Neuronal Calcium Signaling in Metabolic Regulation and Adaptation to Nutrient Stress.

PubMed

Jayakumar, Siddharth; Hasan, Gaiti

2018-01-01

All organisms can respond physiologically and behaviorally to environmental fluxes in nutrient levels. Different nutrient sensing pathways exist for specific metabolites, and their inputs ultimately define appropriate nutrient uptake and metabolic homeostasis. Nutrient sensing mechanisms at the cellular level require pathways such as insulin and target of rapamycin (TOR) signaling that integrates information from different organ systems like the fat body and the gut. Such integration is essential for coordinating growth with development. Here we review the role of a newly identified set of integrative interneurons and the role of intracellular calcium signaling within these neurons, in regulating nutrient sensing under conditions of nutrient stress. A comparison of the identified Drosophila circuit and cellular mechanisms employed in this circuit, with vertebrate systems, suggests that the identified cell signaling mechanisms may be conserved for neural circuit function related to nutrient sensing by central neurons. The ideas proposed are potentially relevant for understanding the molecular basis of metabolic disorders, because these are frequently linked to nutritional stress.

A Low Input Current and Wide Conversion Ratio Buck Regulator with 75% Efficiency for High-Voltage Triboelectric Nanogenerators

NASA Astrophysics Data System (ADS)

Luo, Li-Chuan; Bao, De-Chun; Yu, Wu-Qi; Zhang, Zhao-Hua; Ren, Tian-Ling

2016-01-01

It is meaningful to research the Triboelectric Nanogenerators (TENG), which can create electricity anywhere and anytime. There are many researches on the structures and materials of TENG to explain the phenomenon that the maximum voltage is stable and the current is increasing. The output voltage of the TENG is high about 180-400 V, and the output current is small about 39 μA, which the electronic devices directly integration of TENG with Li-ion batteries will result in huge energy loss due to the ultrahigh TENG impedance. A novel interface circuit with the high-voltage buck regulator for TENG is introduced firstly in this paper. The interface circuit can transfer the output signal of the TENG into the signal fit to a lithium ion battery. Through the circuit of the buck regulator, the average output voltage is about 4.0 V and the average output current is about 1.12 mA. Further, the reliability and availability for the lithium ion battery and the circuit are discussed. The interface circuit is simulated using the Cadence software and verified through PCB experiment. The buck regulator can achieve 75% efficiency for the High-Voltage TENG. This will lead to a research hot and industrialization applications.

General Aspects of Two-Component Regulatory Circuits in Bacteria: Domains, Signals and Roles.

PubMed

Padilla-Vaca, Felipe; Mondragón-Jaimes, Verónica; Franco, Bernardo

2017-01-01

All living organisms are subject to changing environments, which must be sensed in order to respond swiftly and efficiently. Two-component systems (TCS) are signal transduction regulatory circuits based typically on a membrane bound sensor kinase and a cytoplasmic response regulator, that is activated through a histidine to aspartate phosphorelay reactions. Activated response regulator acts usually as a transcription factor. The best known examples were identified in bacteria, but they are also found in fungi, algae and plants. Thus far, they are not found in mammals. Regulatory circuits coupled to two-component systems exhibit a myriad of responses to environmental stimuli such as: redox potential, pH, specific metabolites, pressure, light and more recently to specific antimicrobial peptides that activate a sensor kinase responsible for expressing virulence factors through the active response regulator. In this review we explore general aspects on two-component systems that ultimately can play a role on virulence regulation, also the intriguing domain properties of the sensor kinases that can be a potential target for antimicrobial compounds. Only a handful of sensor kinases are extensively characterized, the vast majority belong to what we call 'the dark matter of bacterial signal transduction' since no known signal, structure and biochemical properties are available. Regulatory circuits from vertebrate pathogenic organisms can explain virulence in terms of either response to environmental factors or specific niche occupancy. Hopefully, knowledge on these signal transduction systems can lead to identify novel molecules that target two-component systems, since the increase of drug resistant microorganisms is worrisome. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A regulatory circuit of miR-125b/miR-20b and Wnt signalling controls glioblastoma phenotypes through FZD6-modulated pathways

PubMed Central

Huang, Tianzhi; Alvarez, Angel A.; Pangeni, Rajendra P.; M. Horbinski, Craig; Lu, Songjian; Kim, Sung-Hak; James, C. David; J. Raizer, Jeffery; A. Kessler, John; Brenann, Cameron W.; Sulman, Erik P.; Finocchiaro, Gaetano; Tan, Ming; Nishikawa, Ryo; Lu, Xinghua; Nakano, Ichiro; Hu, Bo; Cheng, Shi-Yuan

2016-01-01

Molecularly defined subclassification is associated with phenotypic malignancy of glioblastoma (GBM). However, current understanding of the molecular basis of subclass conversion that is often involved in GBM recurrence remain rudimentary at best. Here we report that canonical Wnt signalling that is active in proneural (PN) but inactive in mesenchymal (MES) GBM, along with miR-125b and miR-20b that are expressed at high levels in PN compared with MES GBM, comprise a regulatory circuit involving TCF4-miR-125b/miR-20b-FZD6. FZD6 acts as a negative regulator of this circuit by activating CaMKII–TAK1–NLK signalling, which, in turn, attenuates Wnt pathway activity while promoting STAT3 and NF-κB signalling that are important regulators of the MES-associated phenotype. These findings are confirmed by targeting differentially enriched pathways in PN versus MES GBM that results in inhibition of distinct GBM subtypes. Correlative expressions of the components of this circuit are prognostic relevant for clinical GBM. Our findings provide insights for understanding GBM pathogenesis and for improving treatment of GBM. PMID:27698350

Regulation of lipid metabolism by energy availability: a role for the central nervous system.

