Core Circuit Research Articles

Sac7 and Rho1 regulate the white-to-opaque switching in Candida albicans

Candida albicans cells homozygous at the mating-type locus stochastically undergo the white-to-opaque switching to become mating-competent. This switching is regulated by a core circuit of transcription factors organized through interlocking feedback loops around the master regulator Wor1. Although a range of distinct environmental cues is known to induce the switching, the pathways linking the external stimuli to the central control mechanism remains largely unknown. By screening a C. albicans haploid gene-deletion library, we found that SAC7 encoding a GTPase-activating protein of Rho1 is required for the white-to-opaque switching. We demonstrate that Sac7 physically associates with Rho1-GTP and the constitutively active Rho1G18V mutant impairs the white-to-opaque switching while the inactive Rho1D124A mutant promotes it. Overexpressing WOR1 in both sac7Δ/Δ and rho1G18V cells suppresses the switching defect, indicating that the Sac7/Rho1 module acts upstream of Wor1. Furthermore, we provide evidence that Sac7/Rho1 functions in a pathway independent of the Ras/cAMP pathway which has previously been positioned upstream of Wor1. Taken together, we have discovered new regulators and a signaling pathway that regulate the white-to-opaque switching in the most prevalent human fungal pathogen C. albicans.

A V-Band Doherty Power Amplifier Based on Voltage Combination and Balance Compensation Marchand Balun

This paper presents a $V$ -band Doherty power amplifier (PA) which is implemented in a standard 65-nm CMOS technology. The voltage combination technique is used to realize the millimeter-wave Doherty PA without the $\lambda $ /4 transmission lines. A Marchand balun with balance compensation is designed to combine the output power with reduced power loss. Moreover, a nonlinear driver is used to drive the peaking amplifier to enhance the output power and the turn-on speed of it. The power-added efficiency (PAE) of this PA at the 6-dB power back-off point is 8.7% and the peak PAE reaches 16.8%. The small signal power gain is 18 dB, and the maximum output power is 14.9 dBm. The core circuit only costs 0.195 mm2 chip area as no $\lambda $ /4 transmission lines.

Optimization Design and Development of Sensing Coil and Analog Signal Conditioning Electronics for Fluxgate Magnetometer Sensor

The design of fluxgate magnetometers is typically a nonlinear multi-objective optimization problem. Different objectives often conflict with each other, and sometimes an optimal Fluxgate Magnetometer Sensor (FMS) performance is difficult to achieve. The sensitivity of the sensor decreases with an increase of noise level while trying to reduce the sensor dimension. Hence, there is need for a systematic optimization approach for FMS design to find its optimum performance. The combined modified multi-objective Firefly Optimization Algorithm (FOA) and systematic optimization approach is suggested to improve FMS’s design in this research by simultaneously optimizing the sensitivity and noise of a FMS while the sensor core, pick-up coil, and detection circuit are minimized. The developed model allowed improved sensitivity of 86.65%, reduction of noise level by 59.97% while still keeping the sensor size small by 14.29%. Keywords: Fluxgate magnetometer sensor, noise, sensitivity, firefly optimization algorithm. DOI : 10.7176/ISDE/10-4-03 Publication date :May 31 st 2019

A 1.2 GSps, 8 bit RF DAC for multi-Nyquist applications in GaAs technology

High-speed digital-to-analog converter (DAC) is key component in instrument and automatic test equipment, radar and ultra-wideband (UWB) systems. In this paper, a two-channel 1.2 GSps, 8 bit RF DAC for Multi-Nyquist applications in 1 µm GaAs Technology is presented. Combining mode select circuit with synchronous latch simplifies design of the current source and layout of DAC core circuit. Measurement results demonstrate that the Differential Nonlinearity (DNL) is within ±0.15 LSB, and the Integral Nonlinearity (INL) is within ±0.4 LSB. For the normal mode, the Spurious Free Dynamic range (SFDR) is larger than 40 dB; for the mixing mode, output bandwidth is up to 1.8 GHz, and the SFDR is larger than 30 dB. Under a supply voltage of 5 Volts, the output swing is 1.1 Vpp, and the total power consumption is 1.7 Walts for both channels working.

