heated cell and the sensor probes.

  3. Design and development of a probe-based multiplexed multi-species absorption spectroscopy sensor for characterizing transient gas-parameter distributions in the intake systems of I.C. engines

    DOE PAGES

    Jatana, Gurneesh; Geckler, Sam; Koeberlein, David; ...

    2016-09-01

    We designed and developed a 4-probe multiplexed multi-species absorption spectroscopy sensor system for gas property measurements on the intake side of commercial multi-cylinder internal-combustion (I.C.) engines; the resulting cycle- and cylinder-resolved concentration, temperature and pressure measurements are applicable for assessing spatial and temporal variations in the recirculated exhaust gas (EGR) distribution at various locations along the intake gas path, which in turn is relevant to assessing cylinder charge uniformity, control strategies, and CFD models. Furthermore, the diagnostic is based on absorption spectroscopy and includes an H2O absorption system (utilizing a 1.39 m distributed feedback (DFB) diode laser) for measuring gasmore » temperature, pressure, and H2O concentration, and a CO2 absorption system (utilizing a 2.7 m DFB laser) for measuring CO2 concentration. The various lasers, optical components and detectors were housed in an instrument box, and the 1.39- m and 2.7- m lasers were guided to and from the engine-mounted probes via optical fibers and hollow waveguides, respectively. The 5kHz measurement bandwidth allows for near-crank angle resolved measurements, with a resolution of 1.2 crank angle degrees at 1000 RPM. Our use of compact stainless steel measurement probes enables simultaneous multi-point measurements at various locations on the engine with minimal changes to the base engine hardware; in addition to resolving large-scale spatial variations via simultaneous multi-probe measurements, local spatial gradients can be resolved by translating individual probes. Along with details of various sensor design features and performance, we also demonstrate validation of the spectral parameters of the associated CO2 absorption transitions using both a multi-pass heated cell and the sensor probes.« less

  4. Design and development of a probe-based multiplexed multi-species absorption spectroscopy sensor for characterizing transient gas-parameter distributions in the intake systems of I.C. engines

    SciTech Connect

    Jatana, Gurneesh; Geckler, Sam; Koeberlein, David; Partridge, William

    2016-09-01

    We designed and developed a 4-probe multiplexed multi-species absorption spectroscopy sensor system for gas property measurements on the intake side of commercial multi-cylinder internal-combustion (I.C.) engines; the resulting cycle- and cylinder-resolved concentration, temperature and pressure measurements are applicable for assessing spatial and temporal variations in the recirculated exhaust gas (EGR) distribution at various locations along the intake gas path, which in turn is relevant to assessing cylinder charge uniformity, control strategies, and CFD models. Furthermore, the diagnostic is based on absorption spectroscopy and includes an H2O absorption system (utilizing a 1.39 m distributed feedback (DFB) diode laser) for measuring gas temperature, pressure, and H2O concentration, and a CO2 absorption system (utilizing a 2.7 m DFB laser) for measuring CO2 concentration. The various lasers, optical components and detectors were housed in an instrument box, and the 1.39- m and 2.7- m lasers were guided to and from the engine-mounted probes via optical fibers and hollow waveguides, respectively. The 5kHz measurement bandwidth allows for near-crank angle resolved measurements, with a resolution of 1.2 crank angle degrees at 1000 RPM. Our use of compact stainless steel measurement probes enables simultaneous multi-point measurements at various locations on the engine with minimal changes to the base engine hardware; in addition to resolving large-scale spatial variations via simultaneous multi-probe measurements, local spatial gradients can be resolved by translating individual probes. Along with details of various sensor design features and performance, we also demonstrate validation of the spectral parameters of the associated CO2 absorption transitions using both a multi-pass heated cell and the sensor probes.

  5. Analogies: Explanatory Tools in Web-Based Science Instruction

    ERIC Educational Resources Information Center

    Glynn, Shawn M.; Taasoobshirazi, Gita; Fowler, Shawn

    2007-01-01

    This article helps designers of Web-based science instruction construct analogies that are as effective as those used in classrooms by exemplary science teachers. First, the authors explain what analogies are, how analogies foster learning, and what form analogies should take. Second, they discuss science teachers' use of analogies. Third, they…

  6. Analogies: Explanatory Tools in Web-Based Science Instruction

    ERIC Educational Resources Information Center

    Glynn, Shawn M.; Taasoobshirazi, Gita; Fowler, Shawn

    2007-01-01

    This article helps designers of Web-based science instruction construct analogies that are as effective as those used in classrooms by exemplary science teachers. First, the authors explain what analogies are, how analogies foster learning, and what form analogies should take. Second, they discuss science teachers' use of analogies. Third, they…

  7. Design of a Low-Light-Level Image Sensor with On-Chip Sigma-Delta Analog-to- Digital Conversion

    NASA Technical Reports Server (NTRS)

    Mendis, Sunetra K.; Pain, Bedabrata; Nixon, Robert H.; Fossum, Eric R.

    1993-01-01

    The design and projected performance of a low-light-level active-pixel-sensor (APS) chip with semi-parallel analog-to-digital (A/D) conversion is presented. The individual elements have been fabricated and tested using MOSIS* 2 micrometer CMOS technology, although the integrated system has not yet been fabricated. The imager consists of a 128 x 128 array of active pixels at a 50 micrometer pitch. Each column of pixels shares a 10-bit A/D converter based on first-order oversampled sigma-delta (Sigma-Delta) modulation. The 10-bit outputs of each converter are multiplexed and read out through a single set of outputs. A semi-parallel architecture is chosen to achieve 30 frames/second operation even at low light levels. The sensor is designed for less than 12 e^- rms noise performance.

  8. Design of a Low-Light-Level Image Sensor with On-Chip Sigma-Delta Analog-to- Digital Conversion

    NASA Technical Reports Server (NTRS)

    Mendis, Sunetra K.; Pain, Bedabrata; Nixon, Robert H.; Fossum, Eric R.

    1993-01-01

    The design and projected performance of a low-light-level active-pixel-sensor (APS) chip with semi-parallel analog-to-digital (A/D) conversion is presented. The individual elements have been fabricated and tested using MOSIS* 2 micrometer CMOS technology, although the integrated system has not yet been fabricated. The imager consists of a 128 x 128 array of active pixels at a 50 micrometer pitch. Each column of pixels shares a 10-bit A/D converter based on first-order oversampled sigma-delta (Sigma-Delta) modulation. The 10-bit outputs of each converter are multiplexed and read out through a single set of outputs. A semi-parallel architecture is chosen to achieve 30 frames/second operation even at low light levels. The sensor is designed for less than 12 e^- rms noise performance.

  9. Institutional computing (IC) information session

    SciTech Connect

    Koch, Kenneth R; Lally, Bryan R

    2011-01-19

    The LANL Institutional Computing Program (IC) will host an information session about the current state of unclassified Institutional Computing at Los Alamos, exciting plans for the future, and the current call for proposals for science and engineering projects requiring computing. Program representatives will give short presentations and field questions about the call for proposals and future planned machines, and discuss technical support available to existing and future projects. Los Alamos has started making a serious institutional investment in open computing available to our science projects, and that investment is expected to increase even more.

  10. A CMOS field-programmable analog array

    NASA Astrophysics Data System (ADS)

    Lee, Edward K. F.; Gulak, P. G.

    1991-12-01

    The design details and test results of a field-programmable analog array (FPAA) prototype chip in 1.2-micron CMOS are presented. The analog array is based on subthreshold circuit techniques and consists of a collection of a homogeneous configurable analog blocks (CABs) and an interconnection network. Interconnections between CABs and the analog functions to be implemented in each block are defined by a set of configuration bits loaded serially into an onboard shift register by the user. Macromodels are developed for the analog functions in order to simulate various neural network applications on the field-programmable analog array.

  11. SEM probe of IC radiation sensitivity

    NASA Technical Reports Server (NTRS)

    Gauthier, M. K.; Stanley, A. G.

    1979-01-01

    Scanning Electron Microscope (SEM) used to irradiate single integrated circuit (IC) subcomponent to test for radiation sensitivity can localize area of IC less than .03 by .03 mm for determination of exact location of radiation sensitive section.

  12. Analog storage integrated circuit

    DOEpatents

    Walker, J. T.; Larsen, R. S.; Shapiro, S. L.

    1989-01-01

    A high speed data storage array is defined utilizing a unique cell design for high speed sampling of a rapidly changing signal. Each cell of the array includes two input gates between the signal input and a storage capacitor. The gates are controlled by a high speed row clock and low speed column clock so that the instantaneous analog value of the signal is only sampled and stored by each cell on coincidence of the two clocks.

  13. Analog storage integrated circuit

    DOEpatents

    Walker, J.T.; Larsen, R.S.; Shapiro, S.L.

    1989-03-07

    A high speed data storage array is defined utilizing a unique cell design for high speed sampling of a rapidly changing signal. Each cell of the array includes two input gates between the signal input and a storage capacitor. The gates are controlled by a high speed row clock and low speed column clock so that the instantaneous analog value of the signal is only sampled and stored by each cell on coincidence of the two clocks. 6 figs.

  14. IC and Component Selection for Space Systems

    NASA Technical Reports Server (NTRS)

    Label, Kenneth A.; Cohn, Lewis M.

    2007-01-01

    This viewgraph presentation reviews the integrated circuit (IC) and selections of the IC components for space systems. Included in the discussion are a overview of semiconductors and the evolution of integrated circuit. It also reviews the three different viewpoints of the IC selection: technical, programmatic, and risk. From a radiation perspective there are four criteria for selecting ICs for space systems: guaranteed hardness, historical ground-based data, historical flight usage, and unknown assurance.

  15. Rocket Observations of IC 405

    NASA Astrophysics Data System (ADS)

    France, K.; McCandliss, S. R.; Feldman, P. D.; Burgh, E. B.

    2001-12-01

    We present the preliminary results from a NASA/JHU sounding rocket mission (36.198 UG), launched on 09 February 2001 at 21:00 MST, to obtain a long slit (200\\arcsec x 12\\arcsec) spectrum of the reflection nebula IC 405 in the 900 -- 1400 Å wavelength region. Several pointings within the nebula were obtained, including a high quality (S/N ≈ 10-15 at R = 300) spectrum of the central star, HD 34078, which clearly shows absorption from molecular hydrogen (H2). Observations of the nebula reveal a surface brightness to stellar flux ratio that rises by two orders of magnitude between 1400 and 900 Å. This is in contrast with the relatively flat nebular dust scattering observed during a prior sounding rocket observation of the reflection nebula NGC 2023. We will also present additional nebular pointings within IC 405, including a region observed by the Hopkins Ultraviolet Telescope showing evidence of H2 fluorescent emission. These observations were supported by NASA grant NAG5-5122 to the Johns Hopkins University.

  16. Design and synthesis of tetraol derivatives of 1,12-dicarba-closo-dodecaborane as non-secosteroidal vitamin D analogs.

    PubMed

    Fujii, Shinya; Kano, Atsushi; Masuno, Hiroyuki; Songkram, Chalermkiat; Kawachi, Emiko; Hirano, Tomoya; Tanatani, Aya; Kagechika, Hiroyuki

    2014-09-15

    Vitamin D receptor (VDR), a nuclear receptor for 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3, 1), is a promising target for multiple clinical applications. We recently developed non-secosteroidal VDR ligands based on a carbon-containing boron cluster, 1,12-dicarba-closo-dodecaborane (p-carborane), and examined the binding of one of them to VDR by means of crystallographic analysis. Here, we utilized that X-ray structure to design novel p-carborane-based tetraol-type vitamin D analogs, and we examined the biological activities of the synthesized compounds. Structure-activity relationship study revealed that introduction of an ω-hydroxyalkoxy functionality enhanced the biological activity, and the configuration of the substituent significantly influenced the potency. Among the synthesized compounds, 4-hydroxybutoxy derivative 9a exhibited the most potent activity, which was equal to that of the secosteroidal vitamin D analog, 19-nor-1α,25-dihydroxyvitamin D3 (2). Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Design and evaluation of wide-range and low-power analog front-end enabling body-implanted devices to monitor charge injection properties

    NASA Astrophysics Data System (ADS)

    Ito, Keita; Uno, Shoma; Goto, Tatsuya; Takezawa, Yoshiki; Harashima, Takuya; Morikawa, Takumi; Nishino, Satoru; Kino, Hisashi; Kiyoyama, Koji; Tanaka, Tetsu

    2017-04-01

    For safe electrical stimulation with body-implanted devices, the degradation of stimulus electrodes must be considered because it causes the unexpected electrolysis of water and the destruction of tissues. To monitor the charge injection property (CIP) of stimulus electrodes while these devices are implanted, we have proposed a charge injection monitoring system (CIMS). CIMS can safely read out voltages produced by a biphasic current pulse to a stimulus electrode and CIP is calculated from waveforms of the acquired voltages. In this paper, we describe a wide-range and low-power analog front-end (AFE) for CIMS that has variable gain-frequency characteristics and low-power analog-to-digital (A/D) conversion to adjust to the degradation of stimulus electrodes. The designed AFE was fabricated with 0.18 µm CMOS technology and achieved a valuable gain of 20-60 dB, an upper cutoff frequency of 0.2-10 kHz, and low-power interleaving A/D conversion. In addition, we successfully measured the CIP of stimulus electrodes for body-implanted devices using CIMS.

  18. Do Cross-circle Designs, the Mayan World Tree, Chitto Tustenuggee's, and Miami's Tequesta, Sites have Analogs in Brazil as they have in Peru, Europe, and Africa?

    NASA Astrophysics Data System (ADS)

    Ataide, Jade; Mc Leod, Roger; Mc Leod, David

    2007-04-01

    Florida's Miami Tequesta site conveys information about potential tornadoes, hurricanes, and even earthquakes. It is visually analogous to cross-circle designs, like other equivalent sites we have located, as in Maine, New Hampshire, in Medicine Wheels, and elsewhere. We focus on the detectable effects of time-and-place dependent electromagnetic signals. Non-technologic societies, and individuals, still find and use them, even today, especially in places like Cuzco, Peru. Modes of detection involve senses, such as sensitive, observant eyesight, and electromagnetically induced nerve signals interpreted as tinnitus, as traditionally indicated by ``Kokopelli's'' flute-playing, ``pins and needles,'' or even odor sensations. Recorded events show that youthful children are sometimes involved, as by Pacal's Classic-Mayan-era son, who became Kan Balum, Serpent Jaguar. Our intent is to check whether similar signals can be technologically identified in Brazil and New England. Site information investigated by us seems to be driven by the electromagnetic field. Enigmatic Brazilian locations should be technologically investigated with site correlations to other possible analogs, such as Florida's Chitto Tustenuggee site at Miramar. To cite this abstract, use the following reference: http://meetings.aps.org/link/BAPS.2007.NES07.C2.6

  19. The design of CMOS general-purpose analog front-end circuit with tunable gain and bandwidth for biopotential signal recording systems.

    PubMed

    Chen, Wei-Ming; Yang, Wen-Chia; Tsai, Tzung-Yun; Chiueh, Herming; Wu, Chung-Yu

    2011-01-01

    In this paper an 8-channel CMOS general-purpose analog front-end (AFE) circuit with tunable gain and bandwidth for biopotential signal recording systems is presented. The proposed AFE consists of eight chopper stabilized pre-amplifiers, an 8-to-1 analog multiplexer, and a programmable gain amplifier. It can be used to sense and amplify different kinds of biopotential signals, such as electrocorticogram (ECoG), electrocardiogram (ECG) and electromyogram (EMG). The AFE chip is designed and fabricated in 0.18-μm CMOS technology. The measured maximum gain of AFE is 60.8 dB. The low cutoff frequency can achieve as low as 0.8 Hz and high cutoff frequency can be adjusted from 200 Hz to 10 kHz to suit for different kinds of biopotential signals. The measured input-referred noise is 0.9 μV(rms), with the power consumption of 18μW per channel at 1.8-V power supply. And the noise efficiency factor (NEF) is only 1.3 for pre-amplifier.

  20. Design and pharmacological activity of glycinamide and N-methoxy amide derivatives of analogs and constitutional isomers of valproic acid.

    PubMed

    Pessah, Neta; Yagen, Boris; Hen, Naama; Shimshoni, Jakob A; Wlodarczyk, Bogdan; Finnell, Richard H; Bialer, Meir

    2011-11-01

    A series of glycinamide conjugates and N-methoxy amide derivatives of valproic acid (VPA) analogs and constitutional isomers were synthesized and evaluated for anticonvulsant activity. Of all compounds synthesized and tested, only N-methoxy-valnoctamide (N-methoxy-VCD) possessed better activity than VPA in the following anticonvulsant tests: maximal electroshock, subcutaneous metrazol, and 6-Hz (32-mA) seizure tests. In mice, the ED(50) values of N-methoxy-VCD were 142 mg/kg (maximal electroshock test), 70 mg/kg (subcutaneous metrazol test), and 35 mg/kg (6-Hz test), and its neurotoxicity TD(50) was 118 mg/kg. In rats, the ED(50) of N-methoxy-VCD in the subcutaneous metrazol test was 36 mg/kg and its protective index (PI=TD(50)/ED(50)) was >5.5. In the rat pilocarpine-induced status epilepticus model, N-methoxy-VCD demonstrated full protection at 200mg/kg, without any neurotoxicity. N-Methoxy-VCD was tested for its ability to induce teratogenicity in a mouse strain susceptible to VPA-induced teratogenicity and was found to be nonteratogenic, although it caused some resorptions. Nevertheless, a safety margin was still maintained between the ED(50) values of N-methoxy-VCD in the mouse subcutaneous metrazol test and the doses that caused the resorptions. On the basis of these results, N-methoxy-VCD is a good candidate for further evaluation as a new anticonvulsant and central nervous system drug. Copyright © 2011. Published by Elsevier Inc.

  1. SPIROC: design and performances of a dedicated very front-end electronics for an ILC Analog Hadronic CALorimeter (AHCAL) prototype with SiPM read-out

    NASA Astrophysics Data System (ADS)

    Conforti Di Lorenzo, S.; Callier, S.; Fleury, J.; Dulucq, F.; De la Taille, C.; Chassard, G. Martin; Raux, L.; Seguin-Moreau, N.

    2013-01-01

    For the future e+ e- International Linear Collider (ILC) the ASIC SPIROC (Silicon Photomultiplier Integrated Read-Out Chip) was designed to read out the Analog Hadronic Calorimeter (AHCAL) equipped with Silicon Photomultiplier (SiPM). It is an evolution of the FLC_SiPM chip designed by the OMEGA group in 2005. SPIROC2 [1] was realized in AMS SiGe 0.35 μm technology [2] and developed to match the requirements of large dynamic range, low noise, low consumption, high precision and large number of read-out channels. This ASIC is a very front-end read-out chip that integrates 36 self triggered channels with variable gain to achieve charge and time measurements. The charge measurement must be performed from 1 up to 2000 photo-electrons (p.e.) corresponding to 160 fC up to 320 pC for SiPM gain 106. The time measurement is performed with a coarse 12-bit counter related to the bunch crossing clock (up to 5 MHz) and a fine time ramp based on this clock (down to 200 ns) to achieve a resolution of 1 ns. An analog memory array with a depth of 16 for each channel is used to store the time information and the charge measurement. The analog memory content (time and charge) is digitized thanks to an internal 12-bit Wilkinson ADC. The data is then stored in a 4kbytes RAM. A complex digital part is necessary to manage all these features and to transfer the data to the DAQ. SPIROC2 is the second generation of the SPIROC ASIC family designed in 2008 by the OMEGA group. A very similar version (SPIROC2c) was submitted in February 2012 to improve the noise performance and also to integrate a new TDC (Time to Digital Converter) structure. This paper describes SPIROC2 and SPIROC2c ASICs and illustrates the main characteristics thank to a series of measurements.

  2. 100 gigasamples per second 12 bits optoelectronic analog-to-digital converter design and implementation based on cellular polyphase-sampling architecture

    NASA Astrophysics Data System (ADS)

    Villa-Angulo, Carlos

    The next generation digital information systems such as high performance computers, multigigabit/sec communication networks, distributed sensors, three dimensional digital imaging systems etc, will require analog-to-digital converters (ADCs) with high sampling rates exceeding 10 Gigasamples per second (GSPS) and high bit resolution of at least 10 bits. Such performance criteria are difficult to achieve with silicon electronics technology because the switching speeds peak at about 10-20GHz. Also, timing jitters, amplitude fluctuations, phase noise, thermal noise, and harmonic distortion, all contribute to reductions in ADC bit resolution as sampling rate increases. Photonics ADCs are rapidly emerging as the enabling technologies for high-performance digital signal processing systems. For this technology, high optical pulses repetition rate (in the order of GHz) with low time jitter and pulse width in the femtoseconds regime are the major attractive characteristics of optical sources. In this dissertation work, a novel 102.4 GSPS 12-bit optoelectronic analog-to-digital converter architecture that is based on a Cellular Polyphase-Sampling architecture is introduced. First, a 102.4 GHz all-optical clock was designed and implemented using a femtosecond laser source and passive optical components. Second, a novel optoelectronic architecture for optical sampling and parallel demultiplexing of different phases (polyphase) of an input analog signal is presented. The optoelectronic sampling and demultiplexing architecture is composed by 20 optoelectronic subcircuit referred as "OE-Cell"; these have been designed and implemented using optical passive components and InGaAs PIN photodiodes. A unique feature of this approach is that the optically sampled RF signal always remains in the electrical domain and thus eliminates the need for electrical-to-optical and optical-to-electrical conversions. The electrical-in to electrical-out transfer functions of the sampling and

  3. Utilizing CMP-Sialic Acid Analogs to Unravel Neisseria gonorrhoeae Lipooligosaccharide-Mediated Complement Resistance and Design Novel Therapeutics.

