Modulator

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Christopher J. Langmead - One of the best experts on this subject based on the ideXlab platform.

  • as a Screening Paradigm Screening for Positive Allosteric Modulators: Assessment of Modulator Concentration-Response Curves
    2013
    Co-Authors: Christopher J. Langmead
    Abstract:

    Targeting allosteric binding sites represents a powerful mechanism for selectively modulating receptor function. The advent offunctional assays as the screening method of choice is leading to an increase in the number of allosteric Modulators identified.These include positive allosteric Modulators that can increase the affinity of the orthosteric agonist and potentiate the evokedresponse. A common method for screening for positive allosteric Modulators is to examine a concentration-response (C/R) curveto the putative Modulator in the presence of a single, low concentration of agonist. The study reported here has used data sim-ulations for positive allosteric Modulators according to the allosteric ternary complex model to generate Modulator C/R curves.The results are then compared to the mechanistic parameters used to simulate the data. It is clear from the simulations that thepotency of a positive Modulator C/R curve in a screening assay is the product of both its affinity and positive cooperativity.However, it is often difficult to tell which parameter dominates the response; not knowing the actual affinity or cooperativity ofa ligand may have consequences for receptor selectivity. Further modeling demonstrates that the use and choice of single ago-nist concentration, as well as changes in the agonist curve Hill slope, can have significant effects on the Modulator C/R curve.Finally, the quantitative relationship between Modulator C/R curves and the allosteric ternary complex model is explored. Thesesimulations emphasize the importance of careful interpretation of screening data and of conducting full mechanism of actionstudies for positive allosteric Modulators. (

  • Screening for Positive Allosteric Modulators: Assessment of Modulator Concentration-Response Curves as a Screening Paradigm
    Journal of biomolecular screening, 2007
    Co-Authors: Christopher J. Langmead
    Abstract:

    Targeting allosteric binding sites represents a powerful mechanism for selectively modulating receptor function. The advent of functional assays as the screening method of choice is leading to an increase in the number of allosteric Modulators identified. These include positive allosteric Modulators that can increase the affinity of the orthosteric agonist and potentiate the evoked response. A common method for screening for positive allosteric Modulators is to examine a concentration-response (C/R) curve to the putative Modulator in the presence of a single, low concentration of agonist. The study reported here has used data simulations for positive allosteric Modulators according to the allosteric ternary complex model to generate Modulator C/R curves. The results are then compared to the mechanistic parameters used to simulate the data. It is clear from the simulations that the potency of a positive Modulator C/R curve in a screening assay is the product of both its affinity and positive cooperativity. However, it is often difficult to tell which parameter dominates the response; not knowing the actual affinity or cooperativity of a ligand may have consequences for receptor selectivity. Further modeling demonstrates that the use and choice of single agonist concentration, as well as changes in the agonist curve Hill slope, can have significant effects on the Modulator C/R curve. Finally, the quantitative relationship between Modulator C/R curves and the allosteric ternary complex model is explored. These simulations emphasize the importance of careful interpretation of screening data and of conducting full mechanism of action studies for positive allosteric Modulators. (Journal of Biomolecular Screening 2007:668-676)

  • Screening for Positive Allosteric Modulators: Assessment of Modulator Concentration-Response Curves as a Screening Paradigm
    Journal of biomolecular screening, 2007
    Co-Authors: Christopher J. Langmead
    Abstract:

    Targeting allosteric binding sites represents a powerful mechanism for selectively modulating receptor function. The advent of functional assays as the screening method of choice is leading to an increase in the number of allosteric Modulators identified. These include positive allosteric Modulators that can increase the affinity of the orthosteric agonist and potentiate the evoked response. A common method for screening for positive allosteric Modulators is to examine a concentration-response (C/R) curve to the putative Modulator in the presence of a single, low concentration of agonist. The study reported here has used data simulations for positive allosteric Modulators according to the allosteric ternary complex model to generate Modulator C/R curves. The results are then compared to the mechanistic parameters used to simulate the data. It is clear from the simulations that the potency of a positive Modulator C/R curve in a screening assay is the product of both its affinity and positive cooperativity. However, it is often difficult to tell which parameter dominates the response; not knowing the actual affinity or cooperativity of a ligand may have consequences for receptor selectivity. Further modeling demonstrates that the use and choice of single agonist concentration, as well as changes in the agonist curve Hill slope, can have significant effects on the Modulator C/R curve. Finally, the quantitative relationship between Modulator C/R curves and the allosteric ternary complex model is explored. These simulations emphasize the importance of careful interpretation of screening data and of conducting full mechanism of action studies for positive allosteric Modulators.

Bo Zhang - One of the best experts on this subject based on the ideXlab platform.

Gunhee Han - One of the best experts on this subject based on the ideXlab platform.

  • Low Voltage, low power, inverter-based switched-capacitor delta-sigma Modulator
    IEEE Journal of Solid-State Circuits, 2009
    Co-Authors: Youngcheol Chae, Gunhee Han
    Abstract:

    An operational transconductance amplifier (OTA) is a major building block and consumes most of the power in switched-capacitor (SC) circuits, but it is difficult to design low-voltage OTAs in scaled CMOS technologies. Instead of using an OTA, this paper proposes an inverter-based SC circuit and its application to low-voltage, low-power delta-sigma (DeltaSigma) Modulators. Detailed analysis and design optimizations are also provided. Three inverter-based Delta Sigma Modulators are implemented for an implantable pacemaker, a CMOS image sensor, and an audio codec. The Modulator-I for an implantable pacemaker achieves 65-dB peak-SNDR for 120-Hz bandwidth consuming 0.73 muW with 1.5 V supply. The Modulator-II for a CMOS image sensor implemented with 320-channel parallel ADC architecture achieves 63-dB peak-SNDR for 8-kHz bandwidth consuming 5.6 muW for each channel with 1.2-V supply. The Modulator-III for an audio codec achieves 81-dB peak-SNDR with 20-kHz bandwidth consuming 36 muW with 0.7-V supply. The prototype Delta Sigma Modulators achieved high power efficiency maintaining sufficient performances for practical applications.

Adel S. Sedra - One of the best experts on this subject based on the ideXlab platform.

  • transfer function design for spl delta spl sigma converters
    International Symposium on Circuits and Systems, 1994
    Co-Authors: S. Jantzi, C. Ouslis, Adel S. Sedra
    Abstract:

    A methodology is presented for the design of noise and signal transfer functions for delta-sigma Modulators. A computerised optimiser is used to produce maximal noise-shaping, while meeting those constraints necessary to realise a usable Modulator. The design of higher-order Modulators is possible, as is the design of unique noise-shaping functions such as for bandpass Modulators, complex Modulators, or Modulators with psychoacoustically-shaped in-band noise. Optimisation of the transfer function from Modulator input to output is also possible if special conditioning of the input signal is desired. >

  • Transfer function design for /spl Delta//spl Sigma/ converters
    Proceedings of IEEE International Symposium on Circuits and Systems - ISCAS '94, 1
    Co-Authors: S. Jantzi, C. Ouslis, Adel S. Sedra
    Abstract:

    A methodology is presented for the design of noise and signal transfer functions for delta-sigma Modulators. A computerised optimiser is used to produce maximal noise-shaping, while meeting those constraints necessary to realise a usable Modulator. The design of higher-order Modulators is possible, as is the design of unique noise-shaping functions such as for bandpass Modulators, complex Modulators, or Modulators with psychoacoustically-shaped in-band noise. Optimisation of the transfer function from Modulator input to output is also possible if special conditioning of the input signal is desired. >

John E. Bowers - One of the best experts on this subject based on the ideXlab platform.