Triangular Active Charge Injection Method for Resonant Power Supply Noise Reduction

This paper proposes a triangular active charge injection method to reduce resonant power supply noise by injecting the adequate amount of charge into the supply line of the LSI in response to the current consumption of the core circuit. The proposed circuit is composed of three key components, a voltage drop detector, an injection controller circuit and a canceling capacitor circuit. In addition to the theoretical analysis of the proposed method, the measurement results indicate that our proposed method with active capacitor can realize about 14% noise reduction compared with the original noise amplitude. The proposed circuit consumes 25.2 mW in steady state and occupies 0.182 mm2.

Compact High-Isolation LTCC Diplexer Using Common Stub-Loaded Resonator With Controllable Frequencies and Bandwidths

In this paper, a low-temperature co-fired ceramic (LTCC) diplexer is presented with compact size and high isolation. By using the common stub-loaded resonator shared by two channel filters, combining and matching networks are eliminated and only three resonators are used to design the two second-order channel filters, resulting in simple structure and miniaturized size. A novel transmission path is utilized to not only realize the higher channel filter but also prevent the signal at the lower frequency band. And a specific coupling region is selected to simultaneously realize the coupling strength required by lower channel filter and a transmission zero at higher-band frequency. In this way, each channel filter can generate a transmission zero at the passband frequency of the other channel filter, resulting in high isolation. Moreover, the bandwidths and center frequencies of the two channel filters can be individually controlled due to the design flexibility of the multilayer LTCC structure. For demonstration, a diplexer operating at 3.5 and 5.5 GHz is fabricated. The core circuit has the compact size of 1.9 mm $\times1.7$ mm $\times2$ mm or $0.054~\lambda _{g} \times 0.048 \lambda _{g} \times 0.057~\lambda _{g}$ . Within the 3-dB passbands of the lower and higher channel filters, the measured isolation levels are better than 40 and 45 dB, respectively.

A 0.31-pJ/bit 20-Gb/s DFE With 1 Discrete Tap and 2 IIR Filters Feedback in 40-nm-LP CMOS

This brief presents a low-power 20-Gb/s decision feedback equalizer (DFE) with one discrete tap and two infinite impulse response (IIR) filters feedback. The advantage of the IIR-DFE lies in both great energy and area efficiency for large channel attenuations. To further enhance the power efficiency of the IIR-DFE, the charge-steering logic (CSL) is utilized in this brief. Besides, the quarter-rate topology is adopted to alleviate the race condition of the CSL-based DFE. Fabricated in a 40-nm-LP CMOS process, the DFE core circuits only consumes 6.2 mW from the 1-V supply. Moreover, the core entirely occupies an area of 5700 $\mu {\mathrm{ m}}^{2}$ . Measured with PRBS7, the bit error rates are all less than $10^{-12}$ for channel loss from −7.98 to −18.3 dB. Finally, the power efficiency of this IIR-DFE is 0.31 pJ/bit.

A Temperature Compensated Triple-Path PLL With $K_{\mathrm {VCO}}$ Non-Linearity Desensitization Capable of Operating at 77 K

A novel triple-path PLL (TPPLL) is presented to compensate the VCO frequency drift caused by the large temperature variations meanwhile maintaining a stable bandwidth and good jitter performance. The proposed PLL architecture splits the VCO tuning loop into three paths as the proportional, the integral, and the temperature compensation (TC) path, respectively. The feed-forward TC path with a large VCO gain but a small bandwidth is adopted to realize the compensation for the VCO frequency temperature drift in a closed-loop manner without affecting the high-frequency performance of the VCO. The fixed control voltage on the proportional path and limited control-voltage variation on the integral path desensitize the VCO gain (K <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">VCO</sub> ) non-linearity and stabilizes the loop bandwidth over large temperature range. The small VCO gain on the proportional and integral paths contributes to low phase noise and spurs. In addition, the different gain settings for the separate proportional and integral paths work as a capacitor multiplier, leading to saving on the silicon area of the loop filter. A prototype TPPLL at 2.56 GHz using a 65-nm CMOS process has been implemented and measured. The core circuits occupy an area of 0.08 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> , and consume 8.5 mW. The silicon measurement results show that this PLL can continuously work (without calibration) when the temperature changes from 300 K down to 77 K, and has a frequency drift reduction by 99%, while keeping good jitter performance across the entire temperature range.

The PAR proteins: from molecular circuits to dynamic self-stabilizing cell polarity.