    PubMed

    Gulati, Sunita; Schoenhofen, Ian C; Whitfield, Dennis M; Cox, Andrew D; Li, Jianjun; St Michael, Frank; Vinogradov, Evgeny V; Stupak, Jacek; Zheng, Bo; Ohnishi, Makoto; Unemo, Magnus; Lewis, Lisa A; Taylor, Rachel E; Landig, Corinna S; Diaz, Sandra; Reed, George W; Varki, Ajit; Rice, Peter A; Ram, Sanjay

    2015-12-01

    -Leg5Ac7Ac-treated mice were sensitive to human complement ex vivo, simulating in vitro findings. These data reveal critical roles for the Sia exocyclic side-chain in gonococcal serum-resistance. Such CMP-NulO analogs may provide a novel therapeutic strategy against the global threat of multidrug-resistant gonorrhea.

  4. Utilizing CMP-Sialic Acid Analogs to Unravel Neisseria gonorrhoeae Lipooligosaccharide-Mediated Complement Resistance and Design Novel Therapeutics

    PubMed Central

    Gulati, Sunita; Schoenhofen, Ian C.; Whitfield, Dennis M.; Cox, Andrew D.; Li, Jianjun; St. Michael, Frank; Vinogradov, Evgeny V.; Stupak, Jacek; Zheng, Bo; Ohnishi, Makoto; Unemo, Magnus; Lewis, Lisa A.; Taylor, Rachel E.; Landig, Corinna S.; Diaz, Sandra; Reed, George W.; Varki, Ajit; Rice, Peter A.; Ram, Sanjay

    2015-01-01

    CMP-Leg5Ac7Ac-treated mice were sensitive to human complement ex vivo, simulating in vitro findings. These data reveal critical roles for the Sia exocyclic side-chain in gonococcal serum-resistance. Such CMP-NulO analogs may provide a novel therapeutic strategy against the global threat of multidrug-resistant gonorrhea. PMID:26630657

  5. A 2.5 mW/ch, 50 Mcps, 10-Analog Channel, Adaptively Biased Read-Out Front-End IC With Low Intrinsic Timing Resolution for Single-Photon Time-of-Flight PET Applications With Time-Dependent Noise Analysis in 90 nm CMOS.

    PubMed

    Cruz, Hugo; Huang, Hong-Yi; Luo, Ching-Hsing; Lee, Shuenn-Yuh

    2017-04-01

    This paper presents a 10-channel time-of-flight application-specific integrated circuit (ASIC) for positron emission tomography in a 90 nm standard CMOS process. To overcome variations in channel-to-channel timing resolution caused by mismatch and process variations, adaptive biases and a digital-to-analog converter (DAC) are utilized. The main contributions of this work are as follows. First, multistage architectures reduce the total power consumption, and detection bandwidths of analog preamplifiers and comparators are increased to 1 and 1.5 GHz, respectively, relative to those in previous studies. Second, a total intrinsic electronic timing resolution of 9.71 ps root-mean-square (RMS) is achieved (13.88 ps peak and 11.8 ps average of the 10 channels in 5 ASICs). Third, the proposed architecture reduces variations in channel-to-channel timing resolution to 2.6 bits (equivalent to 4.17 ps RMS) by calibrating analog comparator threshold levels. A 181.5 ps full-width-at-half-maximum timing resolution is measured with an avalanche photo diode and a laser setup. The power consumption is 2.5 mW using 0.5 and 1.2 V power supplies. The proposed ASIC is implemented in a 90 nm TSMC CMOS process with a total area of 3.3 mm × 2.7 mm.

  6. Thackeray's Globules in IC 2944

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Strangely glowing dark clouds float serenely in this remarkable and beautiful image taken with NASA's Hubble Space Telescope. These dense, opaque dust clouds - known as 'globules' - are silhouetted against nearby bright stars in the busy star-forming region, IC 2944. These globules were first found in IC 2944 by astronomer A.D. Thackeray in 1950. Although globules like these have been known since Dutch-American astronomer Bart Bok first drew attention to such objects in 1947, little is still known about their origin and nature, except that they are generally associated with areas of star formation, called 'HII regions' due to the presence of hydrogen gas. The largest of the globules in this image is actually two separate clouds that gently overlap along our line of sight. Each cloud is nearly 1.4 light-years (50 arcseconds) along its longest dimension, and collectively, they contain enough material to equal over 15 solar masses. IC 2944, the surrounding HII region, is filled with gas and dust that is illuminated and heated by a loose cluster of O-type stars. These stars are much hotter and much more massive than our Sun. IC 2944 is relatively close by, located only 5900 light-years (1800 parsecs) away in the constellation Centaurus. Thanks to the remarkable resolution offered by the Hubble Space Telescope, astronomers can for the first time study the intricate structure of these globules. The globules appear to be heavily fractured, as if major forces were tearing them apart. When radio astronomers observed the faint hiss of molecules within the globules, they realized that the globules are actually in constant, churning motion, moving supersonically among each other. This may be caused by the powerful ultraviolet radiation from the luminous, massive stars, which also heat up the gas in the HII region, causing it to expand and stream against the globules, leading to their destruction. Despite their serene appearance, the globules may actually be likened to clumps

  7. Thackeray's Globules in IC 2944

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Strangely glowing dark clouds float serenely in this remarkable and beautiful image taken with NASA's Hubble Space Telescope. These dense, opaque dust clouds - known as 'globules' - are silhouetted against nearby bright stars in the busy star-forming region, IC 2944. These globules were first found in IC 2944 by astronomer A.D. Thackeray in 1950. Although globules like these have been known since Dutch-American astronomer Bart Bok first drew attention to such objects in 1947, little is still known about their origin and nature, except that they are generally associated with areas of star formation, called 'HII regions' due to the presence of hydrogen gas. The largest of the globules in this image is actually two separate clouds that gently overlap along our line of sight. Each cloud is nearly 1.4 light-years (50 arcseconds) along its longest dimension, and collectively, they contain enough material to equal over 15 solar masses. IC 2944, the surrounding HII region, is filled with gas and dust that is illuminated and heated by a loose cluster of O-type stars. These stars are much hotter and much more massive than our Sun. IC 2944 is relatively close by, located only 5900 light-years (1800 parsecs) away in the constellation Centaurus. Thanks to the remarkable resolution offered by the Hubble Space Telescope, astronomers can for the first time study the intricate structure of these globules. The globules appear to be heavily fractured, as if major forces were tearing them apart. When radio astronomers observed the faint hiss of molecules within the globules, they realized that the globules are actually in constant, churning motion, moving supersonically among each other. This may be caused by the powerful ultraviolet radiation from the luminous, massive stars, which also heat up the gas in the HII region, causing it to expand and stream against the globules, leading to their destruction. Despite their serene appearance, the globules may actually be likened to clumps

  8. SPITZER OBSERVATIONS OF IC 2118

    SciTech Connect

    Guieu, S.; Rebull, L. M.; Stauffer, J. R.; Noriega-Crespo, A.; Cole, D. M.; Flagey, N.; Laher, R.; Stolovy, S.; Spuck, T.; Roelofsen Moody, T.; Sepulveda, B.; Weehler, C.; Maranto, A.; Penprase, B.; Ramirez, S.

    2010-09-01

    IC 2118, also known as the Witch Head Nebula, is a wispy, roughly cometary, {approx}5 degree long reflection nebula, and is thought to be a site of triggered star formation. In order to search for new young stellar objects (YSOs), we have observed this region in seven mid- and far-infrared bands using the Spitzer Space Telescope and in four bands in the optical using the U. S. Naval Observatory 40 inch telescope. We find infrared excesses in four of the six previously known T Tauri stars in our combined infrared maps, and we find six entirely new candidate YSOs, one of which may be an edge-on disk. Most of the YSOs seen in the infrared are Class II objects, and they are all in the 'head' of the nebula, within the most massive molecular cloud of the region.

  9. Design, synthesis and anti flaviviridae activity of N(6)-, 5',3'-O- and 5',2'-O-substituted adenine nucleoside analogs.

    PubMed

    Angusti, Angela; Manfredini, Stefano; Durini, Elisa; Ciliberti, Nunzia; Vertuani, Silvia; Solaroli, Nicola; Pricl, Sabrina; Ferrone, Marco; Fermeglia, Maurizio; Loddo, Roberta; Secci, Barbara; Visioli, Anna; Sanna, Tiziana; Collu, Gabriella; Pezzullo, Margherita; La Colla, Paolo

    2008-04-01

    During a random screening of representative libraries of nucleoside analogues we discovered that the adenine derivatives FEVB28 and FEG118 were Flaviviridae inhibitors endowed with potency comparable, if not superior, to that of ribavirin. Those studies prompted us to design a new class of protected nucleoside analogs, reported herein, which displays interesting anti-bovine viral diarrhea virus (BVDV) activity and low cytotoxicity in cell-based assays (4, 23, 29 EC(50): 14, 11, 26 microM respectively, CC(50)>100 microM) and appreciable activity in enzyme assays against the RNA dependent RNA polymerase (RdRp) of BVDV (4, 23, 29, RdRp inhibition activity 27, 16, 15 microM respectively). A molecular modeling study was also carried out to highlight the possible interactions between this compounds class and the corresponding hepatitis C virus (HCV) enzyme.

  10. Star Formation in IC 348

    NASA Astrophysics Data System (ADS)

    Herbst, W.

    2008-12-01

    A review of work on the small, compact, nearby young cluster IC 348 is given. This region is particularly important because it is well surveyed at a variety of wavelengths and intermediate in nature between dense clusters and loose associations. Its earliest type star is B5 and it contains a few hundred stellar members as well as some brown dwarfs, protostars, Herbig-Haro objects and starless sub-mm cores. The total mass of its components is ˜90 M_⊙, most of which is in the form of pre-main sequence stars. Perhaps the biggest challenge to work on the cluster is the relatively high and variable extinction (A_v=3D1-7 mag). Studies to date have provided particularly valuable insights into the initial mass function, disk lifetimes, stellar rotation properties, X-ray properties, outflows and substructure of the cluster. Results on the stellar component include the following: 1) the initial mass function matches that for field stars in the stellar and brown dwarf regimes, 2) the fraction of stars with disks is probably normal for the cluster's age, 3) the rotation properties match those of the Orion Nebula Cluster and are significantly different, in the sense of slower rotation, than NGC 2264, 4) the X-ray properties of the stars appear normal for T Tauri stars. There is a ridge of high extinction that lies ˜10 arcmin (0.9 pc in projection) to the southwest of IC 348 and contains about a dozen Class 0 and I protostars as well as some Herbig Haro objects and sub-mm cores. This region, which also contains the "Flying Ghost Nebula" and the well-studied object HH 211, clearly signals that star formation in this part of the Perseus dark clouds is not yet finished. An extensive kinematical study involving both proper motions and radial velocities for the 400 members of the cluster would be most desirable.

  11. Computational Protein Design to Re-Engineer Stromal Cell-Derived Factor-1α (SDF) Generates an Effective and Translatable Angiogenic Polypeptide Analog

    PubMed Central

    Hiesinger, William; Perez-Aguilar, Jose Manuel; Atluri, Pavan; Marotta, Nicole A.; Frederick, John R.; Fitzpatrick, J. Raymond; McCormick, Ryan C.; Muenzer, Jeffrey R.; Yang, Elaine C.; Levit, Rebecca D.; Yuan, Li-Jun; MacArthur, John W.; Saven, Jeffery G.; Woo, Y. Joseph

    2014-01-01

    BACKGROUND After ischemic injury, cardiac secretion of the potent endothelial progenitor stem cell (EPC) chemokine SDF stimulates endogenous neovascularization and myocardial repair, a process insufficiently robust to repair major infarcts. Experimentally, exogenous administration of recombinant SDF enhances neovasculogenesis and cardiac function after MI. However, SDF has a short half-life, is bulky, and very expensive. Smaller analogs of SDF may provide translational advantages including enhanced stability and function, ease of synthesis, lower cost, and potential modulated delivery via engineered biomaterials. In this study, computational protein design was used to create a more efficient evolution of the native SDF protein. METHODS and RESULTS Protein structure model was used to engineer an SDF polypeptide analog (ESA) that splices the N-terminus (activation and binding) and C-terminus (extracellular stabilization) with a diproline segment designed to limit the conformational flexibility of the peptide backbone and retain the relative orientation of these segments observed in the native structure of SDF. EPCs in ESA gradient, assayed by Boyden chamber, showed significantly increased migration compared to both SDF and control gradients (ESA 567±74 cells/HPF vs SDF 438±46 p=0.037; vs Control 156±45 p=0.001). EPC receptor activation was evaluated by quantifying phosphorylated AKT. ESA had significantly greater pAKT levels than SDF and control (1.64±0.24 vs 1.26±0.187, p=0.01; vs. 0.95±0.08, p<0.001). Angiogenic growth factor assays revealed a distinct increase in Angiopoietin-1 expression in the ESA and SDF treated hearts. Also, CD-1 mice (n=30) underwent LAD ligation and peri-infarct intramyocardial injection of ESA, SDF-1α, or saline. At 2 weeks, echocardiography demonstrated a significant gain in EF, CO, SV, and Fractional Area Change (FAC) in mice treated with ESA when compared to controls and significant improvement in FAC when compared to SDF treated

  12. A bipolar analog front-end integrated circuit for the SDC silicon tracker

    SciTech Connect

    Kipnis, I.; Spieler, H.; Collins, T.

    1993-11-01

    A low-noise, low-power, high-bandwidth, radiation hard, silicon bipolar-transistor full-custom integrated circuit (IC) containing 64 channels of analog signal processing has been developed for the SDC silicon tracker. The IC was designed and tested at LBL and was fabricated using AT&T`s CBIC-U2, 4 GHz f{sub T} complementary bipolar technology. Each channel contains the following functions: low-noise preamplification, pulse shaping and threshold discrimination. This is the first iteration of the production analog IC for the SDC silicon tracker. The IC is laid out to directly match the 50 {mu}m pitch double-sided silicon strip detector. The chip measures 6.8 mm {times} 3.1 mm and contains 3,600 transistors. Three stages of amplification provide 180 mV/fC of gain with a 35 nsec peaking time at the comparator input. For a 14 pF detector capacitance, the equivalent noise charge is 1300 el. rms at a power consumption of 1 mW/channel from a single 3.5 V supply. With the discriminator threshold set to 4 times the noise level, a 16 nsec time-walk for 1.25 to 10fC signals is achieved using a time-walk compensation network. Irradiation tests at TRIUMF to a {Phi}=10{sup 14} protons/cm{sup 2} have been performed on the IC, demonstrating the radiation hardness of the complementary bipolar process.

  13. Characterization of an Electro-Absorption Modulator Design With High-Dynamic Range for Broadband Analog Applications

    DTIC Science & Technology

    2008-03-01

    electroabsorption modulator monolithically integrated with a DFB laser,” Optical Technology for Microwave Applications VII, Proc. SPIE, Vol. 2560, pp. 19...extremely compact and integrated package to be fabricated with single mode fiber pigtails. The transfer function’s shape permits suppression of higher...Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 Characterization of an electroabsorption modulator design with high- dynamic range for

  14. Mod 1 ICS TI Report: ICS Conversion of a 140% HPGe Detector

    SciTech Connect

    Bounds, John Alan

    2016-07-05

    This report evaluates the Mod 1 ICS, an electrically cooled 140% HPGe detector. It is a custom version of the ORTEC Integrated Cooling System (ICS) modified to make it more practical for us to use in the field. Performance and operating characteristics of the Mod 1 ICS are documented, noting both pros and cons. The Mod 1 ICS is deemed a success. Recommendations for a Mod 2 ICS, a true field prototype, are provided.

  15. BusWorld: an analog pilot test of a virtual environment designed to treat posttraumatic stress disorder originating from a terrorist suicide bomb attack.

    PubMed

    Josman, Naomi; Reisberg, Ayelet; Weiss, Patrice L; Garcia-Palacios, Azucena; Hoffman, Hunter G

    2008-12-01

    Exposure therapy treatment can lead to large reductions in posttraumatic stress disorder (PTSD) symptoms. Virtual reality exposure (VRE) therapy is designed to facilitate cognitive behavioral therapy for PTSD. During VRE therapy, patients go into an immersive computer-generated environment (go back to the scene of the traumatic event) to help them gain access to their memories of the traumatic event, change unhealthy thought patterns, gradually habituate to their anxiety, and reduce the intensity of associated emotions. The therapist's ability to manipulate the amount of anxiety experienced by the client during therapy is an important element of successful exposure therapy. Using a within-subjects design, 30 asymptomatic volunteers each experienced four levels of a virtual world depicting a terrorist bus bombing, designed to be increasingly distressful. There was a statistically significant difference between the mean subjective units of discomfort scores (SUDS) of the four levels, and several planned paired comparisons showed significantly higher SUDS ratings with higher simulation levels. Results suggest that sound may play an important role in successful elicitation of emotional responses during VRE. The results of this analog study provide initial validation of the potential of BusWorld to provide graded exposure for individuals suffering from PTSD originating from suicide bus bombings. Future research exploring whether VR exposure therapy with BusWorld can reduce PTSD in clinical patients is warranted.

  16. Orthographic analogies and developmental dyslexia.

    PubMed

    Hanley, J R; Reynolds, C J; Thornton, A

    1997-08-01

    Goswami (1986, 1988) has demonstrated that children can use orthographic analogies (particularly at the onset-rime level) between the spelling patterns in words to help to decode new words (e.g. using 'beak' to read 'peak'). This strategy has been shown in children as young as six years old. Since it is known that children with developmental dyslexia find it particularly difficult to read words that they have not been specifically taught (Lovett, Warren-Chaplin, Ransby & Borden, 1990), the present study investigated whether dyslexic children might be unable to use analogies. Employing a design similar to that used by Goswami (1988), it was hypothesized that dyslexics would find it difficult to transfer spontaneously knowledge of a 'clue' word to decode new words that could be read by analogy with the clue word. The results of Expt 1 indicated that the dyslexic readers read significantly fewer of the analogous words than a reading age-matched comparison group of younger children. Furthermore, none of the nine dyslexic children read as many of the analogous words as the lowest scoring control child. In a second experiment, a design similar to that of Muter, Snowling & Taylor (1994) was used with a new and larger sample of dyslexic children. In this experiment, all the children were brought to criterion in reading the clue words before the analogous words were presented. Once again, the dyslexic children read significantly fewer words that were analogous with the clue words than did a reading age-matched comparison group. The number of analogous words that the dyslexic children read was significantly correlated with their performance on a test that is sensitive to the ability to detect rhyme. It is argued that a failure to make analogies may be one of the main causes of the reading impairment experienced by children with developmental dyslexia.

  17. Experimental evaluation of incorporating digital and analog integrated circuit die on a common substrate utilizing silicon-hybrid wafer-scale integration technology

    NASA Astrophysics Data System (ADS)

    Reamy, Philip C.

    1992-03-01

    The objective of this research effort was to investigate the implementation of analog circuits in a wafer scale integration system. A test circuit composed of analog and digital subsystems was designed and tested through simulation. IC die containing this test circuit were utilized in the WSI system fabrication. Preliminary investigations were conducted to evaluate the potential improvements to the IC die mounting procedure, a key step in fabricating functional WSI systems. These investigations demonstrated a procedure which produced repeatable results in achieving acceptable planarization of IC die and host substrate surfaces. These investigations also demonstrated the successful application of a barrier coating material to prevent adhesion between the IC die adhesive and the reference flat during the IC die mounting procedure. An evaluation of candidate polyimides to be used as the interlevel dielectric in the WSI systems was also performed. Test samples for each of the WSI configurations were fabricated and tested for electrical continuity. Additional electrical characterization measurements were conducted on two of the test samples.

  18. High-Affinity α-Conotoxin PnIA Analogs Designed on the Basis of the Protein Surface Topography Method

    PubMed Central

    Kasheverov, Igor E.; Chugunov, Anton O.; Kudryavtsev, Denis S.; Ivanov, Igor A.; Zhmak, Maxim N.; Shelukhina, Irina V.; Spirova, Ekaterina N.; Tabakmakher, Valentin M.; Zelepuga, Elena A.; Efremov, Roman G.; Tsetlin, Victor I.

    2016-01-01

    Despite some success for small molecules, elucidating structure–function relationships for biologically active peptides — the ligands for various targets in the organism — remains a great challenge and calls for the development of novel approaches. Some of us recently proposed the Protein Surface Topography (PST) approach, which benefits from a simplified representation of biomolecules’ surface as projection maps, which enables the exposure of the structure–function dependencies. Here, we use PST to uncover the “activity pattern” in α-conotoxins — neuroactive peptides that effectively target nicotinic acetylcholine receptors (nAChRs). PST was applied in order to design several variants of the α-conotoxin PnIA, which were synthesized and thoroughly studied. Among the best was PnIA[R9, L10], which exhibits nanomolar affinity for the α7 nAChR, selectivity and a slow wash-out from this target. Importantly, these mutations could hardly be delineated by “standard” structure-based drug design. The proposed combination of PST with a set of experiments proved very efficient for the rational construction of new bioactive molecules. PMID:27841338

  19. High-Affinity α-Conotoxin PnIA Analogs Designed on the Basis of the Protein Surface Topography Method.

    PubMed

    Kasheverov, Igor E; Chugunov, Anton O; Kudryavtsev, Denis S; Ivanov, Igor A; Zhmak, Maxim N; Shelukhina, Irina V; Spirova, Ekaterina N; Tabakmakher, Valentin M; Zelepuga, Elena A; Efremov, Roman G; Tsetlin, Victor I

    2016-11-14

    Despite some success for small molecules, elucidating structure-function relationships for biologically active peptides - the ligands for various targets in the organism - remains a great challenge and calls for the development of novel approaches. Some of us recently proposed the Protein Surface Topography (PST) approach, which benefits from a simplified representation of biomolecules' surface as projection maps, which enables the exposure of the structure-function dependencies. Here, we use PST to uncover the "activity pattern" in α-conotoxins - neuroactive peptides that effectively target nicotinic acetylcholine receptors (nAChRs). PST was applied in order to design several variants of the α-conotoxin PnIA, which were synthesized and thoroughly studied. Among the best was PnIA[R9, L10], which exhibits nanomolar affinity for the α7 nAChR, selectivity and a slow wash-out from this target. Importantly, these mutations could hardly be delineated by "standard" structure-based drug design. The proposed combination of PST with a set of experiments proved very efficient for the rational construction of new bioactive molecules.