PubMed

Nogueiras, R; López, M; Diéguez, C

2010-03-01

The central nervous system (CNS) is crucial in the regulation of energy homeostasis. Many neuroanatomical studies have shown that the white adipose tissue (WAT) is innervated by the sympathetic nervous system, which plays a critical role in adipocyte lipid metabolism. Therefore, there are currently numerous reports indicating that signals from the CNS control the amount of fat by modulating the storage or oxidation of fatty acids. Importantly, some CNS pathways regulate adipocyte metabolism independently of food intake, suggesting that some signals possess alternative mechanisms to regulate energy homeostasis. In this review, we mainly focus on how neuronal circuits within the hypothalamus, such as leptin- ghrelin-and resistin-responsive neurons, as well as melanocortins, neuropeptide Y, and the cannabinoid system exert their actions on lipid metabolism in peripheral tissues such as WAT, liver or muscle. Dissecting the complicated interactions between peripheral signals and neuronal circuits regulating lipid metabolism might open new avenues for the development of new therapies preventing and treating obesity and its associated cardiometabolic sequelae.

A Genetic RNAi Screen for IP3/Ca2+ Coupled GPCRs in Drosophila Identifies the PdfR as a Regulator of Insect Flight

PubMed Central

Agrawal, Tarjani; Sadaf, Sufia; Hasan, Gaiti

2013-01-01

Insect flight is regulated by various sensory inputs and neuromodulatory circuits which function in synchrony to control and fine-tune the final behavioral outcome. The cellular and molecular bases of flight neuromodulatory circuits are not well defined. In Drosophila melanogaster, it is known that neuronal IP3 receptor mediated Ca2+ signaling and store-operated Ca2+ entry (SOCE) are required for air-puff stimulated adult flight. However, G-protein coupled receptors (GPCRs) that activate intracellular Ca2+ signaling in the context of flight are unknown in Drosophila. We performed a genetic RNAi screen to identify GPCRs that regulate flight by activating the IP3 receptor. Among the 108 GPCRs screened, we discovered 5 IP3/Ca2+ linked GPCRs that are necessary for maintenance of air-puff stimulated flight. Analysis of their temporal requirement established that while some GPCRs are required only during flight circuit development, others are required both in pupal development as well as during adult flight. Interestingly, our study identified the Pigment Dispersing Factor Receptor (PdfR) as a regulator of flight circuit development and as a modulator of acute flight. From the analysis of PdfR expressing neurons relevant for flight and its well-defined roles in other behavioral paradigms, we propose that PdfR signaling functions systemically to integrate multiple sensory inputs and modulate downstream motor behavior. PMID:24098151

Submicrosecond Power-Switching Test Circuit

NASA Technical Reports Server (NTRS)

Folk, Eric N.

2006-01-01

A circuit that changes an electrical load in a switching time shorter than 0.3 microsecond has been devised. This circuit can be used in testing the regulation characteristics of power-supply circuits . especially switching power-converter circuits that are supposed to be able to provide acceptably high degrees of regulation in response to rapid load transients. The combination of this power-switching circuit and a known passive constant load could be an attractive alternative to a typical commercially available load-bank circuit that can be made to operate in nominal constant-voltage, constant-current, and constant-resistance modes. The switching provided by a typical commercial load-bank circuit in the constant-resistance mode is not fast enough for testing of regulation in response to load transients. Moreover, some test engineers do not trust the test results obtained when using commercial load-bank circuits because the dynamic responses of those circuits are, variously, partly unknown and/or excessively complex. In contrast, the combination of this circuit and a passive constant load offers both rapid switching and known (or at least better known) load dynamics. The power-switching circuit (see figure) includes a signal-input section, a wide-hysteresis Schmitt trigger that prevents false triggering in the event of switch-contact bounce, a dual-bipolar-transistor power stage that drives the gate of a metal oxide semiconductor field-effect transistor (MOSFET), and the MOSFET, which is the output device that performs the switching of the load. The MOSFET in the specific version of the circuit shown in the figure is rated to stand off a potential of 100 V in the "off" state and to pass a current of 20 A in the "on" state. The switching time of this circuit (the characteristic time of rise or fall of the potential at the drain of the MOSFET) is .300 ns. The circuit can accept any of three control inputs . which one depending on the test that one seeks to perform: a repetitive waveform from a signal generator, momentary closure of a push-button switch, or closure or opening of a manually operated on/off switch. In the case of a signal generator, one can adjust the frequency and duty cycle as needed to obtain the desired AC power-supply response, which one could display on an oscilloscope. Momentary switch closure could be useful for obtaining (and, if desired, displaying on an oscilloscope set to trigger on an event) the response of a power supply to a single load transient. The on/off switch can be used to switch between load states in which static-load regulation measurements are performed.

Stochastic modular analysis for gene circuits: interplay among retroactivity, nonlinearity, and stochasticity.