PAR proteins constitute a highly conserved network of scaffolding proteins, adaptors and enzymes that form and stabilize cortical asymmetries in response to diverse inputs. They function throughout development and across the metazoa to regulate cell polarity. In recent years, traditional approaches to identifying and characterizing molecular players and interactions in the PAR network have begun to merge with biophysical, theoretical and computational efforts to understand the network as a pattern-forming biochemical circuit. Here, we summarize recent progress in the field, focusing on recent studies that have characterized the core molecular circuitry, circuit design and spatiotemporal dynamics. We also consider some of the ways in which the PAR network has evolved to polarize cells in different contexts and in response to different cues and functional constraints.

A High Slew-Rate Adaptive Biasing Hybrid Envelope Tracking Supply Modulator for LTE Applications

A linear-switch mode hybrid envelope tracking (ET) supply modulator utilizing adaptive biasing and gain enhanced current mirror operational transconductance amplifier (OTA) with class AB output stage in parallel with a switching regulator is presented. In comparison to a conventional OTA design with similar quiescent current consumption, proposed approach improves positive and negative slew rate from 50 to 93.4 V/ $\mu \text{s}$ and −87 to −152.5 V/ $\mu \text{s}$ , respectively, dc gain from 45 to 67 dB while consuming same amount of quiescent current. The proposed hybrid supply modulator achieves 83% peak efficiency, power-added efficiency (PAE) of 42.3% at 26.2 dBm for a 10-MHz 7.24-dB peak-to-average power ratio (PAPR) long-term evolution (LTE) signal and improves PAE by 8% at 6 dB back off from 26.2-dBm power amplifier (PA) output power with respect to fixed supply. With a 10-MHz 7.24-dB PAPR quadrature-phase shift keying LTE signal the ET PA system achieves adjacent channel leakage ratio (ACLR) of −37.7 dBc and error vector magnitude (EVM) of 4.5% at 26.2-dBm PA output power, while with a 10-MHz 8.15-dB PAPR 64QAM LTE signal the ET PA system achieves ACLR of −35.6 dBc and EVM of 6% at 26-dBm PA output power without digital predistortion. The proposed supply modulator core circuit occupies 1.1-mm2 die area, and is fabricated in a 0.18- $\mu \text{m}$ CMOS technology.

A Low-Jitter Full-Rate 25-Gb/s CDR for 100-Gb/s Optical Interconnects in 0.13-μm SiGe BiCMOS

ABSTRACTA low-jitter full-rate 25-Gb/s clock and data recovery (CDR) chip for 100-Gb/s optical interconnects is proposed. Fabricated in 0.13-μm SiGe BiCMOS technology, the chip is implemented in a third-order type-II bang-bang phase-locked loop (BBPLL) topology. To achieve optimal switching speed, all SiGe heterojunction bipolar transistors (HBTs) in high-speed blocks are biased at peak fT current density. Transistors are sized by carefully balancing speed versus power consumption. Emitter-coupled logic (ECL) and current-mode logic (CML) are employed in logic components. Compared with conventional spiral inductors, the employment of RF transmission lines in resonators of the VCO reduces the area of the VCO and, thus, the whole chip, without sacrificing the performance. The core circuits occupy an area of 0.48 mm2. The CDR recovers a clock with an rms jitter of 750 fs and a peak-to-peak jitter only of 3.46 ps.

Organic physically unclonable function on flexible substrate operable at 2 V for IoT/IoE security applications

Abstract We fabricated organic ring oscillators (ROs) on a flexible substrate and utilized them as the core circuit of a physically unclonable function (PUF). An RO-PUF is a security primitive that generates unique identification numbers (IDs) by extracting the frequency variation of the RO. We fabricated two RO-PUFs and evaluated their IDs in terms of stability and uniqueness at various operating voltages. The experimental results indicate that our RO-PUFs have a high degree of uniqueness and exhibit good stability relative to voltage fluctuations with a nominal operating voltage below 2 V.

Cell Polarity in Yeast.

A conserved molecular machinery centered on the Cdc42 GTPase regulates cell polarity in diverse organisms. Here we review findings from budding and fission yeasts that reveal both a conserved core polarity circuit and several adaptations that each organism exploits to fulfill the needs of its lifestyle. The core circuit involves positive feedback by local activation of Cdc42 to generate a cluster of concentrated GTP-Cdc42 at the membrane. Species-specific pathways regulate the timing of polarization during the cell cycle, as well as the location and number of polarity sites.

The extended object-grasping network.