  20. PDC IC WELD FAILURE EVALUATION AND RESOLUTION

    SciTech Connect

    Korinko, P.; Howard, S.; Maxwell, D.; Fiscus, J.

    2012-04-16

    for the actual can welding process, however, did not result in an improved weld geometry. Several possibilities for the lack of positive response exist, some of which are that (1) an insufficient number of test articles were welded under prototypic conditions, (2) the process was not optimized so that significant improvements were observable over the 'noise', and (3) the in-situ arc anneal closed the gap down too much so the can was unable to exhaust pressure ahead of the weld. Several operational and mechanical improvements were identified. The weld clamps were changed to a design consistent with those used in the legacy operations. A helium puff operation was eliminated; it is believed that this operation was the cause of the original weld defect. Also, timing of plug mast movement was found to correspond with weld irregularities. The timing of the movement was changed to occur during weld head travel between tacks. In the end a three sequential tack weld process followed by a pulse weld at the same current and travel speed as was used for the legacy processes was suggested for use during the IC qualification effort. Relative to legacy welds, the PDC IC weld demonstrates greater fluctuation in the region of the weld located between tack welds. However, canister weld response (canister to canister) is consistent and with the aid of the optical mapping system (for targeting the cut position) is considered adequate. DR measurements and METs show the PDC IC welds to have sufficient ligament length to ensure adequate canister pressure/impact capacity and to ensure adequate stub function. The PDC welding process has not been optimized as a result of this effort. Differences remain between the legacy BTC welds and the PDC IC weld, but these differences are not sufficient to prevent resumption of the current PDC IC qualification effort. During the PDC IC qualification effort, a total of 17 cans will be welded and a variety of tests/inspections will be performed. The

  1. Development of a new air-stable structure-simplified nafuredin-γ analog as a potent and selective nematode complex I inhibitor.

    PubMed

    Ohtawa, Masaki; Arima, Shiho; Shimizu, Risa; Hanatani, Naomi; Shimizu, Eri; Shiomi, Kazuro; Kita, Kiyoshi; Ōmura, Satoshi; Nagamitsu, Tohru

    2017-02-22

    Nafuredin-γ, obtained from natural nafuredin, has demonstrated a potent and selective inhibitory activity against nematode complex I. However, nafuredin-γ is unstable in air since its conjugated dienes are oxygen-labile. The instability in air was naturally solved by the synthesis of structure-simplified nafuredin-γ analogs without conjugated dienes. However, these modified analogs showed lower complex I inhibitory activities. Therefore, new air-stable structure-simplified nafuredin-γ analogs were designed and synthesized herein. Among all analogs synthesized, the one bearing a unique 1-azabicyclo[3.1.0]hexane scaffold showed the highest inhibitory activity (IC50=170 nM) while presenting high selectivity against nematode complex I.The Journal of Antibiotics advance online publication, 22 February 2017; doi:10.1038/ja.2017.16.

  2. AnalogExplorer2 – Stereochemistry sensitive graphical analysis of large analog series

    PubMed Central

    Hu, Ye; Zhang, Bijun; Vogt, Martin; Bajorath, Jürgen

    2015-01-01

    AnalogExplorer is a computational methodology for the extraction and organization of series of structural analogs from compound data sets and their graphical analysis. The method is suitable for the analysis of large analog series originating from lead optimization programs. Herein we report AnalogExplorer2 designed to explicitly take stereochemical information during graphical analysis into account and describe a freely available deposition of the original AnalogExplorer program, AnalogExplorer2, and exemplary compound sets to illustrate their use. PMID:26913194

  3. AnalogExplorer2 - Stereochemistry sensitive graphical analysis of large analog series.

    PubMed

    Hu, Ye; Zhang, Bijun; Vogt, Martin; Bajorath, Jürgen

    2015-01-01

    AnalogExplorer is a computational methodology for the extraction and organization of series of structural analogs from compound data sets and their graphical analysis. The method is suitable for the analysis of large analog series originating from lead optimization programs. Herein we report AnalogExplorer2 designed to explicitly take stereochemical information during graphical analysis into account and describe a freely available deposition of the original AnalogExplorer program, AnalogExplorer2, and exemplary compound sets to illustrate their use.

  4. Synthesis of indole analogs as potent β-glucuronidase inhibitors.

    PubMed

    Baharudin, Mohd Syukri; Taha, Muhammad; Imran, Syahrul; Ismail, Nor Hadiani; Rahim, Fazal; Javid, Muhammad Tariq; Khan, Khalid Mohammed; Ali, Muhammad

    2017-06-01

    Natural products are the main source of motivation to design and synthesize new molecules for drug development. Designing new molecules against β-glucuronidase inhibitory is utmost essential. In this study indole analogs (1-35) were synthesized, characterized using various spectroscopic techniques including (1)H NMR and EI-MS and evaluated for their β-glucuronidase inhibitory activity. Most compounds were identified as potent inhibitors for the enzyme with IC50 values ranging between 0.50 and 53.40μM, with reference to standard d-saccharic acid 1,4-lactone (IC50=48.4±1.25μM). Structure-activity relationship had been also established. The results obtained from docking studies for the most active compound 10 showed that hydrogen bond donor features as well as hydrogen bonding with (Oε1) of nucleophilic residue Glu540 is believed to be the most importance interaction in the inhibition activity. It was also observed that hydroxyl at fourth position of benzylidene ring acts as a hydrogen bond donor and interacts with hydroxyl (OH) on the side chain of catalysis residue Tyr508. The enzyme-ligand complexed were being stabilized through electrostatic π-anion interaction with acid-base catalyst Glu451 (3.96Å) and thus preventing Glu451 from functioning as proton donor residue. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Hardware-Algorithms Co-Design and Implementation of an Analog-to-Information Converter for Biosignals Based on Compressed Sensing.

    PubMed

    Pareschi, Fabio; Albertini, Pierluigi; Frattini, Giovanni; Mangia, Mauro; Rovatti, Riccardo; Setti, Gianluca

    2016-02-01

    We report the design and implementation of an Analog-to-Information Converter (AIC) based on Compressed Sensing (CS). The system is realized in a CMOS 180 nm technology and targets the acquisition of bio-signals with Nyquist frequency up to 100 kHz. To maximize performance and reduce hardware complexity, we co-design hardware together with acquisition and reconstruction algorithms. The resulting AIC outperforms previously proposed solutions mainly thanks to two key features. First, we adopt a novel method to deal with saturations in the computation of CS measurements. This allows no loss in performance even when 60% of measurements saturate. Second, the system is able to adapt itself to the energy distribution of the input by exploiting the so-called rakeness to maximize the amount of information contained in the measurements. With this approach, the 16 measurement channels integrated into a single device are expected to allow the acquisition and the correct reconstruction of most biomedical signals. As a case study, measurements on real electrocardiograms (ECGs) and electromyograms (EMGs) show signals that these can be reconstructed without any noticeable degradation with a compression rate, respectively, of 8 and 10.

  6. The impact of underreporting and overreporting on the validity of the Personality Inventory for DSM-5 (PID-5): A simulation analog design investigation.

    PubMed

    Dhillon, Sonya; Bagby, R Michael; Kushner, Shauna C; Burchett, Danielle

    2017-04-01

    The Personality Inventory for DSM-5 (PID-5) is a 220-item self-report instrument that assesses the alternative model of personality psychopathology in Section III (Emerging Measures and Models) of DSM-5. Despite its relatively recent introduction, the PID-5 has generated an impressive accumulation of studies examining its psychometric properties, and the instrument is also already widely and frequently used in research studies. Although the PID-5 is psychometrically sound overall, reviews of this instrument express concern that this scale does not possess validity scales to detect invalidating levels of response bias, such as underreporting and overreporting. McGee Ng et al. (2016), using a "known-groups" (partial) criterion design, demonstrated that both underreporting and overreporting grossly affect mean scores on PID-5 scales. In the current investigation, we replicate these findings using an analog simulation design. An important extension to this replication study was the finding that the construct validity of the PID-5 was also significantly compromised by response bias, with statistically significant attenuation noted in validity coefficients of the PID-5 domain scales with scales from other instruments measuring congruent constructs. This attenuation was found for underreporting and overreporting bias. We believe there is a need to develop validity scales to screen for data-distorting response bias in research contexts and in clinical assessments where response bias is likely or otherwise suspected. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  7. A high-performance analog-to-digital conversion subsystem suitable for the study of evoked potentials, with design considerations for the eclipse $140 (trademark) computer

    NASA Astrophysics Data System (ADS)

    Berger, M. D.

    1983-02-01

    In order to evaluate impact protection devices, an impact injury model for restrained humans in a crash environment must be developed. Disruption of the functioning of the central nervous system is an important consequence of impact injury involving the head and neck, and is an important consideration in the development of a useful impact-injury model. Ultimately, neurophysiological criteria are desired. Evoked potentials (EPs) are likely to provide appropriate neurophysiological information, but quantitative analysis of EP data presents considerable difficulty. Among the technical problems encountered is efficient digitization of large amounts of EP data presents considerable difficulty. Among the technical problems encountered is efficient digitization of large amounts of EP data. This report presents detailed specifications for a high-performance analog-to-digital conversion subsystem suitable for various aspects of such work. Procedures utilizing various aspects of the design presented have been have been found to be effective. In the future acquisition of A/D conversion hardware, the design presented here should be considered.

  8. Design challenges of EO polymer based leaky waveguide deflector for 40 Gs/s all-optical analog-to-digital converters

    NASA Astrophysics Data System (ADS)

    Hadjloum, Massinissa; El Gibari, Mohammed; Li, Hongwu; Daryoush, Afshin S.

    2016-08-01

    Design challenges and performance optimization of an all-optical analog-to-digital converter (AOADC) is presented here. The paper addresses both microwave and optical design of a leaky waveguide optical deflector using electro-optic (E-O) polymer. The optical deflector converts magnitude variation of the applied RF voltage into variation of deflection angle out of a leaky waveguide optical beam using the linear E-O effect (Pockels effect) as part of the E-O polymer based optical waveguide. This variation of deflection angle as result of the applied RF signal is then quantized using optical windows followed by an array of high-speed photodetectors. We optimized the leakage coefficient of the leaky waveguide and its physical length to achieve the best trade-off between bandwidth and the deflected optical beam resolution, by improving the phase velocity matching between lightwave and microwave on one hand and using pre-emphasis technique to compensate for the RF signal attenuation on the other hand. In addition, for ease of access from both optical and RF perspective, a via-hole less broad bandwidth transition is designed between coplanar pads and coupled microstrip (CPW-CMS) driving electrodes. With the best reported E-O coefficient of 350 pm/V, the designed E-O deflector should allow an AOADC operating over 44 giga-samples-per-seconds with an estimated effective resolution of 6.5 bits on RF signals with Nyquist bandwidth of 22 GHz. The overall DC power consumption of all components used in this AOADC is of order of 4 W and is dominated by power consumption in the power amplifier to generate a 20 V RF voltage in 50 Ohm system. A higher sampling rate can be achieved at similar bits of resolution by interleaving a number of this elementary AOADC at the expense of a higher power consumption.

  9. Validating IC early-failure simulation

    NASA Astrophysics Data System (ADS)

    Moosa, Mohamod S.; Poole, Kelvin F.; Grams, Michael L.

    1995-09-01

    Early failures are the dominant concern as integrated circuit technology matures into consistently producing systems of high reliability. These failures are attributed to the presence of randomly occurring defects in elementary objects (contacts, vias, metal runs, gate oxides, bonds etc.) that result in extrinsic rather than intrinsic (wearout-related) mortality. A model relating system failure to failure at the elementary objective level has been developed. Reliability is modeled as a function of circuit architecture, mask layout, material properties, life-test data, worst-case use-conditions and the processing environment. The effects of competing failure mechanisms and the presence of redundant sub-systems are accounted for. Hierarchy is exploited in the analysis, allowing large scale designs to be simulated. Experimental validation of the modeling of oxide leakage related failure, based on correlation between actual failures reported for a production integrated circuit and Monte Carlo simulations that incorporate wafer-level test results and process defect monitor data, is presented. The state of the art in IC reliability simulation is advanced in that a methodology that provides the capability to design-in reliability while accounting for early failures has been developed; applications include process qualification, design assessment and fabrication monitoring.

  10. Knowledge-based IC-CAD software reuse

    NASA Astrophysics Data System (ADS)

    Zhang, Yueqiu; Yang, Lin; Tong, Jiarong; Tang, Pushan

    1996-03-01

    This paper discussed a method of knowledge representations to automatically reuse software information, such as, algorithms, designs, documents, reports etc. in the domain of IC-CAD. An architecture of framework ICSDE was presented which consists of four main parts: packaging unit, prototyping unit, reusable library and data base management. Within this framework, time domain knowledge of reusable-software-information (RSI) was represented and abstracted into three concept levels. Based on this representation method, the RSI can be packaged into reusable-software-component in the reusable library, and the function was provided to help IC-CAD software tools or system developers producing their products with low time and low cost. So it is possible to provide the IC-CAD products good reliability and maintainability under this framework.

  11. A Unified Submodular Framework for Multimodal IC Trojan Detection

    NASA Astrophysics Data System (ADS)

    Koushanfar, Farinaz; Mirhoseini, Azalia; Alkabani, Yousra

    This paper presents a unified formal framework for integrated circuits (IC) Trojan detection that can simultaneously employ multiple noninvasive measurement types. Hardware Trojans refer to modifications, alterations, or insertions to the original IC for adversarial purposes. The new framework formally defines the IC Trojan detection for each measurement type as an optimization problem and discusses the complexity. A formulation of the problem that is applicable to a large class of Trojan detection problems and is submodular is devised. Based on the objective function properties, an efficient Trojan detection method with strong approximation and optimality guarantees is introduced. Signal processing methods for calibrating the impact of inter-chip and intra-chip correlations are presented. We propose a number of methods for combining the detections of the different measurement types. Experimental evaluations on benchmark designs reveal the low-overhead and effectiveness of the new Trojan detection framework and provides a comparison of different detection combining methods.

  12. Development of CINPA1 analogs as novel and potent inverse agonists of constitutive androstane receptor.

    PubMed

    Lin, Wenwei; Yang, Lei; Chai, Sergio C; Lu, Yan; Chen, Taosheng

    2016-01-27

    Constitutive androstane receptor (CAR, NR1I3) and pregnane X receptor (PXR, NR1I2) are master regulators of endobiotic and xenobiotic metabolism and disposition. Because CAR is constitutively active in certain cellular contexts, inhibiting CAR might reduce drug-induced hepatotoxicity and resensitize drug-resistant cancer cells to chemotherapeutic drugs. We recently reported a novel CAR inhibitor/inverse agonist CINPA1 (11). Here, we have obtained or designed 54 analogs of CINPA1 and used a time-resolved fluorescence resonance energy transfer (TR-FRET) assay to evaluate their CAR inhibition potency. Many of the 54 analogs showed CAR inverse agonistic activities higher than those of CINPA1, which has an IC50 value of 687 nM. Among them, 72 has an IC50 value of 11.7 nM, which is about 59-fold more potent than CINPA1 and over 10-fold more potent than clotrimazole (an IC50 value of 126.9 nM), the most potent CAR inverse agonist in a biochemical assay previously reported by others. Docking studies provide a molecular explanation of the structure-activity relationship (SAR) observed experimentally. To our knowledge, this effort is the first chemistry endeavor in designing and identifying potent CAR inverse agonists based on a novel chemical scaffold, leading to 72 as the most potent CAR inverse agonist so far. The 54 chemicals presented are novel and unique tools for characterizing CAR's function, and the SAR information gained from these 54 analogs could guide future efforts to develop improved CAR inverse agonists.

  13. When Gesture Becomes Analogy.

    PubMed

    Cooperrider, Kensy; Goldin-Meadow, Susan

    2017-07-01

    Analogy researchers do not often examine gesture, and gesture researchers do not often borrow ideas from the study of analogy. One borrowable idea from the world of analogy is the importance of distinguishing between attributes and relations. Gentner (, ) observed that some metaphors highlight attributes and others highlight relations, and called the latter analogies. Mirroring this logic, we observe that some metaphoric gestures represent attributes and others represent relations, and propose to call the latter analogical gestures. We provide examples of such analogical gestures and show how they relate to the categories of iconic and metaphoric gestures described previously. Analogical gestures represent different types of relations and different degrees of relational complexity, and sometimes cohere into larger analogical models. Treating analogical gestures as a distinct phenomenon prompts new questions and predictions, and illustrates one way that the study of gesture and the study of analogy can be mutually informative. Copyright © 2017 Cognitive Science Society, Inc.

  14. Analog current mode analog/digital converter

    NASA Technical Reports Server (NTRS)

    Hadidi, Khayrollah (Inventor)

    1996-01-01

    An improved subranging or comparator circuit is provided for an analog-to-digital converter. As a subranging circuit, the circuit produces a residual signal representing the difference between an analog input signal and an analog of a digital representation. This is achieved by subdividing the digital representation into two or more parts and subtracting from the analog input signal analogs of each of the individual digital portions. In another aspect of the present invention, the subranging circuit comprises two sets of differential input pairs in which the transconductance of one differential input pair is scaled relative to the transconductance of the other differential input pair. As a consequence, the same resistor string may be used for two different digital-to-analog converters of the subranging circuit.

  15. A CMOS VLSI IC for real-time opto-electronic two-dimensional histogram generation

    NASA Astrophysics Data System (ADS)

    Richstein, James K.

    1993-12-01

    Histogram generation, a standard image processing operation, is a record of the intensity distribution in the image. Histogram generation has straightforward implementations on digital computers using high level languages. A prototype of an optical-electronic histogram generator was designed and tested for 1-D objects using wirewrapped MSI TTL components. The system has shown to be fairly modular in design. The aspects of the extension to two dimensions and the VLSI implementation of this design are discussed. In this paper, we report a VLSI design to be used in a two-dimensional real-time histogram generation scheme. The overall system design is such that the electronic signal obtained from the optically scanned two-dimensional semi-opaque image is processed and displayed within a period of one cycle of the scanning process. Specifically, in the VLSI implementation of the two-dimensional histogram generator, modifications were made to the original design. For the two-dimensional application, the output controller was analyzed as a finite state machine. The process used to describe the required timing signals and translate them to a VLSI finite state machine using Computer Aided Design Tools is discussed. In addition, the circuitry for sampling, binning, and display were combined with the timing circuitry on one IC. In the original design, the pulse width of the electronically sampled photodetector is limited with an analog one-shot. The high sampling rates associated with the extension to two dimensions requires significant reduction in the original 1-D prototype's sample pulse width of approximately 75 ns. The alternate design using VLSI logic gates will provide one-shot pulse widths of approximately 3 ns.

  16. 2-acetylphenol analogs as potent reversible monoamine oxidase inhibitors

    PubMed Central

    Legoabe, Lesetja J; Petzer, Anél; Petzer, Jacobus P

    2015-01-01

    Based on a previous report that substituted 2-acetylphenols may be promising leads for the design of novel monoamine oxidase (MAO) inhibitors, a series of C5-substituted 2-acetylphenol analogs (15) and related compounds (two) were synthesized and evaluated as inhibitors of human MAO-A and MAO-B. Generally, the study compounds exhibited inhibitory activities against both MAO-A and MAO-B, with selectivity for the B isoform. Among the compounds evaluated, seven compounds exhibited IC50 values <0.01 µM for MAO-B inhibition, with the most selective compound being 17,000-fold selective for MAO-B over the MAO-A isoform. Analyses of the structure–activity relationships for MAO inhibition show that substitution on the C5 position of the 2-acetylphenol moiety is a requirement for MAO-B inhibition, and the benzyloxy substituent is particularly favorable in this regard. This study concludes that C5-substituted 2-acetylphenol analogs are potent and selective MAO-B inhibitors, appropriate for the design of therapies for neurodegenerative disorders such as Parkinson’s disease. PMID:26203229

  17. Electromigration of damascene copper of IC interconnect

    NASA Astrophysics Data System (ADS)

    Meyer, William Kevin

    Copper metallization patterned with multi-level damascene process is prone to electromigration failure, which affects the reliability and performance of IC interconnect. In typical products, interconnect that is not already constrained by I·R drop or Joule self-heating operates at 'near threshold' conditions. Measurement of electromigration damage near threshold is very difficult due to slow degradation requiring greatly extended stress times, or high currents that cause thermal anomalies. Software simulations of the electromigration mechanism combined with characterization of temperature profiles allows extracting material parameters and calculation of design rules to ensure reliable interconnect. Test structures capable of demonstrating Blech threshold effects while allowing thermal characterization were designed and processed. Electromigration stress tests at various conditions were performed to extract both shortline (threshold) and long-line (above threshold) performance values. The resistance increase time constant shows immortality below Je·L (product of current density and segment length) of 3200 amp/cm. Statistical analysis of times-to-failure show that long lines last 105 hours at 3.1 mA/mum2 (120°C). While this is more robust than aluminum interconnect, the semiconductor industry will be challenged to improve that performance as future products require.

  18. An analog neural hardware implementation using charge-injection multipliers and neutron-specific gain control.

    PubMed

    Massengill, L W; Mundie, D B

    1992-01-01

    A neural network IC based on a dynamic charge injection is described. The hardware design is space and power efficient, and achieves massive parallelism of analog inner products via charge-based multipliers and spatially distributed summing buses. Basic synaptic cells are constructed of exponential pulse-decay modulation (EPDM) dynamic injection multipliers operating sequentially on propagating signal vectors and locally stored analog weights. Individually adjustable gain controls on each neutron reduce the effects of limited weight dynamic range. A hardware simulator/trainer has been developed which incorporates the physical (nonideal) characteristics of actual circuit components into the training process, thus absorbing nonlinearities and parametric deviations into the macroscopic performance of the network. Results show that charge-based techniques may achieve a high degree of neural density and throughput using standard CMOS processes.