PubMed

Kim, Kyung Hyuk; Sauro, Herbert M

2015-01-01

This chapter introduces a computational analysis method for analyzing gene circuit dynamics in terms of modules while taking into account stochasticity, system nonlinearity, and retroactivity. (1) ANALOG ELECTRICAL CIRCUIT REPRESENTATION FOR GENE CIRCUITS: A connection between two gene circuit components is often mediated by a transcription factor (TF) and the connection signal is described by the TF concentration. The TF is sequestered to its specific binding site (promoter region) and regulates downstream transcription. This sequestration has been known to affect the dynamics of the TF by increasing its response time. The downstream effect-retroactivity-has been shown to be explicitly described in an electrical circuit representation, as an input capacitance increase. We provide a brief review on this topic. (2) MODULAR DESCRIPTION OF NOISE PROPAGATION: Gene circuit signals are noisy due to the random nature of biological reactions. The noisy fluctuations in TF concentrations affect downstream regulation. Thus, noise can propagate throughout the connected system components. This can cause different circuit components to behave in a statistically dependent manner, hampering a modular analysis. Here, we show that the modular analysis is still possible at the linear noise approximation level. (3) NOISE EFFECT ON MODULE INPUT-OUTPUT RESPONSE: We investigate how to deal with a module input-output response and its noise dependency. Noise-induced phenotypes are described as an interplay between system nonlinearity and signal noise. Lastly, we provide the comprehensive approach incorporating the above three analysis methods, which we call "stochastic modular analysis." This method can provide an analysis framework for gene circuit dynamics when the nontrivial effects of retroactivity, stochasticity, and nonlinearity need to be taken into account.

A Rhizobium radiobacter Histidine Kinase Can Employ Both Boolean AND and OR Logic Gates to Initiate Pathogenesis.

PubMed

Fang, Fang; Lin, Yi-Han; Pierce, B Daniel; Lynn, David G

2015-10-12

The molecular logic gates that regulate gene circuits are necessarily intricate and highly regulated, particularly in the critical commitments necessary for pathogenesis. We now report simple AND and OR logic gates to be accessible within a single protein receptor. Pathogenesis by the bacterium Rhizobium radiobacter is mediated by a single histidine kinase, VirA, which processes multiple small molecule host signals (phenol and sugar). Mutagenesis analyses converged on a single signal integration node, and finer functional analyses revealed that a single residue could switch VirA from a functional AND logic gate to an OR gate where each of two signals activate independently. Host range preferences among natural strains of R. radiobacter correlate with these gate logic strategies. Although the precise mechanism for the signal integration node requires further analyses, long-range signal transmission through this histidine kinase can now be exploited for synthetic signaling circuits. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Method and apparatus to provide power conversion with high power factor

DOEpatents

Perreault, David J.; Lim, Seungbum; Otten, David M.

2017-05-23

A power converter circuit rectifies a line voltage and applies the rectified voltage to a stack of capacitors. Voltages on the capacitors are coupled to a plurality of regulating converters to be converted to regulated output signals. The regulated output signals are combined and converted to a desired DC output voltage of the power converter. Input currents of the regulating converters are modulated in a manner that enhances the power factor of the power converter.

Engineering entropy-driven reactions and networks catalyzed by DNA.

PubMed

Zhang, David Yu; Turberfield, Andrew J; Yurke, Bernard; Winfree, Erik

2007-11-16

Artificial biochemical circuits are likely to play as large a role in biological engineering as electrical circuits have played in the engineering of electromechanical devices. Toward that end, nucleic acids provide a designable substrate for the regulation of biochemical reactions. However, it has been difficult to incorporate signal amplification components. We introduce a design strategy that allows a specified input oligonucleotide to catalyze the release of a specified output oligonucleotide, which in turn can serve as a catalyst for other reactions. This reaction, which is driven forward by the configurational entropy of the released molecule, provides an amplifying circuit element that is simple, fast, modular, composable, and robust. We have constructed and characterized several circuits that amplify nucleic acid signals, including a feedforward cascade with quadratic kinetics and a positive feedback circuit with exponential growth kinetics.

Adipostatic regulation of motivation and emotion.

PubMed

Davis, Jon F

2010-05-01

The proper maintenance of body weight and mood are two of the most prevalent health issues present in society today. Obese humans display higher levels of mood-related disorders and the causality of such an association is unknown. A common feature of obesity is the imbalance of regulatory hormones which normally act to maintain stable energy balance and body weight. The adiposity hormone leptin is one such signal elevated in obesity with the capacity to dampen feeding behavior through action on brain circuits which regulate appetite and metabolism. Recent evidence suggests that leptin may regulate motivation through its actions within brain reward circuitry. In addition, leptin signaling within central nervous system regions that regulate cognition and emotion elicits anti-depressant like effects. Together, these data indicate that leptin may regulate the decreased motivation and mood present in obesity and depression. This review describes the capacity of leptin to regulate motivation and depression through actions within brain circuits that modulate effort-based behavior and emotion, respectively.

Modulatory compartments in cortex and local regulation of cholinergic tone.

PubMed

Coppola, Jennifer J; Ward, Nicholas J; Jadi, Monika P; Disney, Anita A

2016-09-01

Neuromodulatory signaling is generally considered broad in its impact across cortex. However, variations in the characteristics of cortical circuits may introduce regionally-specific responses to diffuse modulatory signals. Features such as patterns of axonal innervation, tissue tortuosity and molecular diffusion, effectiveness of degradation pathways, subcellular receptor localization, and patterns of receptor expression can lead to local modification of modulatory inputs. We propose that modulatory compartments exist in cortex and can be defined by variation in structural features of local circuits. Further, we argue that these compartments are responsible for local regulation of neuromodulatory tone. For the cholinergic system, these modulatory compartments are regions of cortical tissue within which signaling conditions for acetylcholine are relatively uniform, but between which signaling can vary profoundly. In the visual system, evidence for the existence of compartments indicates that cholinergic modulation likely differs across the visual pathway. We argue that the existence of these compartments calls for thinking about cholinergic modulation in terms of finer-grained control of local cortical circuits than is implied by the traditional view of this system as a diffuse modulator. Further, an understanding of modulatory compartments provides an opportunity to better understand and perhaps correct signal modifications that lead to pathological states. Copyright © 2016 Elsevier Ltd. All rights reserved.