Grasping is the most important skilled motor act of primates. It is based on a series of sensorimotor transformations through which the affordances of the objects to be grasped are transformed into appropriate hand movements. It is generally accepted that a circuit formed by inferior parietal areas AIP and PFG and ventral premotor area F5 represents the core circuit for sensorimotor transformations for grasping. However, selection and control of appropriate grip should also depend on higher-order information, such as the meaning of the object to be grasped, and the overarching goal of the action in which grasping is embedded. In this review, we describe recent findings showing that specific sectors of the ventrolateral prefrontal cortex are instrumental in controlling higher-order aspects of grasping. We show that these prefrontal sectors control the premotor cortex through two main gateways: the anterior subdivision of ventral area F5-sub-area F5a-, and the pre-supplementary area (area F6). We then review functional studies showing that both F5a and F6, besides being relay stations of prefrontal information, also play specific roles in grasping. Namely, sub-area F5a is involved in stereoscopic analysis of 3D objects, and in planning cue-dependent grasping activity. As for area F6, this area appears to play a crucial role in determining when to execute the motor program encoded in the parieto-premotor circuit. The recent discovery that area F6 contains a set of neurons encoding specific grip types suggests that this area, besides controlling "when to go", also may control the grip type, i.e., "how to go". We conclude by discussing clinical syndromes affecting grasping actions and their possible mechanisms.

A 0.1–1 GHz low power RF receiver front-end with noise cancellation technique for WSN applications

A low power 0.1–1GHz RF receiver front-end composed of noise-cancelling trans-conductor stage and I/Q switch stage was presented in this paper. The RF receiver front-end chip was fabricated in 0.18µm RF CMOS. Measurement results show the receiver front-end has a conversion gain of 28.1dB at high gain mode, and the single-sideband (SSB) noise figure is 6.2dB. In the low gain mode, the conversion gain of the receiver front-end is 15.5dB and the IP1dB is −12dBm. In this design, low power consumption and low cost is achieved by current-reuse and inductor-less topology. The receiver front-end consumes only 5.2mW from a 1.8V DC supply and the chip size of the core circuit is 0.12mm2.

Current mode single-input multi-output MOSFET-only filter

In this paper, a very simple topology of a current mode MOSFET-only filter with single-input and multi-output is proposed. It is very important to emphasize that it is possible to obtain five of the filter functions, namely low-pass (LP), band-pass (BP), high-pass (HP), band-stop (BS) and all-pass (AP) using the proposed topology without using external passive elements. The core circuit of the proposed filter employs only four MOS transistors; therefore, it occupies very small chip area. It is also possible to adjust the filter gain with the biasing voltage. In addition, the circuit exhibits a very low input impedance and also high output impedances which make it possible for cascading. The MOSFET capacitances which determine the transfer functions are all grounded, so physical capacitances can be used instead of MOSFET parasitic capacitances to operate the filter at very low frequencies. Moreover, proposed filter structure has low supply voltage as 1V in order to be applicable to low voltage operations. Detailed simulation results, including noise and Monte Carlo analysis, are provided using 0.18µm TSMC technology parameters to verify the feasibility of the filter circuit.

Abstract 5568: Towards decoding the interplay between glycolysis and oxidative phosphorylation in cancer

Abstract Abnormal metabolism is a hallmark of cancer, yet its regulatory mechanism is poorly understood. Cancer cells were considered to mostly utilize glycolysis, referred to as the Warburg effect. However recent evidence suggests that oxidative phosphorylation also plays a crucial role during cancer progression. Here we utilized a systems biology approach to decipher the regulatory principle of glycolysis and oxidative phosphorylation. Integrating information from literature, we constructed a regulatory network of genes and metabolites, from which we extracted a core circuit containing HIF-1, AMPK and ROS. Our circuit analysis showed that while normal cells have an oxidative state and a glycolytic state, cancer cells can access an additional hybrid state with both metabolic modes coexisting, due to higher ROS production and/or oncogenic activation, such as RAS, MYC and c-SRC. The anti-correlation between AMPK and HIF-1 and the association of metabolic states with oncogenes were further confirmed using TCGA patient transcriptomics data of multiple cancer types and single-cell RNA-seq data of lung adenocarcinoma. We propose that the hybrid phenotype contributes to metabolic plasticity, allowing cancer cells to adapt to various microenvironments. Using model simulations, we predicted the efficacies of several metabolic cancer therapies based on their effectiveness in reducing metabolic plasticity. Our theoretical framework of metabolism can serve as a platform to decode cancer metabolic plasticity and design cancer therapies targeting metabolism. Citation Format: Dongya Jia, Linglin Yu, Mingyang Lu, Eshel Ben-Jacob, Jianpeng Ma, Herbert Levine, Benny A. Kaipparettu, Jose Onuchic. Towards decoding the interplay between glycolysis and oxidative phosphorylation in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5568. doi:10.1158/1538-7445.AM2017-5568