  19. Analog front-end design of the STS/MUCH-XYTER2—full size prototype ASIC for the CBM experiment

    NASA Astrophysics Data System (ADS)

    Kleczek, Rafal

    2017-01-01

    The design of the analog front-end of the STS/MUCH-XYTER2 ASIC, a full-size prototype chip for the Silicon Tracking System (STS, based on double-sided silicon strip sensors) and Muon Chamber (MUCH, based on gas sensors) detectors is presented. The ASIC contains 128 charge processing channels, each built of a charge sensitive amplifier, a polarity selection circuit and two pulse shaping amplifiers forming two parallel signal paths. The first path is used for timing measurement with a fast discriminator. The second path allows low-noise amplitude measurement with a 5-bit continuous-time flash ADC. Different operating conditions and constraints posed by two target detectors' applications require front-end electronics flexibility to meet extended system-wise requirements. The presented circuit implements switchable shaper peaking time, gain switching and trimming, input amplifier pulsed reset circuit, fail-safe measures. The power consumption is scalable (for the STS and the MUCH modes), but limited to 10 mW/channel.

  20. Design, synthesis and molecular modeling of novel pyrido[2,3-d]pyrimidine analogs as antifolates: Application of Buchwald-Hartwig aminations of heterocycles

    PubMed Central

    Gangjee, Aleem; Namjoshi, Ojas A.; Raghavan, Sudhir; Queener, Sherry F.; Kisliuk, Roy L.; Cody, Vivian

    2013-01-01

    Opportunistic infections caused by Pneumocystis jirovecii (P. jirovecii, pj), Toxoplasma gondii (T. gondii, tg) and Mycobacterium avium (M. avium, ma) are the principal causes of morbidity and mortality in patients with acquired immunodeficiency syndrome (AIDS). The absence of any animal models for human Pneumocystis jirovecii pneumonia and the lack of crystal structures of pjDHFR and tgDHFR make the design of inhibitors challenging. A novel series of pyrido[2,3-d]pyrimidines as selective and potent DHFR inhibitors against these opportunistic infections are presented. Buchwald-Hartwig coupling reaction of substituted anilines with pivaloyl protected 2,4-diamino-6-bromo-pyrido[2,3-d]pyrimidine was successfully explored to synthesize these analogs. Compound 26 was the most selective inhibitor with excellent potency against pjDHFR. Molecular modeling studies with a pjDHFR homology model explained the potency and selectivity of 26. Structural data are also reported for 26 with pcDHFR and 16 and 22 with variants of pcDHFR. PMID:23627352

  1. The design of an analog module for sensor adaptation to changes in ambient light: a bio-inspired solution - biomed 2009.

    PubMed

    Dean, Brian; Wright, Cameron H G; Barrett, Steven F

    2009-01-01

    Fly inspired vision sensors have been shown to have many interesting qualities such as hyperacuity (or an ability to achieve movement resolution beyond the theoretical limit), extreme sensitivity to motion, and (through software simulation) image edge extraction, motion detection, and orientation and location of a line. Many of these qualities are beyond the ability of traditional computer vision sensors such as charge-coupled device (CCD) arrays. To obtain these characteristics, a prototype fly inspired sensor has been built and tested in a laboratory environment and shows promise. Any sophisticated visual system, whether man made or natural, must adequately adapt to lighting conditions, therefore light adaptation is a vital milestone in getting the afore mentioned prototype working in real-world conditions. By studying how the common house fly, Musca domestica, achieves this adaptation it was possible to design an analog solution to this problem. The solution utilizes instrumentation amplifiers and an additional sensor to sense the ambient light. This paper will examine this circuitry in greater detail and will explore the characterization and limitations of this solution.

  2. Design of a modified mouse protein with ligand binding properties of its human analog by molecular dynamics simulations: the case of C3 inhibition by compstatin.

    PubMed

    Tamamis, Phanourios; Pierou, Panayiota; Mytidou, Chrystalla; Floudas, Christodoulos A; Morikis, Dimitrios; Archontis, Georgios

    2011-11-01

    The peptide compstatin and its derivatives inhibit the complement-component protein C3 in primate mammals and are potential therapeutic agents against the unregulated activation of complement in humans, but are inactive against C3 from lower mammals. Recent molecular dynamics (MD) simulations showed that the most potent compstatin analog comprised entirely of natural amino acids (W4A9) had a smaller affinity for rat C3, due to reproducible changes in the rat protein structure with respect to the human protein, which eliminated or weakened specific protein-ligand interactions seen in the human C3:W4A9 complex. Here, we study by MD simulations three W4A9 complexes with the mouse C3 protein, and two "transgenic" mouse derivatives, containing a small number (6-9) of human C3 substitutions. The mouse complex experiences the conformational changes and affinity reduction of the rat complex. In the "transgenic" complexes, the conformation remains closer to that of the human complex, the protein-ligand interactions are improved, and the affinity for compstatin becomes "human-like." The present work creates new avenues for a compstatin-sensitive animal model. A similar strategy, involving the comparison of a series of complexes by MD simulations, could be used to design "transgenic" sequences in other systems. Copyright © 2011 Wiley-Liss, Inc.

  3. Design of a 10-bit segmented current-steering digital-to-analog converter in CMOS 65 nm technology for the bias of new generation readout chips in high radiation environment

    NASA Astrophysics Data System (ADS)

    De Robertis, G.; Loddo, F.; Mattiazzo, S.; Pacher, L.; Pantano, D.; Tamma, C.

    2016-01-01

    A new pixel front end chip for HL-LHC experiments in CMOS 65nm technology is under development by the CERN RD53 collaboration together with the Chipix65 INFN project. This work describes the design of a 10-bit segmented current-steering Digital-to-Analog Converter (DAC) to provide a programmable bias current to the analog blocks of the circuit. The main requirements are monotonicity, good linearity, limited area consumption and radiation hardness up to 10 MGy. The DAC was prototyped and electrically tested, while irradiation tests will be performed in Autumn 2015.

  4. The Front-End Readout as an Encoder IC for Magneto-Resistive Linear Scale Sensors

    PubMed Central

    Tran, Trong-Hieu; Chao, Paul Chang-Po; Chien, Ping-Chieh

    2016-01-01

    This study proposes a front-end readout circuit as an encoder chip for magneto-resistance (MR) linear scales. A typical MR sensor consists of two major parts: one is its base structure, also called the magnetic scale, which is embedded with multiple grid MR electrodes, while another is an “MR reader” stage with magnets inside and moving on the rails of the base. As the stage is in motion, the magnetic interaction between the moving stage and the base causes the variation of the magneto-resistances of the grid electrodes. In this study, a front-end readout IC chip is successfully designed and realized to acquire temporally-varying resistances in electrical signals as the stage is in motions. The acquired signals are in fact sinusoids and co-sinusoids, which are further deciphered by the front-end readout circuit via newly-designed programmable gain amplifiers (PGAs) and analog-to-digital converters (ADCs). The PGA is particularly designed to amplify the signals up to full dynamic ranges and up to 1 MHz. A 12-bit successive approximation register (SAR) ADC for analog-to-digital conversion is designed with linearity performance of ±1 in the least significant bit (LSB) over the input range of 0.5–2.5 V from peak to peak. The chip was fabricated by the Taiwan Semiconductor Manufacturing Company (TSMC) 0.35-micron complementary metal oxide semiconductor (CMOS) technology for verification with a chip size of 6.61 mm2, while the power consumption is 56 mW from a 5-V power supply. The measured integral non-linearity (INL) is −0.79–0.95 LSB while the differential non-linearity (DNL) is −0.68–0.72 LSB. The effective number of bits (ENOB) of the designed ADC is validated as 10.86 for converting the input analog signal to digital counterparts. Experimental validation was conducted. A digital decoder is orchestrated to decipher the harmonic outputs from the ADC via interpolation to the position of the moving stage. It was found that the displacement measurement

  5. The Front-End Readout as an Encoder IC for Magneto-Resistive Linear Scale Sensors.

    PubMed

    Tran, Trong-Hieu; Chao, Paul Chang-Po; Chien, Ping-Chieh

    2016-09-02

    This study proposes a front-end readout circuit as an encoder chip for magneto-resistance (MR) linear scales. A typical MR sensor consists of two major parts: one is its base structure, also called the magnetic scale, which is embedded with multiple grid MR electrodes, while another is an "MR reader" stage with magnets inside and moving on the rails of the base. As the stage is in motion, the magnetic interaction between the moving stage and the base causes the variation of the magneto-resistances of the grid electrodes. In this study, a front-end readout IC chip is successfully designed and realized to acquire temporally-varying resistances in electrical signals as the stage is in motions. The acquired signals are in fact sinusoids and co-sinusoids, which are further deciphered by the front-end readout circuit via newly-designed programmable gain amplifiers (PGAs) and analog-to-digital converters (ADCs). The PGA is particularly designed to amplify the signals up to full dynamic ranges and up to 1 MHz. A 12-bit successive approximation register (SAR) ADC for analog-to-digital conversion is designed with linearity performance of ±1 in the least significant bit (LSB) over the input range of 0.5-2.5 V from peak to peak. The chip was fabricated by the Taiwan Semiconductor Manufacturing Company (TSMC) 0.35-micron complementary metal oxide semiconductor (CMOS) technology for verification with a chip size of 6.61 mm², while the power consumption is 56 mW from a 5-V power supply. The measured integral non-linearity (INL) is -0.79-0.95 LSB while the differential non-linearity (DNL) is -0.68-0.72 LSB. The effective number of bits (ENOB) of the designed ADC is validated as 10.86 for converting the input analog signal to digital counterparts. Experimental validation was conducted. A digital decoder is orchestrated to decipher the harmonic outputs from the ADC via interpolation to the position of the moving stage. It was found that the displacement measurement error is within

  6. Systolic array IC for genetic computation

    NASA Astrophysics Data System (ADS)

    Anderson, D.

    Measuring similarities between large sequences of genetic information is a formidable task requiring enormous amounts of computer time. Geneticists claim that nearly two months of CRAY-2 time are required to run a single comparison of the known database against the new bases that will be found this year, and more than a CRAY-2 year for next year's genetic discoveries, and so on. The DNA IC, designed at HP-ICBD in cooperation with the California Institute of Technology and the Jet Propulsion Laboratory, is being implemented in order to move the task of genetic comparison onto workstations and personal computers, while vastly improving performance. The chip is a systolic (pumped) array comprised of 16 processors, control logic, and global RAM, totaling 400,000 FETS. At 12 MHz, each chip performs 2.7 billion 16 bit operations per second. Using 35 of these chips in series on one PC board (performing nearly 100 billion operations per second), a sequence of 560 bases can be compared against the eventual total genome of 3 billion bases, in minutes--on a personal computer. While the designed purpose of the DNA chip is for genetic research, other disciplines requiring similarity measurements between strings of 7 bit encoded data could make use of this chip as well. Cryptography and speech recognition are two examples. A mix of full custom design and standard cells, in CMOS34, were used to achieve these goals. Innovative test methods were developed to enhance controllability and observability in the array. This paper describes these techniques as well as the chip's functionality. This chip was designed in the 1989-90 timeframe.

  7. Systolic array IC for genetic computation

    NASA Technical Reports Server (NTRS)

    Anderson, D.

    1991-01-01

    Measuring similarities between large sequences of genetic information is a formidable task requiring enormous amounts of computer time. Geneticists claim that nearly two months of CRAY-2 time are required to run a single comparison of the known database against the new bases that will be found this year, and more than a CRAY-2 year for next year's genetic discoveries, and so on. The DNA IC, designed at HP-ICBD in cooperation with the California Institute of Technology and the Jet Propulsion Laboratory, is being implemented in order to move the task of genetic comparison onto workstations and personal computers, while vastly improving performance. The chip is a systolic (pumped) array comprised of 16 processors, control logic, and global RAM, totaling 400,000 FETS. At 12 MHz, each chip performs 2.7 billion 16 bit operations per second. Using 35 of these chips in series on one PC board (performing nearly 100 billion operations per second), a sequence of 560 bases can be compared against the eventual total genome of 3 billion bases, in minutes--on a personal computer. While the designed purpose of the DNA chip is for genetic research, other disciplines requiring similarity measurements between strings of 7 bit encoded data could make use of this chip as well. Cryptography and speech recognition are two examples. A mix of full custom design and standard cells, in CMOS34, were used to achieve these goals. Innovative test methods were developed to enhance controllability and observability in the array. This paper describes these techniques as well as the chip's functionality. This chip was designed in the 1989-90 timeframe.

  8. Learning by Analogy: Discriminating between Potential Analogs

    ERIC Educational Resources Information Center

    Richland, Lindsey E.; McDonough, Ian M.

    2010-01-01

    The ability to successfully discriminate between multiple potentially relevant source analogs when solving new problems is crucial to proficiency in a mathematics domain. Experimental findings in two different mathematical contexts demonstrate that providing cues to support comparative reasoning during an initial instructional analogy, relative to…

  9. Design and Facile Synthesis of New Dinucleotide Cap Analog Containing Both 2' and 3'-OH Modification on M⁷Guanosine Moiety.

    PubMed

    Kore, Anilkumar R; Bugarin, Alejandro; Shanmugasundaram, Muthian

    2015-01-01

    The first example of the synthesis of new dinucleotide cap analog containing 2('),3(')-diacetyl group on m(7)guanosine moiety is described. The desired modified cap analog, m(7,2)(')(,3)(')(-diacetyl)G[5(')]ppp[5(')]G has been obtained by the coupling reaction of triethylamine salt of m(7,2)(')(,3)(')(-diacetyl)GDP with ImGMP in presence of ZnCl2 as a catalyst in 62% yield with high purity. The structure of new cap analog has been confirmed by (1)H and (31)P NMR and mass data.

  10. Transition state analogs of 5'-methylthioadenosine nucleosidase disrupt quorum sensing.

    SciTech Connect

    Gutierrez, J.; Crowder, T; Rinaldo-Matthis, A; Ho, M; Almo, S; Schramm, V

    2009-01-01

    5'-Methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) is a bacterial enzyme involved in S-adenosylmethionine-related quorum sensing pathways that induce bacterial pathogenesis factors. Transition state analogs MT-DADMe-Immucillin-A, EtT-DADMe-Immucillin-A and BuT-DADMe-Immucillin-A are slow-onset, tight-binding inhibitors of Vibrio cholerae MTAN (VcMTAN), with equilibrium dissociation constants of 73, 70 and 208 pM, respectively. Structural analysis of VcMTAN with BuT-DADMe-Immucillin-A revealed interactions contributing to the high affinity. We found that in V. cholerae cells, these compounds are potent MTAN inhibitors with IC50 values of 27, 31 and 6 nM for MT-, EtT- and BuT-DADMe-Immucillin-A, respectively; the compounds disrupt autoinducer production in a dose-dependent manner without affecting growth. MT- and BuT-DADMe-Immucillin-A also inhibited autoinducer-2 production in enterohemorrhagic Escherichia coli O157:H7 with IC{sub 50} values of 600 and 125 nM, respectively. BuT-DADMe-Immucillin-A inhibition of autoinducer-2 production in both strains persisted for several generations and caused reduction in biofilm formation. These results support MTAN's role in quorum sensing and its potential as a target for bacterial anti-infective drug design.

  11. ESD evaluation of radiation-hardened, high-reliability CMOS and MNOS ICs

    SciTech Connect

    Soden, J.M.; Stewart, H.D.; Pastorek, R.A.

    1983-01-01

    Standard human-body-equivalent circuit electrostatic discharge (ESD) tests were performed on the inputs of high-reliability, radiation-hardened integrated circuits (ICs) designed with seven different technologies. Metal and silicon gate complementary MOS (CMOS) and metal-nitride-oxide-semiconductor (MNOS) ICs with design rules ranging from 10 microns down to 2 microns were evaluated. The ESD hardness of these ICs ranged from 1 kV to greater than 9 kV. The low-range ESD hardness ICs were fabricated with a masking polysilicon ring that defined the input protection diodes. Tests on commercial equivalent ICs demonstrated that the ESD hardness of the radiation-hardened ICs was not significantly less than the ESD hardness of the commercial equivalent ICs. The failure modes and mechanisms of the ICs were evaluated. Most of the ICs that did not have the masking polysilicon ring failed because of input to V/sub DD/ or V/sub SS/ shorts due to degraded protection diodes. ESD tests with the pulse applied between the package metal lid and the package pins were also performed. These lid tests produced permanent input damage, the same as occurred during tests with the pulse applied to the package input, but the damage occurred at lower voltages. ESD pulses with peak voltages as low as 250 volts produced arcs from the lid to the input bond wires, resulting in degraded inputs.

  12. ESD evaluation of radiation-hardened, high reliability CMOS and MNOS ICs

    SciTech Connect

    Soden, J.M.; Pastorek, R.A.; Stewart, H.D.

    1984-02-01

    Standard human body equivalent circuit electrostatic discharge (ESD) tests were performed on the inputs of high-reliability, radiation-hardened integrated circuits (ICs) designed with seven different technologies. Metal and silicon gate complementary MOS (CMOS) and metal-nitrideoxide-semiconductor (MNOS) ICs with design rules ranging from 10 microns down to 2 microns were evaluated. The ESD hardness of these ICs ranged from 1 kV to greater than 9 kV. The low range ESD hardness ICs were fabricated with a masking polysilicon ring that defined the input protection diodes. Tests on commercial equivalent ICs demonstrated that the ESD hardness of the radiation-hardened ICs was not significantly less than the ESD hardness of the commercial equivalent ICs. The failure modes and mechanisms of the ICs were evaluated. Most of the ICs that did not have the masking polysilicon ring failed because of input to V/sub DD/ or V/sub SS/ shorts due to degraded protection diodes. ESD tests with the pulse applied between the package metal lid and the package pins were also performed. These lid tests produced permanent input damage, the same as occurred during tests with the pulse applied to the package input, but the damage occurred at lower voltages. ESD pulses with peak voltages as low as 250 volts produced arcs from the lid to the input bond wires, resulting in degraded inputs.

  13. ESD evaluation of radiation-hardened, high-reliability CMOS and MNOS ICs

    NASA Astrophysics Data System (ADS)

    Soden, J. M.; Stewart, H. D.; Pastorek, R. A.

    Standard human-body-equivalent circuit electrostatic discharge (ESD) tests were performed on the inputs of high-reliability, radiation-hardened integrated circuits (ICs) designed with seven different technologies. Metal and silicon gate complementary metal oxide semiconductors (CMOS) and metal-nitride-oxide-semiconductor (MNOS) ICs with design rules ranging from 10 microns down to 2 microns were evaluated. The ESD hardness of these ICs ranged from 1 kV to greater than 9 kV. The low-range ESD hardness ICs were fabricated with a masking polysilicon ring that defined the input protection diodes. Tests on commercial equivalent ICs demonstrated that the ESD hardness of the radiation-hardened ICs was not significantly less than the ESD hardness of the commercial equivalent ICs. The failure modes and mechanisms of the ICs were evaluated. Most of the ICs that did not have the making polysilicon ring failed because of input to V sub DD or V sub SS shorts due to degraded protection diodes. ESD tests with the pulse applied between the package metal lid and the package pins were also performed. These lid tests produced permanent input damage, the same as occurred during tests with the pulse applied to the package input, but the damage occurred at lower voltages. ESD pulses with peak voltages as low as 250 volts produced arcs from the lid to the input bond wires, resulting in degraded inputs.

  14. Compaction and Circuit Extraction in the MAGIC IC Layout System

    DTIC Science & Technology

    1985-11-01

    the extractor. Thariks are also due to Randy Katz of UC Berkeley and the Fall 1Q84 VLSI design class, for their willingness to use the extractor...34Q-353. [McC84] S. P. McCormick, "EXCL: A Circuit Extractor for IC Designs", Proceedings of the £1st Design Automation Conference, 1Q84 , 624-628...Conference, 1Q84 , 137-143. (Mos81] R. C. Mosteller, "REST: A Leaf Cell Design System", in VLSI81, J. P. Gray (editor), Academic Press, 1Q81, 163-172

  15. I&C Modeling in SPAR Models

    SciTech Connect

    John A. Schroeder

    2012-06-01

    The Standardized Plant Analysis Risk (SPAR) models for the U.S. commercial nuclear power plants currently have very limited instrumentation and control (I&C) modeling [1]. Most of the I&C components in the operating plant SPAR models are related to the reactor protection system. This was identified as a finding during the industry peer review of SPAR models. While the Emergency Safeguard Features (ESF) actuation and control system was incorporated into the Peach Bottom Unit 2 SPAR model in a recent effort [2], various approaches to expend resources for detailed I&C modeling in other SPAR models are investigated.

  16. Analog pixel array detectors.

    PubMed

    Ercan, A; Tate, M W; Gruner, S M

    2006-03-01

    X-ray pixel array detectors (PADs) are generally thought of as either digital photon counters (DPADs) or X-ray analog-integrating pixel array detectors (APADs). Experiences with APADs, which are especially well suited for X-ray imaging experiments where transient or high instantaneous flux events must be recorded, are reported. The design, characterization and experimental applications of several APAD designs developed at Cornell University are discussed. The simplest design is a ;flash' architecture, wherein successive integrated X-ray images, as short as several hundred nanoseconds in duration, are stored in the detector chips for later off-chip digitization. Radiography experiments using a prototype flash APAD are summarized. Another design has been implemented that combines flash capability with the ability to continuously stream X-ray images at slower (e.g. milliseconds) rates. Progress is described towards radiation-hardened APADs that can be tiled to cover a large area. A mixed-mode PAD, design by combining many of the attractive features of both APADs and DPADs, is also described.

  17. Antarctic Space Analog Program

    NASA Technical Reports Server (NTRS)

    Palinkas, Lawrence A; Gunderson, E. K. Eric; Johnson, Jeffrey C.; Holland, Albert W.

    1998-01-01

    The primary aim of this project was to examine group dynamics and individual performance in extreme, isolated environments and identify human factors requirements for long-duration space missions using data collected in an analog environment. Specifically, we wished to determine: 1) the characteristics of social relations in small groups of individuals living and working together in extreme, isolated environments, and 2) the environmental, social and psychological determinants of performance effectiveness in such groups. These two issues were examined in six interrelated studies using data collected in small, isolated research stations in Antarctica from 1963 to the present. Results from these six studies indicated that behavior and performance on long-duration space flights is likely to be seasonal or cyclical, situational, social, and salutogenic in nature. The project responded to two NASA program emphases for FY 1997 as described in the NRA: 1) the primary emphasis of the Behavior and Performance Program on determining long-term individual and group performance responses to space, identifying critical factors affecting those responses and understanding underlying mechanisms involved in behavior and performance, and developing and using ground-based models and analogs for studying space-related behavior and performance; and 2) the emphasis of the Data Analysis Program on extended data analysis. Results from the study were used to develop recommendations for the design and development of pre-flight crew training and in-flight psychological countermeasures for long-duration manned space missions.