High stability buffered phase comparator

NASA Technical Reports Server (NTRS)

Adams, W. A.; Reinhardt, V. S. (Inventor)

1984-01-01

A low noise RF signal phase comparator comprised of two high stability driver buffer amplifiers driving a double balanced mixer which operate to generate a beat frequency between the two RF input signals coupled to the amplifiers from the RF sources is described. The beat frequency output from the mixer is applied to a low noise zero crossing detector which is the phase difference between the two RF inputs. Temperature stability is provided by mounting the amplifiers and mixer on a common circuit board with the active circuit elements located on one side of a circuit board and the passive circuit elements located on the opposite side. A common heat sink is located adjacent the circuit board. The active circuit elements are embedded into the bores of the heat sink which slows the effect of ambient temperature changes and reduces the temperature gradients between the active circuit elements, thus improving the cancellation of temperature effects. The two amplifiers include individual voltage regulators, which increases RF isolation.

SIFamide Translates Hunger Signals into Appetitive and Feeding Behavior in Drosophila.

PubMed

Martelli, Carlotta; Pech, Ulrike; Kobbenbring, Simon; Pauls, Dennis; Bahl, Britta; Sommer, Mirjam Vanessa; Pooryasin, Atefeh; Barth, Jonas; Arias, Carmina Warth Perez; Vassiliou, Chrystalleni; Luna, Abud Jose Farca; Poppinga, Haiko; Richter, Florian Gerhard; Wegener, Christian; Fiala, André; Riemensperger, Thomas

2017-07-11

Animal behavior is, on the one hand, controlled by neuronal circuits that integrate external sensory stimuli and induce appropriate motor responses. On the other hand, stimulus-evoked or internally generated behavior can be influenced by motivational conditions, e.g., the metabolic state. Motivational states are determined by physiological parameters whose homeostatic imbalances are signaled to and processed within the brain, often mediated by modulatory peptides. Here, we investigate the regulation of appetitive and feeding behavior in the fruit fly, Drosophila melanogaster. We report that four neurons in the fly brain that release SIFamide are integral elements of a complex neuropeptide network that regulates feeding. We show that SIFamidergic cells integrate feeding stimulating (orexigenic) and feeding suppressant (anorexigenic) signals to appropriately sensitize sensory circuits, promote appetitive behavior, and enhance food intake. Our study advances the cellular dissection of evolutionarily conserved signaling pathways that convert peripheral metabolic signals into feeding-related behavior. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Gap Junction-Mediated Signaling from Motor Neurons Regulates Motor Generation in the Central Circuits of Larval Drosophila.

PubMed

Matsunaga, Teruyuki; Kohsaka, Hiroshi; Nose, Akinao

2017-02-22

In this study, we used the peristaltic crawling of Drosophila larvae as a model to study how motor patterns are regulated by central circuits. We built an experimental system that allows simultaneous application of optogenetics and calcium imaging to the isolated ventral nerve cord (VNC). We then investigated the effects of manipulating local activity of motor neurons (MNs) on fictive locomotion observed as waves of MN activity propagating along neuromeres. Optical inhibition of MNs with halorhodopsin3 in a middle segment (A4, A5, or A6), but not other segments, dramatically decreased the frequency of the motor waves. Conversely, local activation of MNs with channelrhodopsin2 in a posterior segment (A6 or A7) increased the frequency of the motor waves. Since peripheral nerves mediating sensory feedback were severed in the VNC preparation, these results indicate that MNs send signals to the central circuits to regulate motor pattern generation. Our results also indicate segmental specificity in the roles of MNs in motor control. The effects of the local MN activity manipulation were lost in shaking-B 2 ( shakB 2 ) or ogre 2 , gap-junction mutations in Drosophila , or upon acute application of the gap junction blocker carbenoxolone, implicating electrical synapses in the signaling from MNs. Cell-type-specific RNAi suggested shakB and ogre function in MNs and interneurons, respectively, during the signaling. Our results not only reveal an unexpected role for MNs in motor pattern regulation, but also introduce a powerful experimental system that enables examination of the input-output relationship among the component neurons in this system. SIGNIFICANCE STATEMENT Motor neurons are generally considered passive players in motor pattern generation, simply relaying information from upstream interneuronal circuits to the target muscles. This study shows instead that MNs play active roles in the control of motor generation by conveying information via gap junctions to the central pattern-generating circuits in larval Drosophila , providing novel insights into motor circuit control. The experimental system introduced in this study also presents a new approach for studying intersegmentally coordinated locomotion. Unlike traditional electrophysiology methods, this system enables the simultaneous recording and manipulation of populations of neurons that are genetically specified and span multiple segments. Copyright © 2017 the authors 0270-6474/17/372045-16$15.00/0.