A linear ultra wide band low noise amplifier using pre-distortion technique

This paper presents an Ultra Wide-Band (UWB) high linear low noise amplifier. The linearity of Common Gate (CG) structure is improved based on pre-distortion technique. An auxiliary transistor is used at the input to sink the nonlinear terms of source current, resulting linearity improvement. Furthermore, an inductor is used in the gate of the main amplifying transistor, which efficiently improves gain, input matching and noise performance at higher frequencies. Detailed mathematical analysis show the effectiveness of both linearity improvement and bandwidth extension techniques. Post-layout simulation results of the proposed LNA in TSMC 0.18µm RF-CMOS process show a gain of 13.7dB with −3dB bandwidth of 0.8–10.4GHz and minimum noise figure (NF) of 3dB. Input Third Intercept Point (IIP3) of 10.3–13dBm is achieved which shows 8dB improvement compared to conventional common gate structure. The core circuit occupies an area of 0.19mm2 including bond pads, while consuming 4mA from a 1.8-V supply.

Modeling the Genetic Regulation of Cancer Metabolism: Interplay between Glycolysis and Oxidative Phosphorylation.

Abnormal metabolism is a hallmark of cancer, yet its regulation remains poorly understood. Cancer cells were considered to utilize primarily glycolysis for ATP production, referred to as the Warburg effect. However, recent evidence suggests that oxidative phosphorylation (OXPHOS) plays a crucial role during cancer progression. Here we utilized a systems biology approach to decipher the regulatory principle of glycolysis and OXPHOS. Integrating information from literature, we constructed a regulatory network of genes and metabolites, from which we extracted a core circuit containing HIF-1, AMPK, and ROS. Our circuit analysis showed that while normal cells have an oxidative state and a glycolytic state, cancer cells can access a hybrid state with both metabolic modes coexisting. This was due to higher ROS production and/or oncogene activation, such as RAS, MYC, and c-SRC. Guided by the model, we developed two signatures consisting of AMPK and HIF-1 downstream genes, respectively, to quantify the activity of glycolysis and OXPHOS. By applying the AMPK and HIF-1 signatures to The Cancer Genome Atlas patient transcriptomics data of multiple cancer types and single-cell RNA-seq data of lung adenocarcinoma, we confirmed an anticorrelation between AMPK and HIF-1 activities and the association of metabolic states with oncogenes. We propose that the hybrid phenotype contributes to metabolic plasticity, allowing cancer cells to adapt to various microenvironments. Using model simulations, our theoretical framework of metabolism can serve as a platform to decode cancer metabolic plasticity and design cancer therapies targeting metabolism. Cancer Res; 77(7); 1564-74. ©2017 AACR.

Interrogating the topological robustness of gene regulatory circuits by randomization.

One of the most important roles of cells is performing their cellular tasks properly for survival. Cells usually achieve robust functionality, for example, cell-fate decision-making and signal transduction, through multiple layers of regulation involving many genes. Despite the combinatorial complexity of gene regulation, its quantitative behavior has been typically studied on the basis of experimentally verified core gene regulatory circuitry, composed of a small set of important elements. It is still unclear how such a core circuit operates in the presence of many other regulatory molecules and in a crowded and noisy cellular environment. Here we report a new computational method, named random circuit perturbation (RACIPE), for interrogating the robust dynamical behavior of a gene regulatory circuit even without accurate measurements of circuit kinetic parameters. RACIPE generates an ensemble of random kinetic models corresponding to a fixed circuit topology, and utilizes statistical tools to identify generic properties of the circuit. By applying RACIPE to simple toggle-switch-like motifs, we observed that the stable states of all models converge to experimentally observed gene state clusters even when the parameters are strongly perturbed. RACIPE was further applied to a proposed 22-gene network of the Epithelial-to-Mesenchymal Transition (EMT), from which we identified four experimentally observed gene states, including the states that are associated with two different types of hybrid Epithelial/Mesenchymal phenotypes. Our results suggest that dynamics of a gene circuit is mainly determined by its topology, not by detailed circuit parameters. Our work provides a theoretical foundation for circuit-based systems biology modeling. We anticipate RACIPE to be a powerful tool to predict and decode circuit design principles in an unbiased manner, and to quantitatively evaluate the robustness and heterogeneity of gene expression.