  18. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photo shows the progress of the S-IC test stand as of October 10, 1963. Kerosene storage tanks can be seen to the left.

  19. Construction Progress of the S-IC Test Stand Towers

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photograph, taken April 4, 1963, gives a close up look at the ever-growing four towers of the S-IC Test Stand.

  20. Construction Progress of the S-IC Test Stand Tower

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photograph, taken from ground level on May 7, 1963, gives a close look at one of the four towers legs of the S-IC test stand nearing its completed height.

  1. Construction Progress of S-IC Test Stand Towers

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photograph taken April 17, 1963, gives a look at the four tower legs of the S-IC test stand at their completed height.

  2. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photo shows the progress of the S-IC test stand as of November 20, 1963.

  3. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photo shows the progress of the S-IC test stand as of October 10, 1963. Spherical liquid hydrogen tanks can be seen to the left.

  4. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photo shows the progress of the S-IC test stand as of October 22, 1963. Spherical liquid hydrogen tanks can be seen to the left. Just to the lower front of those are the cylindrical liquid oxygen (LOX) tanks.

  5. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photo shows the progress of the S-IC test stand as of November 20, 1963.

  6. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photograph, taken May 7, 1963, gives a close look at the four concrete tower legs of the S-IC test stand at their completed height.

  7. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photo shows the progress of the S-IC test stand as of October 22, 1963. Spherical liquid hydrogen tanks can be seen to the left. Just to the lower front of those are the cylindrical liquid oxygen (LOX) tanks.

  8. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photograph taken February 25, 1963, gives a close up look at two of the ever-growing four towers of the S-IC Test Stand.

  9. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photo shows the progress of the S-IC test stand as of October 10, 1963. Kerosene storage tanks can be seen to the left.

  10. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photograph taken March 29, 1963, gives a close up look at two of the ever-growing four towers of the S-IC Test Stand.

  11. Construction Progress of the S-IC Test Stand Towers

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photograph, taken April 4, 1963, gives a close up look at the ever-growing four towers of the S-IC Test Stand.

  12. Construction Progress of S-IC Test Stand Towers

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photograph taken April 17, 1963, gives a look at the four tower legs of the S-IC test stand at their completed height.

  13. Construction Progress of the S-IC Test Stand Tower

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photograph, taken from ground level on May 7, 1963, gives a close look at one of the four towers legs of the S-IC test stand nearing its completed height.

  14. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photo shows the progress of the S-IC test stand as of October 10, 1963. Spherical liquid hydrogen tanks can be seen to the left.

  15. Radioactive Decay - An Analog.

    ERIC Educational Resources Information Center

    McGeachy, Frank

    1988-01-01

    Presents an analog of radioactive decay that allows the student to grasp the concept of half life and the exponential nature of the decay process. The analog is devised to use small, colored, plastic poker chips or counters. Provides the typical data and a graph which supports the analog. (YP)

  16. Radioactive Decay - An Analog.

    ERIC Educational Resources Information Center

    McGeachy, Frank

    1988-01-01

    Presents an analog of radioactive decay that allows the student to grasp the concept of half life and the exponential nature of the decay process. The analog is devised to use small, colored, plastic poker chips or counters. Provides the typical data and a graph which supports the analog. (YP)

  17. The Analogical Mind.

    ERIC Educational Resources Information Center

    Holyoak, Keith J.; Thagard, Paul

    1997-01-01

    The use of analogy in human thinking is examined from the perspective of a multiconstraint theory that postulates similarity, structure, and purpose as three kinds of constraints. The theory has been implemented in computational simulations of the analogical human mind using the Analogical Mapping by Constraint Satisfaction (ACME) model. (SLD)

  18. Giant Spherical Cluster with I-C140 Fullerene Topology**

    PubMed Central

    Heinl, Sebastian; Peresypkina, Eugenia; Sutter, Jörg; Scheer, Manfred

    2015-01-01

    We report on an effective cluster expansion of CuBr-linked aggregates by the increase of the steric bulk of the CpR ligand in the pentatopic molecules [CpRFe(η5-P5)]. Using [CpBIGFe(η5-P5)] (CpBIG=C5(4-nBuC6H4)5), the novel multishell aggregate [{CpBIGFe(η5:2:1:1:1:1:1-P5)}12(CuBr)92] is obtained. It shows topological analogy to the theoretically predicted I-C140 fullerene molecule. The spherical cluster was comprehensively characterized by various methods in solution and in the solid state. PMID:26411255

  19. 60 V tolerance full symmetrical switch for battery monitor IC

    NASA Astrophysics Data System (ADS)

    Zhang, Qidong; Yang, Yintang; Chai, Changchun

    2017-06-01

    For stacked battery monitoring IC high speed and high precision voltage acquisition requirements, this paper introduces a kind of symmetrical type high voltage switch circuit. This kind of switch circuit uses the voltage following structure, which eliminates the leakage path of input signals. At the same time, this circuit adopts a high speed charge pump structure, in any case the input signal voltage is higher than the supply voltage, it can fast and accurately turn on high voltage MOS devices, and convert the battery voltage to an analog to digital converter. The proposed high voltage full symmetry switch has been implemented in a 0.18 μm BCD process; simulated and measured results show that the proposed switch can always work properly regardless of the polarity of the voltage difference between the input signal ports and an input signal higher than the power supply. Project supported by the National Natural Science Foundation of China (No. 61334003).

  20. NMR investigations of structural and dynamics features of natively unstructured drug peptide - salmon calcitonin: implication to rational design of potent sCT analogs.

    PubMed

    Rawat, Atul; Kumar, Dinesh

    2013-01-01

    Backbone dynamics and conformational properties of drug peptide salmon calcitonin have been studied in aqueous solution using nuclear magnetic resonance (NMR). Although salmon calcitonin (sCT) is largely unfolded in solution (as has been reported in several circular dichroism studies), the secondary H(α) chemical shifts and three bond H(N) -H(α) coupling constants indicated that most of the residues of the peptide are populating the α-helical region of the Ramachandran (ϕ, ψ) map. Further, the peptide in solution has been found to exhibit multiple conformational states exchanging slowly on the NMR timescale (10(2) -10(3)  s(-1) ), inferred by the multiple chemical shift assignments in the region Leu4-Leu12 and around Pro23 (for residues Gln20-Tyr22 and Arg24). Possibly, these slowly exchanging multiple conformational states might inhibit symmetric self-association of the peptide and, in part, may account for its reduced aggregation propensity compared with human calcitonin (which lacks this property). The (15) N NMR-relaxation data revealed (i) the presence of slow (microsecond-to-millisecond) timescale dynamics in the N-terminal region (Cys1-Ser5) and core residues His17 and Asn26 and (ii) the presence of high frequency (nanosecond-to-picosecond) motions in the C-terminal arm. Put together, the various results suggested that (i) the flexible C-terminal of sCT (from Thr25-Thr31) is involved in identification of specific target receptors, (ii) whereas the N-terminal of sCT (from Cys1-Gln20) in solution - exhibiting significant amount of conformational plasticity and strong bias towards biologically active α-helical structure - facilitates favorable conformational adaptations while interacting with the intermembrane domains of these target receptors. Thus, we believe that the structural and dynamics features of sCT presented here will be useful guiding attributes for the rational design of biologically active sCT analogs.

  1. Analog enhancement of radiographic images

    NASA Technical Reports Server (NTRS)

    Baily, N. A.; Nachazel, R. J.

    1976-01-01

    The paper shows how analog methods for edge sharpening, contrast enhancement, and expansion of the range of gray levels of particular interest are effective for easy on-line application to video viewing of X-ray roentgenograms or to fluoroscopy. The technique for analog enhancement of radiographic images is a modified version of the system designed by Fuchs et al. (1972), whereby an all directional second derivative signal called detail signal is used to produce both vertical and horizontal enhancement of the image. Particular attention is given to noise filtration and contrast enhancement. Numerous radiographs supplement the text.

  2. Semiconductor/High-Tc-Superconductor Hybrid ICs

    NASA Technical Reports Server (NTRS)

    Burns, Michael J.

    1995-01-01

    Hybrid integrated circuits (ICs) containing both Si-based semiconducting and YBa(2)Cu(3)O(7-x) superconducting circuit elements on sapphire substrates developed. Help to prevent diffusion of Cu from superconductors into semiconductors. These hybrid ICs combine superconducting and semiconducting features unavailable in superconducting or semiconducting circuitry alone. For example, complementary metal oxide/semiconductor (CMOS) readout and memory devices integrated with fast-switching Josephson-junction super-conducting logic devices and zero-resistance interconnections.

  3. Semiconductor/High-Tc-Superconductor Hybrid ICs

    NASA Technical Reports Server (NTRS)

    Burns, Michael J.

    1995-01-01

    Hybrid integrated circuits (ICs) containing both Si-based semiconducting and YBa(2)Cu(3)O(7-x) superconducting circuit elements on sapphire substrates developed. Help to prevent diffusion of Cu from superconductors into semiconductors. These hybrid ICs combine superconducting and semiconducting features unavailable in superconducting or semiconducting circuitry alone. For example, complementary metal oxide/semiconductor (CMOS) readout and memory devices integrated with fast-switching Josephson-junction super-conducting logic devices and zero-resistance interconnections.

  4. The future impact of GaAs digital IC's

    NASA Astrophysics Data System (ADS)

    Greiling, P. T.

    1985-03-01

    A review of digital GaAs IC technology and an assessment of its future impact on gigabit signal processing is presented. High-speed signal processing and computers will require MSI-complexity interface circuits capable of 1-10 GHz clock frequencies and LSI-complexity digital circuits operating in the 0.2-5 GHz range at tens of microwatts per gate. A wide range of applications exists for frequency counters, multiplexers, A/D converters, FFT's, microprocessors, and memories that operate at speeds significantly higher than on presently available circuits. Issues related to high-speed IC design such as power dissipation, packing density, capacitance effects, design rules, and intra- and interchip propagation delays are discussed.

  5. Robust hyperchaotic synchronization via analog transmission line

    NASA Astrophysics Data System (ADS)

    Sadoudi, S.; Tanougast, C.

    2016-02-01

    In this paper, a novel experimental chaotic synchronization technique via analog transmission is discussed. We demonstrate through Field-Programmable Gate Array (FPGA) implementation design the robust synchronization of two embedded hyperchaotic Lorenz generators interconnected with an analog transmission line. The basic idea of this work consists in combining a numerical generation of chaos and transmitting it with an analog signal. The numerical chaos allows to overcome the callback parameter mismatch problem and the analog transmission offers robust data security. As application, this technique can be applied to all families of chaotic systems including time-delayed chaotic systems.

  6. Rat Hormone Sensitive Lipase Inhibition by Cyclipostins and Their Analogs

    PubMed Central

    Vasilieva, Elena; Dutta, Supratik; Malla, Raj K.; Martin, Benjamin P.; Spilling, Christopher D.; Dupureur, Cynthia M.

    2015-01-01

    Cyclipostins are bicyclic lipophilic phosphate natural products. We report here that synthesized individual diastereomers of cyclipostins P and R have nanomolar IC50s toward hormone sensitive lipase (HSL). The less potent diastereomers of these compounds have 10-fold weaker IC50s. The monocyclic phosphate analog of cyclipostin P is nearly as potent as the bicyclic natural product. Bicyclic phosphonate analogs of both cyclipostins exhibit IC50s similar to those of the weaker diastereomer phosphates (about 400 nM). The monocyclic phosphonate analog of cyclipostin P has similar potency. A series of monocyclic phosphonate analogs in which a hydrophobic tail extends from the lactone side of the ring are considerably poorer inhibitors, with IC50s around 50 μM. Finally cyclophostin, a related natural product inhibitor of acetylcholinesterase (AChE) that lacks the hydrocarbon tail of cyclipostins, is not active against HSL. These results indicate a critical SAR for these compounds, the hydrophobic tail. The smaller lactone ring is not critical to activity, a similarity shared with cyclophostin and AChE. The HSL kinetics of inhibition for the cyclipostin P trans diastereomer were examined in detail. The reaction is irreversible with a KI of 40 nM and a rate constant for inactivation of 0.2 min−1. These results are similar to those observed for cyclophostin and AChE. PMID:25678014

  7. Mars inflatable greenhouse analog.

    PubMed

    Sadler, Philip D; Giacomelli, Gene A

    2002-01-01

    Light intensities on the Martian surface can possibly support a bioregenerative life support system (BLSS) utilizing natural sunlight for hydroponic crop production, if a suitable controlled environment can be provided. Inflatable clear membrane structures offer low mass, are more easily transported than a rigid structure, and are good candidates for providing a suitable controlled environment for crop production. Cable culture is one hydroponic growing system that can take advantage of the beneficial attributes of the inflatable structure. An analog of a Mars inflatable greenhouse can provide researchers data on issues such as crew time requirements for operation, productivity for BLSS, human factors, and much more at a reasonable cost. This is a description of one such design.

  8. Biomimetic Analogs for Collagen Biomineralization

    PubMed Central

    Gu, L.; Kim, Y.K.; Liu, Y.; Ryou, H.; Wimmer, C.E.; Dai, L.; Arola, D.D.; Looney, S.W.; Pashley, D.H.; Tay, F.R.

    2011-01-01

    Inability of chemical phosphorylation of sodium trimetaphosphate to induce intrafibrillar mineralization of type I collagen may be due to the failure to incorporate a biomimetic analog to stabilize amorphous calcium phosphates (ACP) as nanoprecursors. This study investigated adsorption/desorption characteristics of hydrolyzed and pH-adjusted sodium trimetaphosphate (HPA-Na3P3O9) to collagen. Based on those results, a 5-minute treatment time with 2.8 wt% HPA-Na3P3O9 was used in a single-layer reconstituted collagen model to confirm that both the ACP-stabilization analog and matrix phosphoprotein analog must be present for intrafibrillar mineralization. The results of that model were further validated by complete remineralization of phosphoric-acid-etched dentin treated with the matrix phosphoprotein analog and lined with a remineralizing lining composite, and with the ACP-stabilization analog supplied in simulated body fluid. An understanding of the basic processes involved in intrafibrillar mineralization of reconstituted collagen fibrils facilitates the design of novel tissue engineering materials for hard tissue repair and regeneration. PMID:20940362

  9. Pharmacokinetic-Pharmacodynamic Analysis of Spiroindolone Analogs and KAE609 in a Murine Malaria Model

    PubMed Central

    Freymond, Céline; Fischli, Christoph; Yu, Jing; Weber, Sebastian; Goh, Anne; Yeung, Bryan K. S.; Ho, Paul C.; Dartois, Véronique; Diagana, Thierry T.; Rottmann, Matthias

    2014-01-01

    Limited information is available on the pharmacokinetic (PK) and pharmacodynamic (PD) parameters driving the efficacy of antimalarial drugs. Our objective in this study was to determine dose-response relationships of a panel of related spiroindolone analogs and identify the PK-PD index that correlates best with the efficacy of KAE609, a selected class representative. The dose-response efficacy studies were conducted in the Plasmodium berghei murine malaria model, and the relationship between dose and efficacy (i.e., reduction in parasitemia) was examined. All spiroindolone analogs studied displayed a maximum reduction in parasitemia, with 90% effective dose (ED90) values ranging between 6 and 38 mg/kg of body weight. Further, dose fractionation studies were conducted for KAE609, and the relationship between PK-PD indices and efficacy was analyzed. The PK-PD indices were calculated using the in vitro potency against P. berghei (2× the 99% inhibitory concentration [IC99]) as a threshold (TRE). The percentage of the time in which KAE609 plasma concentrations remained at >2× the IC99 within 48 h (%T>TRE) and the area under the concentration-time curve from 0 to 48 h (AUC0–48)/TRE ratio correlated well with parasite reduction (R2 = 0.97 and 0.95, respectively) but less so for the maximum concentration of drug in serum (Cmax)/TRE ratio (R2 = 0.88). The present results suggest that for KAE609 and, supposedly, for its analogs, the dosing regimens covering a T>TRE of 100%, AUC0–48/TRE ratio of 587, and a Cmax/TRE ratio of 30 are likely to result in the maximum reduction in parasitemia in the P. berghei malaria mouse model. This information could be used to prioritize analogs within the same class of compounds and contribute to the design of efficacy studies, thereby facilitating early drug discovery and lead optimization programs. PMID:25487807

  10. The Effect of Analogy-Based Teaching on Students' Achievement and Students' Views about Analogies

    ERIC Educational Resources Information Center

    Genc, Murat

    2013-01-01

    The purpose of this study is to determine the effect of the analogy-based teaching on students' achievement and students' views about analogies. In this research, Solomon group design which is one of the experimental designs, was implemented. The sample of the research consists of 108 students in four 6th grade classes in Turkey. The achievement…

  11. The Effect of Analogy-Based Teaching on Students' Achievement and Students' Views about Analogies

    ERIC Educational Resources Information Center

    Genc, Murat

    2013-01-01

    The purpose of this study is to determine the effect of the analogy-based teaching on students' achievement and students' views about analogies. In this research, Solomon group design which is one of the experimental designs, was implemented. The sample of the research consists of 108 students in four 6th grade classes in Turkey. The achievement…

  12. Analysis of the degradation mechanisms of MHC class I-presented tumor antigenic peptides by high performance liquid chromatography/electrospray ionization mass spectrometry: application to the design of peptidase-resistant analogs.

    PubMed

    Ayyoub, M; Monsarrat, B; Mazarguil, H; Gairin, J E

    1998-01-01

    Peptide vaccines based on the use of MHC class I restricted epitopes are currently assayed for anti-tumor and anti-viral immunotherapy. With the aim of designing minimally modified, peptidase-resistant analogs, we developed a rational approach based on a detailed understanding of the degradation mechanism of peptides in serum. Degradation of murine tumor antigen P198 and human tumor antigen MAGE-3.A1 was followed by on line high performance liquid chromatography/electrospray ionization mass spectrometry (HPLC/ESI-MS). This method provided high precision and sensitivity for rapid and direct analysis of degradation fragments in a complex mixture and, very importantly, precise identification of transient degradation fragments present at low concentrations. The design of structurally modified analogs, and the analysis of their degradation by on-line HPLC/ESI-MS, allowed us to to demonstrate the efficiency of local modifications in the protection of a given peptide bond towards a specific peptidase activity.

  13. Silicon MCM substrates for integration of III-V photonic devices and CMOS IC`s

    SciTech Connect

    Seigal, P.; Carson, R.; Flores, R.; Rose, B.

    1993-07-01

    The progress made in advanced packaging development at Sandia National Laboratories for integration of III-V photonic devices and CMOS IC`s on Silicon MCM substrates for planar aid stacked applications will be reported. Studies to characterize precision alignment techniques using solder attach materials compatible with both silicon IC`s and III-V devices will be discussed. Examples of the use of back-side alignment and IR through-wafer inspection will be shown along with the extra processing steps that are used. Under bump metallurgy considerations are also addressed.

  14. A 128-channel 6 mW wireless neural recording IC with spike feature extraction and UWB transmitter.

    PubMed

    Chae, Moo Sung; Yang, Zhi; Yuce, Mehmet R; Hoang, Linh; Liu, Wentai

    2009-08-01

    This paper reports a 128-channel neural recording integrated circuit (IC) with on-the-fly spike feature extraction and wireless telemetry. The chip consists of eight 16-channel front-end recording blocks, spike detection and feature extraction digital signal processor (DSP), ultra wideband (UWB) transmitter, and on-chip bias generators. Each recording channel has amplifiers with programmable gain and bandwidth to accommodate different types of biological signals. An analog-to-digital converter (ADC) shared by 16 amplifiers through time-multiplexing results in a balanced trade-off between the power consumption and chip area. A nonlinear energy operator (NEO) based spike detector is implemented for identifying spikes, which are further processed by a digital frequency-shaping filter. The computationally efficient spike detection and feature extraction algorithms attribute to an auspicious DSP implementation on-chip. UWB telemetry is designed to wirelessly transfer raw data from 128 recording channels at a data rate of 90 Mbit/s. The chip is realized in 0.35 mum complementary metal-oxide-semiconductor (CMOS) process with an area of 8.8 x 7.2 mm(2) and consumes 6 mW by employing a sequential turn-on architecture that selectively powers off idle analog circuit blocks. The chip has been tested for electrical specifications and verified in an ex vivo biological environment.

  15. Animal experiments with the microelectronics neural bridge IC.

    PubMed

    Li, Wenyuan; Pei, Fei; Wang, Zhigong; Lü, Xiaoying

    2012-01-01

    The combination of the neural science and the microelectronics science offers a new way to restore the function of central nervous system. A neural regeneration module is used to be implanted into body to bridge the damaged nerve. A microelectronics neural bridge IC designed in CSMC 0.5□m CMOS process which can detect the neural signal and stimulate the nerve is presented. The neural regeneration module is composed of the microelectronics neural bridge IC and some discrete devices. An animal experiment has been done to check whether the neural signal can be transmitted with the chip normally or not. The animal experiment results suggest that the neural regeneration module can make the neural signal transmit normally.

  16. Analog Frame Store Memory.

    DTIC Science & Technology

    1980-01-15

    information in analog form for periods up to ten (i0)seconds. The storage element is a state-of-the-art monolithic charge coupled device (CCD) which...Analog Field Storage Device The Analog Field Storage Device is a solid state monolithic array operating on the "charge coupled" principle. It consists...the implementation of the corrective action. A three-month slip in delivery of the full system will result with integration test taking place in June

  17. Nonvolatile Analog Memory

    NASA Technical Reports Server (NTRS)

    MacLeod, Todd C. (Inventor)

    2007-01-01

    A nonvolatile analog memory uses pairs of ferroelectric field effect transistors (FFETs). Each pair is defined by a first FFET and a second FFET. When an analog value is to be stored in one of the pairs, the first FFET has a saturation voltage applied thereto, and the second FFET has a storage voltage applied thereto that is indicative of the analog value. The saturation and storage voltages decay over time in accordance with a known decay function that is used to recover the original analog value when the pair of FFETs is read.