A High Performance 50% Clock Duty Cycle Regulator

NASA Astrophysics Data System (ADS)

Huang, Peng; Deng, Hong-Hui; Yin, Yong-Sheng

A low-jitter clock duty cycle corrector circuit applied in high performance ADC is presented in the paper, such circuits can change low accuracy input signals with different frequencies into 50% pulse width clock. The result have show that the circuit could lock duty cycle rapidly with an accuracy of 50% ± 1% in 200ns. This circuit have 10%-90% of duty cycle input, and clock jitter could be suppressed to less than 5ps. The method used in the circuit, which provides little relationship with the noise and process mismatch, is widely used Implemented in 0.18μm CMOS process.

Control of excessive neural circuit excitability and prevention of epileptic seizures by endocannabinoid signaling.

PubMed

Sugaya, Yuki; Kano, Masanobu

2018-05-08

Progress in research on endocannabinoid signaling has greatly advanced our understanding of how it controls neural circuit excitability in health and disease. In general, endocannabinoid signaling at excitatory synapses suppresses seizures by inhibiting glutamate release. In contrast, endocannabinoid signaling promotes seizures by inhibiting GABA release at inhibitory synapses. The physiological distribution of endocannabinoid signaling molecules becomes disrupted with the development of epileptic focus in patients with mesial temporal lobe epilepsy and in animal models of experimentally induced epilepsy. Augmentation of endocannabinoid signaling can promote the development of epileptic focus at initial stages. However, at later stages, increased endocannabinoid signaling delays it and suppresses spontaneous seizures. Thus, the regulation of endocannabinoid signaling at specific synapses that cause hyperexcitability during particular stages of disease development may be effective for treating epilepsy and epileptogenesis.

Adenosine signaling in striatal circuits and alcohol use disorders.

PubMed

Nam, Hyung Wook; Bruner, Robert C; Choi, Doo-Sup

2013-09-01

Adenosine signaling has been implicated in the pathophysiology of alcohol use disorders and other psychiatric disorders such as anxiety and depression. Numerous studies have indicated a role for A1 receptors (A1R) in acute ethanol-induced motor incoordination, while A2A receptors (A2AR) mainly regulate the rewarding effect of ethanol in mice. Recent findings have demonstrated that dampened A2AR-mediated signaling in the dorsomedial striatum (DMS) promotes ethanol-seeking behaviors. Moreover, decreased A2AR function is associated with decreased CREB activity in the DMS, which enhances goal-oriented behaviors and contributes to excessive ethanol drinking in mice. Interestingly, caffeine, the most commonly used psychoactive substance, is known to inhibit both the A1R and A2AR. This dampened adenosine receptor function may mask some of the acute intoxicating effects of ethanol. Furthermore, based on the fact that A2AR activity plays a role in goal-directed behavior, caffeine may also promote ethanol-seeking behavior. The A2AR is enriched in the striatum and exclusively expressed in striatopallidal neurons, which may be responsible for the regulation of inhibitory behavioral control over drug rewarding processes through the indirect pathway of the basal ganglia circuit. Furthermore, the antagonistic interactions between adenosine and dopamine receptors in the striatum also play an integral role in alcoholism and addiction-related disorders. This review focuses on regulation of adenosine signaling in striatal circuits and the possible implication of caffeine in goal-directed behaviors and addiction.

BiCMOS circuit technology for a 704 MHz ATM switch LSI

NASA Astrophysics Data System (ADS)

Ohtomo, Yusuke; Yasuda, Sadayuki; Togashi, Minoru; Ino, Masayuki; Tanabe, Yasuyuki; Inoue, Jun-Ichi; Nogawa, Masafumi; Hino, Shigeki

1994-05-01

This paper describes BiCMOS level-converter circuits and clock circuits that increase VLSI interface speed to 1 GHz, and their application to a 704 MHz ATM switch LSI. An LSI with high speed interface requires a BiCMOS multiplexer/demultiplexer (MUX/DEMUX) on the chip to reduce internal operation speed. A MUX/DEMUX with minimum power dissipation and a minimum pattern area can be designed using the proposed converter circuits. The converter circuits, using weakly cross-coupled CMOS inverters and a voltage regulator circuit, can convert signal levels between LCML and positive CMOS at a speed of 500 MHz. Data synchronization in the high speed region is ensured by a new BiCMOS clock circuit consisting of a pure ECL path and retiming circuits. The clock circuit reduces the chip latency fluctuation of the clock signal and absorbs the delay difference between the ECL clock and data through the CMOS circuits. A rerouting-Banyan (RRB) ATM switch, employing both the proposed converter circuits and the clock circuits, has been fabricated with 0.5 micron BiCMOS technology. The LSI, composed of CMOS 15 K gate LOGIC, 8 Kb RAM, 1 Kb FIFO and ECL 1.6 K gate LOGIC, achieved an operation speed of 704-MHz with power dissipation of 7.2 W.

Cholinergic signaling controls conditioned-fear behaviors and enhances plasticity of cortical-amygdala circuits

PubMed Central

Jiang, Li; Kundu, Srikanya; Lederman, James D.; López-Hernández, Gretchen Y.; Ballinger, Elizabeth C.; Wang, Shaohua; Talmage, David A.; Role, Lorna W.