  18. Analog without fear

    NASA Technical Reports Server (NTRS)

    Delagrange, A. D.

    1977-01-01

    Analog circuitry, also referred to as Linear, has been nearly run over by the digital/computer bandwagon. This is unfortunate because tremendous advances are being made in the field of analog integrated circuitry. Each year's progress raises the state-of-the-art, bringing achievements not possible even the year before. Many of the traditional prejudices against analog circuitry are no longer valid. This report attempts to summarize what is available now and what can (and can't) be done with analog integrated circuitry.

  19. The H II regions of IC 1613

    SciTech Connect

    Price, J.S.; Mason, S.F.; Gullixson, C.A. Prime Computer, Inc., Bedford, MA Lowell Observatory, Flagstaff, AZ )

    1990-08-01

    New H-alpha images are presented of IC 1613, a small irregular galaxy in the Local Group. The images, obtained with a CCD on the 42-in telescope at Lowell Observatory, have been calibrated and used to produce an H-alpha luminosity function and a size distribution for the H II regions in IC 1613. The results are compared to results for NGC 6822 and the Magellanic Clouds. The size distribution is found to be Poissonian over a limited range. 24 refs.

  20. Saturn V S-IC (First) Stage

    NASA Technical Reports Server (NTRS)

    1967-01-01

    This illustration shows a cutaway drawing with callouts of the major components for the S-IC (first) stage of the Saturn V launch vehicle. The S-IC stage is 138 feet long and 33 feet in diameter, producing more than 7,500,000 pounds of thrust through five F-1 engines powered by liquid oxygen and kerosene. Four of the engines are mounted on an outer ring and gimball for control purposes. The fifth engine is rigidly mounted in the center. When ignited, the roar produced by the five engines equals the sound of 8,000,000 hi-fi sets.

  1. Saturn V S-IC (First) Stage

    NASA Technical Reports Server (NTRS)

    1968-01-01

    This is a cutaway view of the Saturn V first stage, known as the S-IC, detailing the five F-1 engines and fuel cells. The S-IC stage is 138 feet long and 33 feet in diameter, producing more than 7,500,000 pounds of thrust through the five F-1 engines that are powered by liquid oxygen and kerosene. Four of the engines are mounted on an outer ring and gimbal for control purposes. The fifth engine is rigidly mounted in the center. When ignited, the roar produced by the five engines equals the sound of 8,000,000 hi-fi sets.

  2. Saturn V S-IC (First) Stage

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This cutaway illustration shows the Saturn V S-IC (first) stage with detailed callouts of the components. The S-IC Stage is 138 feet long and 33 feet in diameter, producing 7,500,000 pounds of thrust through five F-1 engines that are powered by liquid oxygen and kerosene. Four of the engines are mounted on an outer ring and gimbal for control purposes. The fifth engine is rigidly mounted in the center. When ignited, the roar produced by the five engines equals the sound of 8,000,000 hi-fi sets.

  3. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1961-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photo, taken September 5, 1961, shows pumps used for extracting water emerging form a disturbed natural spring that occurred during the excavation of the site. The pumping became a daily ritual and the site is still pumped today.

  4. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1961-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photo, taken September 5, 1961, shows pumps used for extracting water emerging form a disturbed natural spring that occurred during the excavation of the site. The pumping became a daily ritual and the site is still pumped today.

  5. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. In this photo, taken June 24, 1963, the four tower legs of the test stand can be seen at their maximum height.

  6. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photo, depicts the progress of the stand as of January 14, 1963, with its four towers prominently rising.

  7. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1962-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This construction photo depicts the progress of the stand site as of October 8, 1962.

  8. Experiments on Evolving Software Models of Analog Circuits

    NASA Technical Reports Server (NTRS)

    Lohn, Jason D.

    1999-01-01

    Analog circuits are of great importance in electronic system design since the world is fundamentally analog in nature. While the amount of digital design activity far outpaces that of analog design, most digital systems require analog modules for interfacing with the external world. It was recently estimated that approximately 60% of digital application- specific integrated circuit designs incorporated analog circuits. With challenging analog circuit design problems and few analog design engineers, there are economic reasons for automating the analog design process, especially time-to-market considerations. Techniques for analog circuit design automation began appearing about two decades ago. These methods incorporated heuristics [6], knowledge bases [1], simulated annealing [5], and other algorithms. Efforts using techniques from evolutionary computation began appearing over the last few years. These include the use of genetic algorithms to select electronic component values (for example, the resistance value of a resistor), to select circuit topologies, and to design amplifiers using a limited set of canned topologies [4]. A genetic programming-based analog circuit design system has been demonstrated in which the circuit sizes, component values, and the circuit topologies are determined automatically [3]. The genetic-algorithm systems typically represent circuit structures as vectors of parameters encoded in binary strings, while the genetic programming system manipulates tree data structures.

  9. Experiments on Evolving Software Models of Analog Circuits

    NASA Technical Reports Server (NTRS)

    Lohn, Jason D.

    1999-01-01

    Analog circuits are of great importance in electronic system design since the world is fundamentally analog in nature. While the amount of digital design activity far outpaces that of analog design, most digital systems require analog modules for interfacing with the external world. It was recently estimated that approximately 60% of digital application- specific integrated circuit designs incorporated analog circuits. With challenging analog circuit design problems and few analog design engineers, there are economic reasons for automating the analog design process, especially time-to-market considerations. Techniques for analog circuit design automation began appearing about two decades ago. These methods incorporated heuristics [6], knowledge bases [1], simulated annealing [5], and other algorithms. Efforts using techniques from evolutionary computation began appearing over the last few years. These include the use of genetic algorithms to select electronic component values (for example, the resistance value of a resistor), to select circuit topologies, and to design amplifiers using a limited set of canned topologies [4]. A genetic programming-based analog circuit design system has been demonstrated in which the circuit sizes, component values, and the circuit topologies are determined automatically [3]. The genetic-algorithm systems typically represent circuit structures as vectors of parameters encoded in binary strings, while the genetic programming system manipulates tree data structures.

  10. A wideband analog correlating spectrometer for millimeter astronomy

    NASA Astrophysics Data System (ADS)

    Goeller, Robert E.

    2007-08-01

    This project developed an analog correlating spectrometer intended for use in millimeter Astronomy. It is based in part on the Wideband Analog Spectrometers (WASP and WASP-II) built by Harris, et al (See Harris, et al, (1998), and Harris and Zmuidzinas, (2001)). Like WASP, we use tapped microstrip traces etched on a circuit board as delay lines to produce the autocorrelation function (ACF) of the incoming signal. We then get the spectrum by taking the Fourier Transform of the ACF. A major innovation of our design is the use of a single delay line (per segment) where the signal to be analyzed is launched on to the same delay line from either end. We produce the discrete autocorrelation function of the incoming signal via resistive taps coupled to detector diodes. Multiplication of the signals from each end is accomplished using the detector diode characteristics, along with phase switches and synchronous detectors, eliminating the need for expensive Gilbert Cell multipliers. We designed, built, and tested a complete prototype system with a bandwidth of 6.7 GHz and a resolution of 31 MHz. In this work we describe the detailed design, operation and performance of the prototype spectrometer. The work culminated with the observation of several nearby galaxies; M82, NGC253, IC342 and NGC1068 as well as Sagittarius B2 and Venus, using the prototype spectrometer. We used the FCRAO 14 meter radio telescope with the SEQUOIA receiver, which covers from 85 to 115.5 GHz. Our observations produced continuous spectra over 4 bands, giving near continuous coverage from 86 GHz to 115.5 GHz.

  11. Analogs of the marine alkaloid makaluvamines: synthesis, topoisomerase II inhibition, and anticancer activity.

    PubMed

    Shinkre, Bidhan A; Raisch, Kevin P; Fan, Liming; Velu, Sadanandan E

    2007-05-15

    Twelve analogs of makaluvamines have been synthesized. These compounds were evaluated for their ability to inhibit the enzyme topoisomerase II. Five compounds were shown to inhibit topoisomerase catalytic activity comparable to two known topoisomerase II targeting control drugs, etoposide and m-AMSA. Their cytotoxicity against human colon cancer cell line HCT-116 and human breast cancer cell lines MCF-7 and MDA-MB-468 has been evaluated. Four makaluvamine analogs exhibited better IC(50) values against HCT-116 as compared to control drug etoposide. One analog exhibited better IC(50) value against HCT-116 as compared to m-AMSA. All 12 of the makaluvamine analogs exhibited better IC(50) values against MCF-7 and MDA-MB-468 as compared to etoposide as well as m-AMSA.

  12. Structure-guided design of fluorescent S-adenosylmethionine analogs for a high-throughput screen to target SAM-I riboswitch RNAs.

    PubMed

    Hickey, Scott F; Hammond, Ming C

    2014-03-20

    Many classes of S-adenosylmethionine (SAM)-binding RNAs and proteins are of interest as potential drug targets in diverse therapeutic areas, from infectious diseases to cancer. In the former case, the SAM-I riboswitch is an attractive target because this structured RNA element is found only in bacterial mRNAs and regulates multiple genes in several human pathogens. Here, we describe the synthesis of stable and fluorescent analogs of SAM in which the fluorophore is introduced through a functionalizable linker to the ribose. A Cy5-labeled SAM analog was shown to bind several SAM-I riboswitches via in-line probing and fluorescence polarization assays, including one from Staphylococcus aureus that controls the expression of SAM synthetase in this organism. A fluorescent ligand displacement assay was developed and validated for high-throughput screening of compounds to target the SAM-I riboswitch class. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Exploiting Electrocorticographic Spectral Characteristics for Optimized Signal Chain Design: A 1.08 Analog Front End With Reduced ADC Resolution Requirements.

    PubMed

    Smith, William A; Mogen, Brian J; Fetz, Eberhard E; Sathe, Visvesh S; Otis, Brian P

    2016-12-01

    Electrocorticography (ECoG) is an important area of research for Brain-Computer Interface (BCI) development. ECoG, along with some other biopotentials, has spectral characteristics that can be exploited for more optimal front-end performance than is achievable with conventional techniques. This paper optimizes noise performance of such a system and discusses an equalization technique that reduces the analog-to-digital converter (ADC) dynamic range requirements and eliminates the need for a variable gain amplifier (VGA). We demonstrate a fabricated prototype in 1p9m 65 nm CMOS that takes advantage of the presented findings to achieve high-fidelity, full-spectrum ECoG recording. It requires 1.08 μW over a 150 Hz bandwidth for the entire analog front end and only 7 bits of ADC resolution.

  14. Two possible active supernovae in IC 2150

    NASA Astrophysics Data System (ADS)

    Parker, Stu; Bock, Greg; Marples, Peter; Drescher, Colin; Pearl, Patrick; BOSS Team; Contreras, Carlos; Phillips, Mark; Morrell, Nidia; Hsiao, Eric; Carnegie Supernova Project

    2016-03-01

    Stu Parker and the BOSS team report the discovery of a rare event involving two possible active supernovae in IC 2150 (z=0.010404; NED) which were recorded in images obtained by Stu Parker during the ongoing program by the Backyard Observatory Supernova Search (BOSS) team.

  15. ICS: An Intelligent Vocational Guidance Counseling System.

    ERIC Educational Resources Information Center

    Lorton, Paul, Jr.; And Others

    Computerized career guidance systems hold the promise of providing a breadth and depth of information for which counselors are not suited. At the Institute for Mathematical Studies in the Social Sciences, Stanford University, an individualized counseling system (ICS) is being developed which integrates advanced techniques from comptuer assisted…

  16. Measurement selection for parametric IC fault diagnosis

    NASA Technical Reports Server (NTRS)

    Wu, A.; Meador, J.

    1991-01-01

    Experimental results obtained with the use of measurement reduction for statistical IC fault diagnosis are described. The reduction method used involves data pre-processing in a fashion consistent with a specific definition of parametric faults. The effects of this preprocessing are examined.

  17. IC Fabrication Methods Improve Laser Diodes

    NASA Technical Reports Server (NTRS)

    Miller, M.; Pickhardt, V.

    1984-01-01

    Family of high-performance, tunable diode lasers developed for use as local oscillators in passive laser heterodyne spectrometer. Diodes fabricated using standard IC processes include photolithography, selective etching and vacuum deposition of metals and insulators. Packaging refinements improved thermal-cycling characteristics of diodes and increased room-temperature shelf life.

  18. IC Engine Applications of Carbon-Carbon

    NASA Technical Reports Server (NTRS)

    Northam, G. Burton; Rivers, H. Kevin

    2000-01-01

    Many of the properties of carbon-carbon make it an ideal material for reciprocating materials of intermittent combustion (IC) engines. Recent diesel engine tests, shown herein, indicate that the thermal and mechanical properties of carbon-carbon are adequate for piston applications, However, reducing the manufacturing costs and providing long term oxidation protection are still issues that need to be addressed.

  19. Parametric Model Checking with VerICS

    NASA Astrophysics Data System (ADS)

    Knapik, Michał; Niewiadomski, Artur; Penczek, Wojciech; Półrola, Agata; Szreter, Maciej; Zbrzezny, Andrzej

    The paper presents the verification system verICS, extended with the three new modules aimed at parametric verification of Elementary Net Systems, Distributed Time Petri Nets, and a subset of UML. All the modules exploit Bounded Model Checking for verifying parametric reachability and the properties specified in the logic PRTECTL - the parametric extension of the existential fragment of CTL.

  20. Analogies for Avogadro's Number.

    ERIC Educational Resources Information Center

    Poskozim, Paul S.; And Others

    1986-01-01

    Reviews analogies used to try to capture the concept of the magnitude of Avogadro's number, including analogies related to small/tiny objects, counting, people, water, and money. Also presents several new ones which are based on modern computers and printers. (JN)

  1. Challenges in Using Analogies

    ERIC Educational Resources Information Center

    Lin, Shih-Yin; Singh, Chandralekha

    2011-01-01

    Learning physics requires understanding the applicability of fundamental principles in a variety of contexts that share deep features. One way to help students learn physics is via analogical reasoning. Students can be taught to make an analogy between situations that are more familiar or easier to understand and another situation where the same…

  2. Challenges in Using Analogies

    ERIC Educational Resources Information Center

    Lin, Shih-Yin; Singh, Chandralekha

    2011-01-01

    Learning physics requires understanding the applicability of fundamental principles in a variety of contexts that share deep features. One way to help students learn physics is via analogical reasoning. Students can be taught to make an analogy between situations that are more familiar or easier to understand and another situation where the same…

  3. Hydraulic Capacitor Analogy

    ERIC Educational Resources Information Center

    Baser, Mustafa

    2007-01-01

    Students have difficulties in physics because of the abstract nature of concepts and principles. One of the effective methods for overcoming students' difficulties is the use of analogies to visualize abstract concepts to promote conceptual understanding. According to Iding, analogies are consistent with the tenets of constructivist learning…

  4. Training in Analogical Reasoning.

    ERIC Educational Resources Information Center

    Alexander, Patricia A.; And Others

    1987-01-01

    Experiments involving a componential approach to analogy training were conducted with 36 fourth, 34 eighth, and 96 tenth graders. Results indicate a significant positive effect on all students' verbal analogy skills and no significant effect on fourth graders' inferential skills. In-class training and reading/language arts instruction implications…

  5. Hydraulic Capacitor Analogy

    ERIC Educational Resources Information Center

    Baser, Mustafa

    2007-01-01

    Students have difficulties in physics because of the abstract nature of concepts and principles. One of the effective methods for overcoming students' difficulties is the use of analogies to visualize abstract concepts to promote conceptual understanding. According to Iding, analogies are consistent with the tenets of constructivist learning…

  6. Analog pulse processor

    DOEpatents

    Wessendorf, Kurt O.; Kemper, Dale A.

    2003-06-03

    A very low power analog pulse processing system implemented as an ASIC useful for processing signals from radiation detectors, among other things. The system incorporates the functions of a charge sensitive amplifier, a shaping amplifier, a peak sample and hold circuit, and, optionally, an analog to digital converter and associated drivers.

  7. TDR method for determine IC's parameters

    NASA Astrophysics Data System (ADS)

    Timoshenkov, V.; Rodionov, D.; Khlybov, A.

    2016-12-01

    Frequency domain simulation is a widely used approach for determine integrated circuits parameters. This approach can be found in most of software tools used in IC industry. Time domain simulation approach shows intensive usage last years due to some advantages. In particular it applicable for analysis of nonlinear and nonstationary systems where frequency domain is inapplicable. Resolution of time domain systems allow see heterogeneities on distance 1mm, determine it parameters and properties. Authors used approach based on detecting reflected signals from heterogeneities - time domain reflectometry (TDR). Field effect transistor technology scaling up to 30-60nm gate length and 10nm gate dielectric, heterojunction bi-polar transistors with 10-30nm base width allows fabricate digital IC's with 20GHz clock frequency and RF-IC's with tens GHz bandwidth. Such devices and operation speed suppose transit signal by use microwave lines. There are local heterogeneities can be found inside of the signal path due to connections between different parts of signal lines (stripe line-RF-connector pin, stripe line - IC package pin). These heterogeneities distort signals that cause bandwidth decrease for RF-devices. Time domain research methods of transmission and reflected signals give the opportunities to determine heterogeneities, it properties, parameters and built up equivalent circuits. Experimental results are provided and show possibility for inductance and capacitance measurement up to 25GHz. Measurements contains result of signal path research on IC and printed circuit board (PCB) used for 12GHz RF chips. Also dielectric constant versus frequency was measured up to 35GHz.

  8. Engineering information on an Analog Signal to Discrete Time Interval Converter (ASDT-IC)

    NASA Technical Reports Server (NTRS)

    Schwarz, F. C.

    1974-01-01

    An electronic control system for nondissipative dc power converters is presented which improves (1) the routinely attainable static output voltage accuracy to the order of + or - 1% for ambient temperatures from -55 to 100 C and (2) the dynamic stability by utilizing approximately one tenth of the feedback gain needed otherwise. Performance is due to a functional philosophy of deterministic pulse modulation based on pulse area control and to an autocompensated signal processing principle. The system can be implemented with commercially available unselected components.

  9. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. In the early stages of excavation, a natural spring was disturbed that caused a water problem which required constant pumping from the site and is even pumped to this day. Behind this reservoir of pumped water is the S-IC test stand boasting its ever-growing four towers as of March 29, 1963.

  10. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. In addition to the stand itself, related facilities were constructed during this time. Built to the northeast of the stand was a newly constructed Pump House. Its function was to provide water to the stand to prevent melting damage during testing. The water was sprayed through small holes in the stand's 1900 ton flame deflector at the rate of 320,000 gallons per minute. In this photo of the S-IC test stand, taken October 2, 1963, the flame deflector can be seen in the bottom center portion

  11. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. In addition to the stand itself, related facilities were constructed during this time. Built to the northeast of the stand was a newly constructed Pump House. Its function was to provide water to the stand to prevent melting damage during testing. The water was sprayed through small holes in the stand's 1900 ton flame deflector at the rate of 320,000 gallons per minute. In this photo of the S-IC test stand, taken September 25, 1963, the flame deflector can be seen rotated to the outside on

  12. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. In addition to the stand itself, related facilities were constructed during this time. Built to the northeast of the stand was a newly constructed Pump House. Its function was to provide water to the stand to prevent melting damage during testing. The water was sprayed through small holes in the stand's 1900 ton flame deflector at the rate of 320,000 gallons per minute. In this photo of the S-IC test stand, taken October 2, 1963, the flame deflector can be seen in the bottom center portion

  13. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. In addition to the stand itself, related facilities were constructed during this time. Built to the northeast of the stand was a newly constructed Pump House. Its function was to provide water to the stand to prevent melting damage during testing. The water was sprayed through small holes in the stand's 1900 ton flame deflector at the rate of 320,000 gallons per minute. In this photo of the S-IC test stand, taken September 25, 1963, the flame deflector can be seen rotated to the outside on

  14. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. In the early stages of excavation, a natural spring was disturbed that caused a water problem which required constant pumping from the site and is even pumped to this day. Behind this reservoir of pumped water is the S-IC test stand boasting its ever-growing four towers as of March 29, 1963.

  15. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. In addition to the stand itself, related facilities were constructed during this time. Built northeast of the stand was a newly constructed Pump House. Its function was to provide water to the stand to prevent melting damage during testing. The water was sprayed through small holes in the stand's 1900 ton flame deflector at the rate of 320,000 gallons per minute. In this photo, taken September 5, 1963, the flame deflector is being installed in the S-IC test stand.

  16. Meat analog: a review.

    PubMed

    Malav, O P; Talukder, S; Gokulakrishnan, P; Chand, S

    2015-01-01

    The health-conscious consumers are in search of nutritious and convenient food item which can be best suited in their busy life. The vegetarianism is the key for the search of such food which resembles the meat in respect of nutrition and sensory characters, but not of animal origin and contains vegetable or its modified form, this is the point when meat analog evolved out and gets shape. The consumers gets full satisfaction by consumption of meat analog due to its typical meaty texture, appearance and the flavor which are being imparted during the skilled production of meat analog. The supplement of protein in vegetarian diet through meat alike food can be fulfilled by incorporating protein-rich vegetative food grade materials in meat analog and by adopting proper technological process which can promote the proper fabrication of meat analog with acceptable meat like texture, appearance, flavor, etc. The easily available vegetables, cereals, and pulses in India have great advantages and prospects to be used in food products and it can improve the nutritional and functional characters of the food items. The various form and functional characters of food items are available world over and attracts the meat technologists and the food processors to bring some innovativeness in meat analog and its presentation and marketability so that the acceptability of meat analog can be overgrown by the consumers.

  17. Triazole-containing monophosphate mRNA cap analogs as effective translation inhibitors.

    PubMed

    Piecyk, Karolina; Lukaszewicz, Maciej; Darzynkiewicz, Edward; Jankowska-Anyszka, Marzena

    2014-10-01

    Synthetic analogs of the 5' end of mRNA (cap structure) are widely used in molecular studies on mechanisms of cellular processes such as translation, intracellular transport, splicing, and turnover. The best-characterized cap binding protein is translation initiation factor 4E (eIF4E). Recognition of the mRNA cap by eIF4E is a critical, rate-limiting step for efficient translation initiation and is considered a major target for anticancer therapy. Here, we report a facile methodology for the preparation of N2-triazole-containing monophosphate cap analogs and present their biological evaluation as inhibitors of protein synthesis. Five analogs possessing this unique hetero-cyclic ring spaced from the m7-guanine of the cap structure at a distance of one or three carbon atoms and/or additionally substituted by various groups containing the benzene ring were synthesized. All obtained compounds turned out to be effective translation inhibitors with IC50 similar to dinucleotide triphosphate m(7)GpppG. As these compounds possess a reduced number of phosphate groups and, thereby, a negative charge, which may support their cell penetration, this type of cap analog might be promising in terms of designing new potential therapeutic molecules. In addition, an exemplary dinucleotide from a corresponding mononucleotide containing benzyl substituted 1,2,3-triazole was prepared and examined. The superior inhibitory properties of this analog (10-fold vs. m(7)GpppG) suggest the usefulness of such compounds for the preparation of mRNA transcripts with high translational activity. © 2014 Piecyk et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  18. Design, synthesis, and biological evaluation of novel 1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-3-carboxamide analogs in MCF-7 and MDA-MB-468 breast cancer cell lines.

    PubMed

    Kim, Ye Jin; Pyo, Jae Sung; Jung, Young-Suk; Kwak, Jae-Hwan

    2017-02-01

    A series of novel 1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-3-carboxamide analogs were designed and synthesized for developing pyrazinoindolone scaffolds as anti-breast cancer agents. Compounds 1h and 1i, having a furan-2-yl-methylamide and benzylamide group, respectively, exhibited more potent cytotoxicity in MDA-MB-468 triple-negative breast cancer (TNBC) cells than compounds possessing aliphatic groups. Compounds 2a and 2b, as (R)-enantiomers of 1h and 1i, also had inhibitory activity against MDA-MB-468 cells. Moreover, analogs (3a-b and 3d-e) bearing a benzyl group at the N-2 position showed more potent activity than gefitinib, as a potent EFGR-TK inhibitor. Especially, compound 3a exhibited selective cytotoxic activity against MDA-MB-468 cells; it also had a synergistic effect in combination with gefitinib against MDA-MB-468 cells. In addition, we confirmed that compounds 3a and 3d inhibit phosphorylation of Akt in MDA-MB-468 cells using western blot analysis. Therefore, these 1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-3-carboxamide analogs may be helpful for investigating new anti-TNBC agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Recent Progress in Laboratory Astrophysics and Astrochemistry Achieved with the COSmIC Facility

    NASA Technical Reports Server (NTRS)

    Salama, Farid; Sciamma-O'Brien, Ella; Bejaoui, Salma

    2017-01-01

    We describe the characteristics and the capabilities of the laboratory facility, COSmIC, that was developed at NASA Ames to generate, process and analyze interstellar, circumstellar and planetary analogs in the laboratory. COSmIC stands for "Cosmic Simulation Chamber" and is dedicated to the study of neutral and ionized molecules and nanoparticles under the low temperature and high vacuum conditions that are required to simulate various space environments such as diffuse interstellar clouds, circumstellar outflows and planetary atmospheres. COSmIC integrates a variety of state-of-the-art instruments that allow recreating simulated space conditions to generate, process and monitor cosmic analogs in the laboratory. The COSmIC experimental setup is composed of a Pulsed Discharge Nozzle (PDN) expansion, that generates a plasma in the stream of a free supersonic jet expansion, coupled to high-sensitivity, complementary in situ diagnostics: cavity ring down spectroscopy (CRDS) and laser induced fluorescence (LIF) systems for photonic detection, and Reflectron Time-Of-Flight Mass Spectrometer (ReTOF-MS) for mass detection. Recent results obtained using COSmIC will be highlighted. In particular, the progress that has been achieved in the domain of the diffuse interstellar bands (DIBs) and in monitoring, in the laboratory, the formation of circumstellar dust grains and planetary atmosphere aerosols from their gas-phase molecular precursors. Plans for future laboratory experiments on interstellar and planetary molecules and grains will also be addressed, as well as the implications of the studies underway for astronomical observations and past and future space mission data analysis.

  20. Insulin Fibrillation and Protein Design: Topological Resistance of Single-Chain Analogs to Thermal Degradation with Application to a Pump Reservoir

    PubMed Central

    Phillips, Nelson B.; Whittaker, Jonathan; Ismail-Beigi, Faramarz; Weiss, Michael A.

    2012-01-01

    Insulin is susceptible to thermal fibrillation, a misfolding process that leads to nonnative cross-b assembly analogous to pathological amyloid deposition. Pharmaceutical formulations are ordinarily protected from such degradation by sequestration of the susceptible monomer within native protein assemblies. With respect to the safety and efficacy of insulin pumps, however, this strategy imposes an intrinsic trade-off between pharmacokinetic goals (rapid absorption and clearance) and the requisite physical properties of a formulation (prolonged shelf life and stability within the reservoir). Available rapid-acting formulations are suboptimal in both respects; susceptibility to fibrillation is exacerbated even as absorption is delayed relative to the ideal specifications of a closed-loop system. To circumvent this molecular trade-off, we exploited structural models of insulin fibrils and amyloidogenic intermediates to define an alternative protective mechanism. Single-chain insulin (SCI) analogs were shown to be refractory to thermal fibrillation with maintenance of biological activity for more than 3 months under conditions that promote the rapid fibrillation and inactivation of insulin. The essential idea exploits an intrinsic incompatibility between SCI topology and the geometry of cross-b assembly. A peptide tether was thus interposed between the A- and B-chains whose length was (a) sufficiently long to provide the “play” needed for induced fit of the hormone on receptor binding and yet (b) sufficiently short to impose a topological barrier to fibrillation. Our findings suggest that ultrastable monomeric SCI analogs may be formulated without protective self-assembly and so permit simultaneous optimization of pharmacokinetics and reservoir life. PMID:22538136

  1. Insulin fibrillation and protein design: topological resistance of single-chain analogs to thermal degradation with application to a pump reservoir.

    PubMed

    Phillips, Nelson B; Whittaker, Jonathan; Ismail-Beigi, Faramarz; Weiss, Michael A

    2012-03-01

    Insulin is susceptible to thermal fibrillation, a misfolding process that leads to nonnative cross-β assembly analogous to pathological amyloid deposition. Pharmaceutical formulations are ordinarily protected from such degradation by sequestration of the susceptible monomer within native protein assemblies. With respect to the safety and efficacy of insulin pumps, however, this strategy imposes an intrinsic trade-off between pharmacokinetic goals (rapid absorption and clearance) and the requisite physical properties of a formulation (prolonged shelf life and stability within the reservoir). Available rapid-acting formulations are suboptimal in both respects; susceptibility to fibrillation is exacerbated even as absorption is delayed relative to the ideal specifications of a closed-loop system. To circumvent this molecular trade-off, we exploited structural models of insulin fibrils and amyloidogenic intermediates to define an alternative protective mechanism. Single-chain insulin (SCI) analogs were shown to be refractory to thermal fibrillation with maintenance of biological activity for more than 3 months under conditions that promote the rapid fibrillation and inactivation of insulin. The essential idea exploits an intrinsic incompatibility between SCI topology and the geometry of cross-β assembly. A peptide tether was thus interposed between the A- and B-chains whose length was (a) sufficiently long to provide the "play" needed for induced fit of the hormone on receptor binding and yet (b) sufficiently short to impose a topological barrier to fibrillation. Our findings suggest that ultrastable monomeric SCI analogs may be formulated without protective self-assembly and so permit simultaneous optimization of pharmacokinetics and reservoir life.

  2. 75 FR 54940 - Agency Information Collection (IC) Activities; Revision of an Approved IC; Accident Recordkeeping...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-09

    ... FMCSA has obtained more accurate data upon which to base calculation of the paperwork burden of this IC.... Improved FMCSA accident data provides a more accurate estimate of the total responses to this information...

  3. A closer look at IC 5201

    NASA Image and Video Library

    2016-12-12

    In 1900, astronomer Joseph Lunt made a discovery: Peering through a telescope at Cape Town Observatory, the British–South African scientist spotted this beautiful sight in the southern constellation of Grus (The Crane): a barred spiral galaxy now named IC 5201. Over a century later, the galaxy is still of interest to astronomers. For this image, the NASA/ESA Hubble Space Telescope used its Advanced Camera for Surveys (ACS) to produce a beautiful and intricate image of the galaxy. Hubble’s ACS can resolve individual stars within other galaxies, making it an invaluable tool to explore how various populations of stars have sprung to life, evolved, and died throughout the cosmos. IC 5201 sits over 40 million light-years away from us. As with two thirds of all the spirals we see in the Universe — including the Milky Way, the galaxy has a bar of stars slicing through its centre.

  4. Status of the ITER IC H and CD System

    SciTech Connect

    Lamalle, P. U.; Beaumont, B.; Gassmann, T.; Kazarian, F.; Arambhadiya, B.; Bora, D.; Jacquinot, J.; Mitteau, R.; Schueller, F. C.; Tanga, A.; Baruah, U.; Bhardwaj, A.; Kumar, R.; Mukherjee, A.; Singh, N. P.; Singh, R.; Goulding, R.; Rasmussen, D.; Swain, D.; Agarici, G.

    2009-11-26

    The ITER Ion Cyclotron Heating and Current Drive system will deliver 20 MW of radio frequency power to the plasma in quasi continuous operation during the different phases of the experimental programme. The system also has to perform conditioning of the tokamak first wall at low power between main plasma discharges. This broad range of requirements imposes a high flexibility and a high availability. The paper highlights the physics and design requirements on the IC system, the main features of its subsystems, the predicted performance, and the current procurement and installation schedule.

  5. Interstellar and Planetary Analogs in the Laboratory

    NASA Technical Reports Server (NTRS)

    Salama, Farid

    2013-01-01

    We present and discuss the unique capabilities of the laboratory facility, COSmIC, that was developed at NASA Ames to investigate the interaction of ionizing radiation (UV, charged particles) with molecular species (neutral molecules, radicals and ions) and carbonaceous grains in the Solar System and in the Interstellar Medium (ISM). COSmIC stands for Cosmic Simulation Chamber, a laboratory chamber where interstellar and planetary analogs are generated, processed and analyzed. It is composed of a pulsed discharge nozzle (PDN) expansion that generates a free jet supersonic expansion in a plasma cavity coupled to two ultrahigh-sensitivity, complementary in situ diagnostics: a cavity ring down spectroscopy (CRDS) system for photonic detection and a Reflectron time-of-flight mass spectrometer (ReTOF-MS) for mass detection. This setup allows the study of molecules, ions and solids under the low temperature and high vacuum conditions that are required to simulate some interstellar, circumstellar and planetary physical environments providing new fundamental insights on the molecular level into the processes that are critical to the chemistry in the ISM, circumstellar and planet forming regions, and on icy objects in the Solar System. Recent laboratory results that were obtained using COSmIC will be discussed, in particular the progress that have been achieved in monitoring in the laboratory the formation of solid particles from their gas-phase molecular precursors in environments as varied as circumstellar outflow and planetary atmospheres.

  6. The IC 342-Maffei 1 Group Revealed

    NASA Astrophysics Data System (ADS)

    McCall, M. L.; Buta, R.

    1996-12-01

    Deep wide-field CCD images of thirteen members of the IC 342-Maffei 1 Group in the Northern Milky Way have been acquired in the Johnson V and Cousins I photometric systems. The observations were obtained with the Kitt Peak Burrell-Schmidt telescope in Arizona during six nights in November 1995. Almost none of these galaxies was effectively studied in the past because of the heavy foreground extinction and significant foreground star contamination in the direction of the group. The tens of thousands of foreground stars included on the Schmidt images have been successfully subtracted using DAOPHOT, revealing the true extent and total brightness of most of the galaxies for the first time. In the absence of galactic extinction, Maffei 1, Maffei 2, and IC 342 would be among the five brightest galaxies in the northern sky, and both Maffei 1 and IC 342 would subtend angles as large as the full Moon. The results are critical for assessing the degree to which the group influenced the dynamical evolution of the Local Group. In this poster, we will present deep photographs, total magnitudes and color indices, luminosity profiles, and distance estimates for the member galaxies.

  7. Abundances in the Planetary Nebula IC 5217

    NASA Technical Reports Server (NTRS)

    Hyung, Siek; Aller, Lawrence H.; Feibelman, Walter A.; Lee, Woo-Baik; Fisher, Richard R. (Technical Monitor)

    2001-01-01

    High resolution optical wavelength spectroscopic data were secured in the optical wavelengths, 3700A - 10,050A, for the planetary nebula IC 5217 with the Hamilton Echelle Spectrograph at Lick Observatory. These optical spectra have been analyzed along with the near-UV and UV archive data. Diagnostic analyses indicate a nebular physical condition with electron temperature of about 10,700 K (from the [O III] lines) and the density of N(sub epsilon) = 5000/cm. Ionic concentrations have been derived with the representative diagnostics, and with the aid of a photoionization model construction, we derived the elemental abundances. Contrary to the previous studies found in the literature, He and C appear to be depleted compared to the average planetary nebula and to the Sun (and S marginally so), while the remaining elements appear to be close to the average value. IC 5217 may have evolved from an O-rich progenitor and the central star temperature of IC 5217 is likely to be 92,000 K.

  8. Molecular Hydrogen Fluorescence in IC 63

    NASA Technical Reports Server (NTRS)

    Andersson, B-G

    2005-01-01

    This grant has supported the acquisition, reduction and analysis of data targeting the structure and excitation of molecular hydrogen in the reflection nebula IC 63 and in particular the fluorescent emission seen in the UV. In addition to manpower for analyzing the FUSE data, the grant supported the (attempted) acquisition of supporting ground-based data. We proposed for and received observing time for two sets of ground based, data; narrow band imaging ([S II], [O III) at KPNO (July 2002; Observer: Burgh) and imaging spectro-photometry of several of the near-infrared rotation-vibration lines of H2 at the IRTF (October 2003; Observer: Andersson). Unfortunately, both of these runs were failures, primarily because of bad weather, and did not result in any useful data. We combined the FUSE observations with rocket borne observations of the star responsible for exciting the H2 fluorescence in IC 63: gamma Cas, and with archival HUT observations of IC 63, covering the long-wavelength part of the molecular hydrogen fluorescence.

  9. High Rate for Type IC Supernovae

    SciTech Connect

    Muller, R.A.; Marvin-Newberg, H.J.; Pennypacker, Carl R.; Perlmutter, S.; Sasseen, T.P.; Smith, C.K.

    1991-09-01

    Using an automated telescope we have detected 20 supernovae in carefully documented observations of nearby galaxies. The supernova rates for late spiral (Sbc, Sc, Scd, and Sd) galaxies, normalized to a blue luminosity of 10{sup 10} L{sub Bsun}, are 0.4 h{sup 2}, 1.6 h{sup 2}, and 1.1 h{sup 2} per 100 years for SNe type la, Ic, and II. The rate for type Ic supernovae is significantly higher than found in previous surveys. The rates are not corrected for detection inefficiencies, and do not take into account the indications that the Ic supernovae are fainter on the average than the previous estimates; therefore the true rates are probably higher. The rates are not strongly dependent on the galaxy inclination, in contradiction to previous compilations. If the Milky Way is a late spiral, then the rate of Galactic supernovae is greater than 1 per 30 {+-} 7 years, assuming h = 0.75. This high rate has encouraging consequences for future neutrino and gravitational wave observatories.

  10. Simulation of SEU transients in CMOS ICs

    SciTech Connect

    Kaul, N.; Bhuva, B.L.; Kerns, S.E. )

    1991-12-01

    This paper reports that available analytical models of the number of single-event-induced errors (SEU) in combinational logic systems are not easily applicable to real integrated circuits (ICs). An efficient computer simulation algorithm set, SITA, predicts the vulnerability of data stored in and processed by complex combinational logic circuits to SEU. SITA is described in detail to allow researchers to incorporate it into their error analysis packages. Required simulation algorithms are based on approximate closed-form equations modeling individual device behavior in CMOS logic units. Device-level simulation is used to estimate the probability that ion-device interactions produce erroneous signals capable of propagating to a latch (or n output node), and logic-level simulation to predict the spread of such erroneous, latched information through the IC. Simulation results are compared to those from SPICE for several circuit and logic configurations. SITA results are comparable to this established circuit-level code, and SITA can analyze circuits with state-of-the-art device densities (which SPICE cannot). At all IC complexity levels, SITAS offers several factors of 10 savings in simulation time over SPICE.

  11. Molecular Hydrogen Fluorescence in IC 63

    NASA Technical Reports Server (NTRS)

    Andersson, B-G

    2005-01-01

    This grant has supported the acquisition, reduction and analysis of data targeting the structure and excitation of molecular hydrogen in the reflection nebula IC 63 and in particular the fluorescent emission seen in the UV. In addition to manpower for analyzing the FUSE data, the grant supported the (attempted) acquisition of supporting ground-based data. We proposed for and received observing time for two sets of ground based, data; narrow band imaging ([S II], [O III) at KPNO (July 2002; Observer: Burgh) and imaging spectro-photometry of several of the near-infrared rotation-vibration lines of H2 at the IRTF (October 2003; Observer: Andersson). Unfortunately, both of these runs were failures, primarily because of bad weather, and did not result in any useful data. We combined the FUSE observations with rocket borne observations of the star responsible for exciting the H2 fluorescence in IC 63: gamma Cas, and with archival HUT observations of IC 63, covering the long-wavelength part of the molecular hydrogen fluorescence.

  12. Challenges in Using Analogies

    NASA Astrophysics Data System (ADS)

    Lin, Shih-Yin; Singh, Chandralekha

    2011-11-01

    Learning physics requires understanding the applicability of fundamental principles in a variety of contexts that share deep features.1-7 One way to help students learn physics is via analogical reasoning. Students can be taught to make an analogy between situations that are more familiar or easier to understand and another situation where the same physics principle is involved but that is more difficult to handle. Here, we examine introductory physics students' ability to use analogies in solving problems involving Newton's second law. Students enrolled in an algebra-based introductory physics course were given a solved problem involving tension in a rope and were then asked to solve another problem for which the physics is very similar but involved a frictional force. They were asked to point out the similarities between the two problems and then use the analogy to solve the friction problem.

  13. Fatty acid analogs

    DOEpatents

    Elmaleh, David R.; Livni, Eli

    1985-01-01

    In one aspect, a radioactively labeled analog of a fatty acid which is capable of being taken up by mammalian tissue and which exhibits an in vivo beta-oxidation rate below that with a corresponding radioactively labeled fatty acid.

  14. Design, synthesis and evaluation of a potent substrate analog inhibitor identified by scanning Ala/Phe mutagenesis, mimicking substrate co-evolution, against multidrug-resistant HIV-1 protease

    SciTech Connect

    Yedidi, Ravikiran S.; Muhuhi, Joseck M.; Liu, Zhigang; Bencze, Krisztina Z.; Koupparis, Kyriacos; O’Connor, Carrie E.; Kovari, Iulia A.; Spaller, Mark R.; Kovari, Ladislau C.

    2013-09-06

    Highlights: •Inhibitors against MDR HIV-1 protease were designed, synthesized and evaluated. •Lead peptide (6a) showed potent inhibition (IC{sub 50}: 4.4 nM) of MDR HIV-1 protease. •(6a) Showed favorable binding isotherms against NL4-3 and MDR proteases. •(6a) Induced perturbations in the {sup 15}N-HSQC spectrum of MDR HIV-1 protease. •Molecular modeling suggested that (6a) may induce total flap closure inMDR protease. -- Abstract: Multidrug-resistant (MDR) clinical isolate-769, human immunodeficiency virus type-1 (HIV-1) protease (PDB ID: (1TW7)), was shown to exhibit wide-open flaps and an expanded active site cavity, causing loss of contacts with protease inhibitors. In the current study, the expanded active site cavity of MDR769 HIV-1 protease was screened with a series of peptide-inhibitors that were designed to mimic the natural substrate cleavage site, capsid/p2. Scanning Ala/Phe chemical mutagenesis approach was incorporated into the design of the peptide series to mimic the substrate co-evolution. Among the peptides synthesized and evaluated, a lead peptide (6a) with potent activity (IC{sub 50}: 4.4 nM) was identified against the MDR769 HIV-1 protease. Isothermal titration calorimetry data showed favorable binding profile for 6aagainst both wild type and MDR769 HIV-1 protease variants. Nuclear magnetic resonance spectrum of {sup 15}N-labeled MDR769 HIV-1 protease in complex with 6a showed some major perturbations in chemical shift, supporting the peptide induced conformational changes in protease. Modeling analysis revealed multiple contacts between 6a and MDR769 HIV-1 protease. The lead peptide-inhibitor, 6a, with high potency and good binding profile can be used as the basis for developing potent small molecule inhibitors against MDR variants of HIV.

  15. DETECTION AND QUANTIFICATION OF THIO-ARSENOSUGAR IN MARINE MOLLUSKS BY IC-ICP-MS WITH AN EMPHASIS ON THE INTERACTION OF ARSENOSUGARS WITH SULFIDE AS A FUNCTION OF PH

    EPA Science Inventory

    The sulfar analog of As(328)(2,3-dihydroxypropyl-5-deoxy-5-dimethylarsinoyl-ß-D-riboside), abbreviated (As(328-S), was detected and quantified in five species of marine shellfish using IC-ICP-MS with structural verification via IC-ESI-MS/MS. The CAD spectra produced from the par...