2016-01-01

Summary We examined the contribution of endogenous cholinergic signaling to the acquisition and extinction of fear- related memory by optogenetic regulation of cholinergic input to the basal lateral amygdala (BLA). Stimulation of cholinergic terminal fields within the BLA in awake-behaving mice during training in a cued fear-conditioning paradigm slowed the extinction of learned fear as assayed by multi-day retention of extinction learning. Inhibition of cholinergic activity during training reduced the acquisition of learned fear behaviors. Circuit mechanisms underlying the behavioral effects of cholinergic signaling in the BLA were assessed by in vivo and ex vivo electrophysiological recording. Photo-stimulation of endogenous cholinergic input: (1) enhances firing of putative BLA principal neurons through activation of acetylcholine receptors (AChRs); (2) enhances glutamatergic synaptic transmission in the BLA and (3) induces LTP of cortical-amygdala circuits. These studies support an essential role of cholinergic modulation of BLA circuits in the inscription and retention of fear memories. PMID:27161525

The autism associated MET receptor tyrosine kinase engages early neuronal growth mechanism and controls glutamatergic circuits development in the forebrain

PubMed Central

Peng, Yun; Lu, Zhongming; Li, Guohui; Piechowicz, Mariel; Anderson, Miranda; Uddin, Yasin; Wu, Jie; Qiu, Shenfeng

2015-01-01

The human MET gene imparts a replicated risk for autism spectrum disorder (ASD), and is implicated in the structural and functional integrity of brain. MET encodes a receptor tyrosine kinase, MET, which plays a pleiotropic role in embryogenesis and modifies a large number of neurodevelopmental events. Very little is known, however, on how MET signaling engages distinct cellular events to collectively affect brain development in ASD-relevant disease domains. Here, we show that MET protein expression is dynamically regulated and compartmentalized in developing neurons. MET is heavily expressed in neuronal growth cones at early developmental stages and its activation engages small GTPase Cdc42 to promote neuronal growth, dendritic arborization, and spine formation. Genetic ablation of MET signaling in mouse dorsal pallium leads to altered neuronal morphology indicative of early functional maturation. In contrast, prolonged activation of MET represses the formation and functional maturation of glutamatergic synapses. Moreover, manipulating MET signaling levels in vivo in the developing prefrontal projection neurons disrupts the local circuit connectivity made onto these neurons. Therefore, normal time-delimited MET signaling is critical in regulating the timing of neuronal growth, glutamatergic synapse maturation and cortical circuit function. Dysregulated MET signaling may lead to pathological changes in forebrain maturation and connectivity, and thus contribute to the emergence of neurological symptoms associated with ASD. PMID:26728565

A C. elegans Thermosensory Circuit Regulates Longevity through crh-1/CREB-Dependent flp-6 Neuropeptide Signaling.

PubMed

Chen, Yen-Chih; Chen, Hung-Jhen; Tseng, Wei-Chin; Hsu, Jiun-Min; Huang, Tzu-Ting; Chen, Chun-Hao; Pan, Chun-Liang

2016-10-24

Sensory perception, including thermosensation, shapes longevity in diverse organisms, but longevity-modulating signals from the sensory neurons are largely obscure. Here we show that CRH-1/CREB activation by CMK-1/CaMKI in the AFD thermosensory neuron is a key mechanism that maintains lifespan at warm temperatures in C. elegans. In response to temperature rise and crh-1 activation, the AFD neurons produce and secrete the FMRFamide neuropeptide FLP-6. Both CRH-1 and FLP-6 are necessary and sufficient for longevity at warm temperatures. Our data suggest that FLP-6 targets the AIY interneurons and engages DAF-9 sterol hormone signaling. Moreover, we show that FLP-6 signaling downregulates ins-7/insulin-like peptide and several insulin pathway genes, whose activity compromises lifespan. Our work illustrates how temperature experience is integrated by the thermosensory circuit to generate neuropeptide signals that remodel insulin and sterol hormone signaling and reveals a neuronal-endocrine circuit driven by thermosensation to promote temperature-specific longevity. Copyright © 2016 Elsevier Inc. All rights reserved.

Dynamics of Gut-Brain Communication Underlying Hunger.

PubMed

Beutler, Lisa R; Chen, Yiming; Ahn, Jamie S; Lin, Yen-Chu; Essner, Rachel A; Knight, Zachary A

2017-10-11

Communication between the gut and brain is critical for homeostasis, but how this communication is represented in the dynamics of feeding circuits is unknown. Here we describe nutritional regulation of key neurons that control hunger in vivo. We show that intragastric nutrient infusion rapidly and durably inhibits hunger-promoting AgRP neurons in awake, behaving mice. This inhibition is proportional to the number of calories infused but surprisingly independent of macronutrient identity or nutritional state. We show that three gastrointestinal signals-serotonin, CCK, and PYY-are necessary or sufficient for these effects. In contrast, the hormone leptin has no acute effect on dynamics of these circuits or their sensory regulation but instead induces a slow modulation that develops over hours and is required for inhibition of feeding. These findings reveal how layers of visceral signals operating on distinct timescales converge on hypothalamic feeding circuits to generate a central representation of energy balance. Copyright © 2017 Elsevier Inc. All rights reserved.

Solid state light source driver establishing buck or boost operation

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

Palmer, Fred

A solid state light source driver circuit that operates in either a buck convertor or a boost convertor configuration is provided. The driver circuit includes a controller, a boost switch circuit and a buck switch circuit, each coupled to the controller, and a feedback circuit, coupled to the light source. The feedback circuit provides feedback to the controller, representing a DC output of the driver circuit. The controller controls the boost switch circuit and the buck switch circuit in response to the feedback signal, to regulate current to the light source. The controller places the driver circuit in its boostmore » converter configuration when the DC output is less than a rectified AC voltage coupled to the driver circuit at an input node. The controller places the driver circuit in its buck converter configuration when the DC output is greater than the rectified AC voltage at the input node.« less

Design and simulation of proportional biological operational Mu-circuit.