  16. DETECTION AND QUANTIFICATION OF THIO-ARSENOSUGAR IN MARINE MOLLUSKS BY IC-ICP-MS WITH AN EMPHASIS ON THE INTERACTION OF ARSENOSUGARS WITH SULFIDE AS A FUNCTION OF PH

    EPA Science Inventory

    The sulfar analog of As(328)(2,3-dihydroxypropyl-5-deoxy-5-dimethylarsinoyl-ß-D-riboside), abbreviated (As(328-S), was detected and quantified in five species of marine shellfish using IC-ICP-MS with structural verification via IC-ESI-MS/MS. The CAD spectra produced from the par...

  17. FGF growth factor analogs

    DOEpatents

    Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

    2012-07-24

    The present invention provides a fibroblast growth factor heparin-binding analog of the formula: ##STR00001## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, X, Y and Z are as defined, pharmaceutical compositions, coating compositions and medical devices including the fibroblast growth factor heparin-binding analog of the foregoing formula, and methods and uses thereof.

  18. Analog Nonvolatile Computer Memory Circuits

    NASA Technical Reports Server (NTRS)

    MacLeod, Todd

    2007-01-01

    In nonvolatile random-access memory (RAM) circuits of a proposed type, digital data would be stored in analog form in ferroelectric field-effect transistors (FFETs). This type of memory circuit would offer advantages over prior volatile and nonvolatile types: In a conventional complementary metal oxide/semiconductor static RAM, six transistors must be used to store one bit, and storage is volatile in that data are lost when power is turned off. In a conventional dynamic RAM, three transistors must be used to store one bit, and the stored bit must be refreshed every few milliseconds. In contrast, in a RAM according to the proposal, data would be retained when power was turned off, each memory cell would contain only two FFETs, and the cell could store multiple bits (the exact number of bits depending on the specific design). Conventional flash memory circuits afford nonvolatile storage, but they operate at reading and writing times of the order of thousands of conventional computer memory reading and writing times and, hence, are suitable for use only as off-line storage devices. In addition, flash memories cease to function after limited numbers of writing cycles. The proposed memory circuits would not be subject to either of these limitations. Prior developmental nonvolatile ferroelectric memories are limited to one bit per cell, whereas, as stated above, the proposed memories would not be so limited. The design of a memory circuit according to the proposal must reflect the fact that FFET storage is only partly nonvolatile, in that the signal stored in an FFET decays gradually over time. (Retention times of some advanced FFETs exceed ten years.) Instead of storing a single bit of data as either a positively or negatively saturated state in a ferroelectric device, each memory cell according to the proposal would store two values. The two FFETs in each cell would be denoted the storage FFET and the control FFET. The storage FFET would store an analog signal value

  19. Special IC's in digital switching - An overview

    NASA Astrophysics Data System (ADS)

    Rosenbaum, S. D.

    1981-08-01

    This paper traces the influence of special-purpose integrated and LSI circuits in digital switching systems. The existence of custom digital chips, codecs and filters, and high- and low-voltage analog crosspoint arrays is related to the choice between alternative architectures. Recent trends toward replacing mature components such as transformers by subscriber line interface circuits (SLIC's) are outlined

  20. Electrical Circuits and Water Analogies

    ERIC Educational Resources Information Center

    Smith, Frederick A.; Wilson, Jerry D.

    1974-01-01

    Briefly describes water analogies for electrical circuits and presents plans for the construction of apparatus to demonstrate these analogies. Demonstrations include series circuits, parallel circuits, and capacitors. (GS)

  1. Electrical Circuits and Water Analogies

    ERIC Educational Resources Information Center

    Smith, Frederick A.; Wilson, Jerry D.

    1974-01-01

    Briefly describes water analogies for electrical circuits and presents plans for the construction of apparatus to demonstrate these analogies. Demonstrations include series circuits, parallel circuits, and capacitors. (GS)

  2. Leishmanicidal Effect of Synthetic trans-Resveratrol Analogs

    PubMed Central

    Soares, Deivid Costa; Saraiva, Elvira Maria

    2015-01-01

    Background Stilbene-based compounds show antitumoral, antioxidant, antihistaminic, anti-inflammatory and antimicrobial activities. Here, we evaluated the effect of the trans-resveratrol analogs, pterostilbene, piceatannol, polydatin and oxyresveratrol, against Leishmania amazonensis. Methodology/Principal Findings Our results demonstrated a low murine macrophage cytotoxicity of all four analogs. Moreover, pterostilbene, piceatannol, polydatin and oxyresveratrol showed an anti-L. amazonensis activity with IC50 values of 18 μM, 65 μM, 95 μM and 65 μM for promastigotes, respectively. For intracellular amastigotes, the IC50 values of the analogs were 33.2 μM, 45 μM, 29 μM and 30.5 μM, respectively. Among the analogs assayed only piceatannol altered the cell cycle of the parasite, increasing 5-fold the cells in the Sub-G0 phase and decreasing 1.7-fold the cells in the G0-G1 phase. Piceatannol also changed the parasite mitochondrial membrane potential (ΔΨm) and increased the number of annexin-V positive promastigotes, which suggests incidental death. Conclusion/Significance Among the analogs tested, piceatannol, which is a metabolite of resveratrol, was the more promising candidate for future studies regarding treatment of leishmaniasis. PMID:26517558

  3. Chip Design Process Optimization Based on Design Quality Assessment

    NASA Astrophysics Data System (ADS)

    Häusler, Stefan; Blaschke, Jana; Sebeke, Christian; Rosenstiel, Wolfgang; Hahn, Axel

    2010-06-01

    Nowadays, the managing of product development projects is increasingly challenging. Especially the IC design of ASICs with both analog and digital components (mixed-signal design) is becoming more and more complex, while the time-to-market window narrows at the same time. Still, high quality standards must be fulfilled. Projects and their status are becoming less transparent due to this complexity. This makes the planning and execution of projects rather difficult. Therefore, there is a need for efficient project control. A main challenge is the objective evaluation of the current development status. Are all requirements successfully verified? Are all intermediate goals achieved? Companies often develop special solutions that are not reusable in other projects. This makes the quality measurement process itself less efficient and produces too much overhead. The method proposed in this paper is a contribution to solve these issues. It is applied at a German design house for analog mixed-signal IC design. This paper presents the results of a case study and introduces an optimized project scheduling on the basis of quality assessment results.

  4. Creative synthesis of novel vitamin D analogs for health and disease.

    PubMed

    Kittaka, Atsushi; Saito, Nozomi; Honzawa, Shinobu; Takenouchi, Kazuya; Ishizuka, Seiichi; Chen, Tai C; Peleg, Sara; Kato, Shigeaki; Arai, Midori A

    2007-03-01

    We report new analogs of 1alpha,25-dihydroxyvitamin D(3) (1) in three categories. First, design and synthesis of ligands for a mutant vitamin D receptor (VDR)(Arg274Leu), which possess proper functional groups at both C1alpha and C2alpha positions of 1 to study the biological activity of the mutant VDR. Among our synthetic analogs, 1alpha-methyl-2alpha-(3-hydroxypropyl)-25-hydroxyvitamin D(3) (8) showed 7.3-fold greater transcriptional activity for the VDR(Arg274Leu) than that of 1. Next, we examined the antiproliferative activity of 2-substituted 19-norvitamin D(3) analogs on an immortalized normal prostate cell line, PZ-HPV-7, and we found MART 10 (14) showed the activity even at very low concentration of 10(-10) to 10(-11)M. We also synthesized 25-hydroxy-19-norvitamin D(3) (13) using Julia-type olefination to connect between the C5 and C6 positions, effectively, to test it as a prohormone type agent for antiprostate diseases. Synthesized compound 13 showed potent antiproliferative activity in PZ-HPV-7, which has high 1alpha-hydroxylase activity. Finally, we describe design and synthesis of a new TEI-9647 analog, 2alpha-(3-hydroxypropoxy)-24-propyl-25-dehydro-1alpha-hydroxyvitamin D(3)-26,23-lactone (17), which showed the strongest VDR antagonism. Its IC(50) value is 7.4pM to inhibit differentiation of HL-60 cells induced by 10nM of 1.

  5. Design of a case management model for people with chronic disease (Heart Failure and COPD). Phase I: modeling and identification of the main components of the intervention through their actors: patients and professionals (DELTA-icE-PRO Study)

    PubMed Central

    2010-01-01

    Background Chronic diseases account for nearly 60% of deaths around the world. The extent of this silent epidemic has not met determined responses in governments, policies or professionals in order to transform old Health Care Systems, configured for acute diseases. There is a large list of research about alternative models for people with chronic conditions, many of them with an advanced practice nurse as a key provider, as case management. But some methodological concerns raise, above all, the design of the intervention (intensity, frequency, components, etc). Methods/Design Objectives: General: To develop the first and second phases (theorization and modeling) for designing a multifaceted case-management intervention in people with chronic conditions (COPD and heart failure) and their caregivers. Specific aims: 1) To identify key events in people living with chronic disease and their relation with the Health Care System, from their point of view. 2) To know the coping mechanisms developed by patients and their caregivers along the story with the disease. 3) To know the information processing and its utilization in their interactions with health care providers. 4) To detect potential unmet needs and the ways deployed by patients and their caregivers to resolve them. 5) To obtain a description from patients and caregivers, about their itineraries along the Health Care System, in terms of continuity, accessibility and comprehensiveness of care. 6) To build up a list of promising case-management interventions in patients with Heart Failure and COPD with this information in order to frame it into theoretical models for its reproducibility and conceptualization. 7) To undergo this list to expert judgment to assess its feasibility and pertinence in the Andalusian Health Care. Design: Qualitative research with two phases: For the first five objectives, a qualitative technique with biographic stories will be developed and, for the remaining objectives, an expert

  6. Design, synthesis, and biological evaluation of pirenzepine analogs bearing a 1,2-cyclohexanediamine and perhydroquinoxaline units in exchange for the piperazine ring as antimuscarinics.

    PubMed

    Minarini, Anna; Marucci, Gabriella; Bellucci, Cristina; Giorgi, Gianluca; Tumiatti, Vincenzo; Bolognesi, Maria Laura; Matera, Riccardo; Rosini, Michela; Melchiorre, Carlo

    2008-08-01

    Pirenzepine (2) is one of the most selective muscarinic M(1) versus M(2) receptor antagonists known. A series of 2 analogs, in which the piperazyl moiety was replaced by a cis- and trans-cyclohexane-1,2-diamine (3-6) or a trans- and cis-perhydroquinoxaline rings (7 and 8) were prepared, with the aim to investigate the role of the piperazine ring of 2 in the interaction with the muscarinic receptors. The structural change leading to compounds 3-6 abolished in binding assays the muscarinic M(1)/M(2) selectivity of 2, due to an increased M(2) affinity. Rather, compounds 3-6 displayed a reversed selectivity showing more affinity at the muscarinic M(2) receptor than at all the other subtypes tested.

  7. Comparative evaluation of pressure generated on a simulated maxillary oral analog by impression materials in custom trays of different spacer designs: An in vitro study

    PubMed Central

    Chopra, Sakshi; Gupta, Narendra Kumar; Tandan, Amrit; Dwivedi, Ravi; Gupta, Swati; Agarwal, Garima

    2016-01-01

    Introduction: Literature reveals that masticatory load on denture bearing tissues through complete dentures should be maximum on primary stress bearing areas and least on relief area in accordance with the histology of underlying tissues. A study to validate the existing beliefs was planned to compare the pressure on mucosa using selective pressure technique and minimal pressure technique, with the incorporation of two different impression materials utilizing the pressure sensors during secondary impression procedure. Materials and Methods: The study was performed using a maxillary analog. Three pressure sensors were imbedded in the oral analog, one in the mid palatine area and the other two in the right and left ridge crest. Custom trays of two different configurations were fabricated. The two impression materials tested were light body and zinc oxide eugenol. A total of 40 impressions were made. A constant weight of 1 kg was placed, and the pressure was recorded as initial and end pressures. Results: A significant difference in the pressure produced using different impression materials was found (P < 0.001). Light body vinyl polysiloxane produced significantly lesser pressure than zinc oxide eugenol impression materials. The presence of relief did affect the magnitude of pressure at various locations. Conclusion: All impression materials produced pressure during maxillary edentulous impression making. Tray modification is an important factor in changing the amount of pressure produced. The impression materials used also had a significant role to play on the pressures acting on the tissues during impression procedure. Clinical Implication: Light body VPS impression material may be recommended to achieve minimal pressure on the denture bearing tissues in both selective as well as minimal pressure techniques. PMID:27041902

  8. Comparative evaluation of pressure generated on a simulated maxillary oral analog by impression materials in custom trays of different spacer designs: An in vitro study.

    PubMed

    Chopra, Sakshi; Gupta, Narendra Kumar; Tandan, Amrit; Dwivedi, Ravi; Gupta, Swati; Agarwal, Garima

    2016-01-01

    Literature reveals that masticatory load on denture bearing tissues through complete dentures should be maximum on primary stress bearing areas and least on relief area in accordance with the histology of underlying tissues. A study to validate the existing beliefs was planned to compare the pressure on mucosa using selective pressure technique and minimal pressure technique, with the incorporation of two different impression materials utilizing the pressure sensors during secondary impression procedure. The study was performed using a maxillary analog. Three pressure sensors were imbedded in the oral analog, one in the mid palatine area and the other two in the right and left ridge crest. Custom trays of two different configurations were fabricated. The two impression materials tested were light body and zinc oxide eugenol. A total of 40 impressions were made. A constant weight of 1 kg was placed, and the pressure was recorded as initial and end pressures. A significant difference in the pressure produced using different impression materials was found (P < 0.001). Light body vinyl polysiloxane produced significantly lesser pressure than zinc oxide eugenol impression materials. The presence of relief did affect the magnitude of pressure at various locations. All impression materials produced pressure during maxillary edentulous impression making. Tray modification is an important factor in changing the amount of pressure produced. The impression materials used also had a significant role to play on the pressures acting on the tissues during impression procedure. Light body VPS impression material may be recommended to achieve minimal pressure on the denture bearing tissues in both selective as well as minimal pressure techniques.

  9. Design of a case management model for people with chronic disease (Heart Failure and COPD). Phase I: modeling and identification of the main components of the intervention through their actors: patients and professionals (DELTA-icE-PRO Study).

    PubMed

    Morales-Asencio, Jose M; Martin-Santos, Francisco J; Morilla-Herrera, Juan C; Fernández-Gallego, Magdalena Cuevas; Celdrán-Mañas, Miriam; Navarro-Moya, Francisco J; Rodríguez-Salvador, Maria M; Muñoz-Ronda, Francisco J; Gonzalo-Jiménez, Elena; Carrasco, Almudena Millán

    2010-12-02

    Chronic diseases account for nearly 60% of deaths around the world. The extent of this silent epidemic has not met determined responses in governments, policies or professionals in order to transform old Health Care Systems, configured for acute diseases. There is a large list of research about alternative models for people with chronic conditions, many of them with an advanced practice nurse as a key provider, as case management. But some methodological concerns raise, above all, the design of the intervention (intensity, frequency, components, etc). General: To develop the first and second phases (theorization and modeling) for designing a multifaceted case-management intervention in people with chronic conditions (COPD and heart failure) and their caregivers. 1) To identify key events in people living with chronic disease and their relation with the Health Care System, from their point of view. 2) To know the coping mechanisms developed by patients and their caregivers along the story with the disease. 3) To know the information processing and its utilization in their interactions with health care providers. 4) To detect potential unmet needs and the ways deployed by patients and their caregivers to resolve them. 5) To obtain a description from patients and caregivers, about their itineraries along the Health Care System, in terms of continuity, accessibility and comprehensiveness of care. 6) To build up a list of promising case-management interventions in patients with Heart Failure and COPD with this information in order to frame it into theoretical models for its reproducibility and conceptualization. 7) To undergo this list to expert judgment to assess its feasibility and pertinence in the Andalusian Health Care. Qualitative research with two phases: For the first five objectives, a qualitative technique with biographic stories will be developed and, for the remaining objectives, an expert consensus through Delphi technique, on the possible interventions

  10. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1962-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. After a 6 month delay in construction due to size reconfiguration of the Saturn booster, the site was revisited for modifications. The original foundation walls built in the prior year had to be torn down and re-poured to accommodate the larger booster. The demolition can be seen in this photograph taken on May 21, 1962.

  11. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1962-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. After a six month delay in construction due to size reconfiguration of the Saturn booster, the site was revisited for modifications in March 1962. The original foundation walls built in the prior year were torn down and re-poured to accommodate the larger boosters. This photo depicts that modification progress as of June 13,1962.

  12. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1961-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photo shows the construction progress of the test stand as of August 14, 1961. Water gushing in from the disturbance of a natural spring contributed to constant water problems during the construction process. It was necessary to pump water from the site on a daily basis and is still pumped from the site today. The equipment is partially submerged in the water emerging from the spring.

  13. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1961-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photo, taken September 5, 1961, shows the construction of forms which became the concrete foundation for the massive stand. The lower right hand corner reveals a pump used for extracting water emerging from a disturbed natural spring that occurred during excavation of the site. The pumping became a daily ritual and the site is still pumped today.

  14. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1961-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. This photo, taken September 5, 1961, shows the construction of forms which became the concrete foundation for the massive stand. The lower right hand corner reveals a pump used for extracting water emerging from a disturbed natural spring that occurred during excavation of the site. The pumping became a daily ritual and the site is still pumped today.

  15. Construction Progress of S-IC Test Stand Pump House

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. In addition to the stand itself, related facilities were constructed during this time. Built to the northeast east was a newly constructed Pump House. Its function was to provide water to the stand to prevent melting damage during testing. The water was sprayed through small holes in the stand's 1900 ton flame deflector at the rate of 320,000 gallons per minute. This photograph of the Pump House area was taken August 13, 1963. The massive round water storage tanks can be seen to the left of

  16. Construction Progress of S-IC Test Stand Pump House

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. In addition to the stand itself, related facilities were constructed during this time. Built to the northeast east was a newly constructed Pump House. Its function was to provide water to the stand to prevent melting damage during testing. The water was sprayed through small holes in the stand's 1900 ton flame deflector at the rate of 320,000 gallons per minute. This photograph of the Pump House area was taken August 13, 1963. The massive round water storage tanks can be seen to the left of

  17. Construction Progress S-IC Test Stand Block House Interior

    NASA Technical Reports Server (NTRS)

    1963-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. In addition to the stand itself, related facilities were constructed during this time. Built directly east of the test stand was the Block House, which served as the control center for the test stand. The two were connected by a narrow access tunnel which housed the cables for the controls. This photograph, taken August 12, 1963, offers a view of the Block House interior.

  18. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1962-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. After a six month delay in construction due to size reconfiguration of the Saturn booster, the site was revisited for modifications in March 1962. The original foundation walls built in the prior year were torn down and re-poured to accommodate the larger boosters. This photo depicts that modification progress as of June 13,1962.

  19. Construction Progress of the S-IC Test Stand

    NASA Technical Reports Server (NTRS)

    1962-01-01

    At its founding, the Marshall Space Flight Center (MSFC) inherited the Army's Jupiter and Redstone test stands, but much larger facilities were needed for the giant stages of the Saturn V. From 1960 to 1964, the existing stands were remodeled and a sizable new test area was developed. The new comprehensive test complex for propulsion and structural dynamics was unique within the nation and the free world, and they remain so today because they were constructed with foresight to meet the future as well as on going needs. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. The S-IC static test stand was designed to develop and test the 138-ft long and 33-ft diameter Saturn V S-IC first stage, or booster stage, weighing in at 280,000 pounds. Required to hold down the brute force of a 7,500,000-pound thrust produced by 5 F-1 engines, the S-IC static test stand was designed and constructed with the strength of hundreds of tons of steel and 12,000,000 pounds of cement, planted down to bedrock 40 feet below ground level. The foundation walls, constructed with concrete and steel, are 4 feet thick. The base structure consists of four towers with 40-foot-thick walls extending upward 144 feet above ground level. The structure was topped by a crane with a 135-foot boom. With the boom in the upright position, the stand was given an overall height of 405 feet, placing it among the highest structures in Alabama at the time. After a 6 month delay in construction due to size reconfiguration of the Saturn booster, the site was revisited for modifications. The original foundation walls built in the prior year had to be torn down and re-poured to accommodate the larger booster. The demolition can be seen in this photograph taken on May 21, 1962.

  20. Finding Young Stars in IC417

    NASA Astrophysics Data System (ADS)

    Odden, Caroline; Rebull, Luisa M.; Sanchez, Richard; Hall, Garrison; Dear, AnnaMaria; Hengel, Cassie; LaRocca, Mia; Lin, Samantha; Nix, Sabine; Sweckard, Teaghan; Wilhelm, Katie

    2016-01-01

    IC 417 is a young cluster in the constellation Auriga, towards the Galactic anti-center in the Perseus arm, at a distance of ~2.3 kpc. Previous studies suggested that there are young stars in this region; Camargo et al. (2012) identified several few-Myr-old clusters in this region from 2MASS clustering, and Jose et al. (2008) identified H-alpha excess sources. Since stars form from clouds of interstellar dust and gas, a signature of star formation is excess infrared (IR) emission, which is interpreted as evidence for circumstellar dust around young stars. We identified new candidate young stellar objects (YSOs) in IC 417 by incorporating near- and mid-infrared observations from the Wide-field Infrared Survey Explorer (WISE) and the Two Micron All-Sky Survey (2MASS). Infrared excess sources were identified by using a series of color cuts in various 2MASS/WISE color-magnitude and color-color diagrams following Koenig & Leisawitz (2014). We also assembled a list of OB and H-alpha stars from the literature, including those from Jose et al. (2008), and H-alpha bright stars from the IPHAS survey (Witham et al. 2008). Starting with this compiled list of approximately 200 interesting objects in the region, we then set about checking their reliability in three ways. We inspected the POSS, 2MASS, and WISE images of the sources. We assembled and inspected spectral energy distributions (SEDs) from archival data ranging from wavelengths of 0.7 to 22 um. Finally, we created and inspected color-color and color-magnitude diagrams. We find enough new YSO candidates to more than double the number yet identified in the IC 417 region. This research was made possible through the NASA/IPAC Teacher Archive Research Program (NITARP) and was funded by NASA Astrophysics Data Program.