PubMed

Xu, Dechang; Cai, Zhipeng; Liu, Ke; Zeng, Xiangmiao; Ouyang, Yujing; Dai, Cuihong; Hou, Aiju; Cheng, Dayou; Li, Jianzhong

2015-03-01

It is challenging yet desirable to quantitatively control the expression of a target gene in practice. We design a device-Proportional Biological Operational Mu-circuit (P-BOM) incorporating AND/OR gate and operational amplifier into one circuit and explore its behaviors through simulation. The results imply that will be possible to regulate input-output proportionally by manipulating the RBS of hrpR, hrpS, tetR and output gene and used in the sensing of environmental weak signals such as dioxins.

Phosphodiesterase inhibition and modulation of corticostriatal and hippocampal circuits: Clinical overview and translational considerations.

PubMed

Heckman, P R A; Blokland, A; Bollen, E P P; Prickaerts, J

2018-04-01

The corticostriatal and hippocampal circuits contribute to the neurobiological underpinnings of several neuropsychiatric disorders, including Alzheimer's disease, Parkinson's disease and schizophrenia. Based on biological function, these circuits can be clustered into motor circuits, associative/cognitive circuits and limbic circuits. Together, dysfunctions in these circuits produce the wide range of symptoms observed in related neuropsychiatric disorders. Intracellular signaling in these circuits is largely mediated through the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway with an additional role for the cyclic guanosine monophosphate (cGMP)/ protein kinase G (PKG) pathway, both of which can be regulated by phosphodiesterase inhibitors (PDE inhibitors). Through their effects on cAMP response element-binding protein (CREB) and Dopamine- and cAMP-Regulated PhosphoProtein MR 32 kDa (DARPP-32), cyclic nucleotide pathways are involved in synaptic transmission, neuron excitability, neuroplasticity and neuroprotection. In this clinical review, we provide an overview of the current clinical status, discuss the general mechanism of action of PDE inhibitors in relation to the corticostriatal and hippocampal circuits and consider several translational challenges. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Dopamine Dynamics and Signaling in Drosophila: An Overview of Genes, Drugs and Behavioral Paradigms

PubMed Central

Yamamoto, Shinya; Seto, Elaine S.

2014-01-01

Changes in dopamine (DA) signaling have been implicated in a number of human neurologic and psychiatric disorders. Similarly, defects in DA signaling in the fruit fly, Drosophila melanogaster, have also been associated with several behavioral defects. As most genes involved in DA synthesis, transport, secretion, and signaling are conserved between species, Drosophila is a powerful genetic model organism to study the regulation of DA signaling in vivo. In this review, we will provide an overview of the genes and drugs that regulate DA biology in Drosophila. Furthermore, we will discuss the behavioral paradigms that are regulated by DA signaling in flies. By analyzing the genes and neuronal circuits that govern such behaviors using sophisticated genetic, pharmacologic, electrophysiologic, and imaging approaches in Drosophila, we will likely gain a better understanding about how this neuromodulator regulates motor tasks and cognition in humans. PMID:24770636

IP3R-mediated Ca2+ release regulates protein metabolism in Drosophila neuroendocrine cells: implications for development under nutrient stress.

PubMed

Megha; Hasan, Gaiti

2017-04-15

Successful completion of animal development is fundamentally reliant on nutritional cues. Surviving periods of nutritional insufficiency requires adaptations that are coordinated, in part, by neural circuits. As neuropeptides secreted by neuroendocrine (NE) cells modulate neural circuits, we investigated NE cell function during development under nutrient stress. Starved Drosophila larvae exhibited reduced pupariation if either insulin signaling or IP 3 /Ca 2+ signaling were downregulated in NE cells. Moreover, an IP 3 R (inositol 1,4,5-trisphosphate receptor) loss-of-function mutant displayed reduced protein synthesis, which was rescued by overexpression of either InR (insulin receptor) or IP 3 R in NE cells of the mutant, suggesting that the two signaling pathways might be functionally compensatory. Furthermore, cultured IP 3 R mutant NE cells, but not neurons, exhibited reduced protein translation. Thus cell-specific regulation of protein synthesis by IP 3 R in NE cells influences protein metabolism. We propose that this regulation helps developing animals survive in poor nutritional conditions. © 2017. Published by The Company of Biologists Ltd.

TGF-β Signaling in Dopaminergic Neurons Regulates Dendritic Growth, Excitatory-Inhibitory Synaptic Balance, and Reversal Learning.

PubMed

Luo, Sarah X; Timbang, Leah; Kim, Jae-Ick; Shang, Yulei; Sandoval, Kadellyn; Tang, Amy A; Whistler, Jennifer L; Ding, Jun B; Huang, Eric J

2016-12-20

Neural circuits involving midbrain dopaminergic (DA) neurons regulate reward and goal-directed behaviors. Although local GABAergic input is known to modulate DA circuits, the mechanism that controls excitatory/inhibitory synaptic balance in DA neurons remains unclear. Here, we show that DA neurons use autocrine transforming growth factor β (TGF-β) signaling to promote the growth of axons and dendrites. Surprisingly, removing TGF-β type II receptor in DA neurons also disrupts the balance in TGF-β1 expression in DA neurons and neighboring GABAergic neurons, which increases inhibitory input, reduces excitatory synaptic input, and alters phasic firing patterns in DA neurons. Mice lacking TGF-β signaling in DA neurons are hyperactive and exhibit inflexibility in relinquishing learned behaviors and re-establishing new stimulus-reward associations. These results support a role for TGF-β in regulating the delicate balance of excitatory/inhibitory synaptic input in local microcircuits involving DA and GABAergic neurons and its potential contributions to neuropsychiatric disorders. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Mapping the functional versatility and fragility of Ras GTPase signaling circuits through in vitro network reconstitution.

PubMed

Coyle, Scott M; Lim, Wendell A

2016-01-14

The Ras-superfamily GTPases are central controllers of cell proliferation and morphology. Ras signaling is mediated by a system of interacting molecules: upstream enzymes (GEF/GAP) regulate Ras's ability to recruit multiple competing downstream effectors. We developed a multiplexed, multi-turnover assay for measuring the dynamic signaling behavior of in vitro reconstituted H-Ras signaling systems. By including both upstream regulators and downstream effectors, we can systematically map how different network configurations shape the dynamic system response. The concentration and identity of both upstream and downstream signaling components strongly impacted the timing, duration, shape, and amplitude of effector outputs. The distorted output of oncogenic alleles of Ras was highly dependent on the balance of positive (GAP) and negative (GEF) regulators in the system. We found that different effectors interpreted the same inputs with distinct output dynamics, enabling a Ras system to encode multiple unique temporal outputs in response to a single input. We also found that different Ras-to-GEF positive feedback mechanisms could reshape output dynamics in distinct ways, such as signal amplification or overshoot minimization. Mapping of the space of output behaviors accessible to Ras provides a design manual for programming Ras circuits, and reveals how these systems are readily adapted to produce an array of dynamic signaling behaviors. Nonetheless, this versatility comes with a trade-off of fragility, as there exist numerous paths to altered signaling behaviors that could cause disease.

49 CFR 212.211 - Apprentice signal and train control inspector.

Code of Federal Regulations, 2010 CFR

2010-10-01

... RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION STATE SAFETY PARTICIPATION REGULATIONS State... to use electrical test equipment in direct current and alternating current circuits; and (2) A basic...

Phase-synchroniser based on gm-C all-pass filter chain with sliding mode control

NASA Astrophysics Data System (ADS)

Mitić, Darko B.; Jovanović, Goran S.; Stojčev, Mile K.; Antić, Dragan S.

2015-03-01

Phase-synchronisers have many applications in VLSI circuit designs. They are used in CMOS RF circuits including phase (de)modulators, phase recovery circuits, multiphase synthesis, etc. In this article, a phase-synchroniser based on gm-C all-pass filter chain with sliding mode control is presented. The filter chain provides good controllable delay characteristics over the full range of phase and frequency regulation, without deterioration of input signal amplitude and waveform, while the sliding mode control enables us to achieve fast and predetermined finite locking time. IHP 0.25 µm SiGe BiCMOS technology has been used in design and verification processes. The circuit operates in the frequency range from 33 MHz up to 150 MHz. Simulation results indicate that it is possible to achieve very fast synchronisation time period, which is approximately four time intervals of the input signal during normal operation, and 20 time intervals during power-on.

The TNF receptor and Ig superfamily members form an integrated signaling circuit controlling dendritic cell homeostasis

PubMed Central

De Trez, Carl; Ware, Carl F.

2008-01-01

Dendritic cells (DC) constitute the most potent antigen presenting cells of the immune system, playing a key role bridging innate and adaptive immune responses. Specialized DC subsets differ depending on their origin, tissue location and the influence of trophic factors, the latter remain to be fully understood. Stromal cell and myeloid-associated Lymphotoxin-β receptor (LTβR) signaling is required for the local proliferation of lymphoid tissue DC. This review focuses the LTβR signaling cascade as a crucial positive trophic signal in the homeostasis of DC subsets. The noncanonical coreceptor pathway comprised of the Immunoglobulin (Ig) superfamily member, B and T lymphocyte attenuator (BTLA) and TNFR superfamily member, Herpesvirus entry mediator (HVEM) counter regulates the trophic signaling by LTβR. Together both pathways form an integrated signaling circuit achieving homeostasis of DC subsets. PMID:18511331

Low-to-Medium Power Single Chip Digital Controlled DC-DC Regulator for Point-of-Load Applications

NASA Technical Reports Server (NTRS)

Adell, Philippe C. (Inventor); Bakkaloglu, Bertan (Inventor); Vermeire, Bert (Inventor); Liu, Tao (Inventor)

2015-01-01

A DC-DC converter for generating a DC output voltage includes: a digitally controlled pulse width modulator (DPWM) for controlling a switching power stage to supply a varying voltage to an inductor; and a digital voltage feedback circuit for controlling the DPWM in accordance with a feedback voltage corresponding to the DC output voltage, the digital voltage feedback circuit including: a first voltage controlled oscillator for converting the feedback voltage into a first frequency signal and to supply the first frequency signal to a first frequency discriminator; a second voltage controlled oscillator for converting a reference voltage into a second frequency signal and to supply the second frequency signal to a second frequency discriminator; a digital comparator for comparing digital outputs of the first and second frequency discriminators and for outputting a digital feedback signal; and a controller for controlling the DPWM in accordance with the digital feedback signal.

How does calcium interact with the cytoskeleton to regulate growth cone motility during axon pathfinding?

PubMed

Gasperini, Robert J; Pavez, Macarena; Thompson, Adrian C; Mitchell, Camilla B; Hardy, Holly; Young, Kaylene M; Chilton, John K; Foa, Lisa

2017-10-01

The precision with which neurons form connections is crucial for the normal development and function of the nervous system. The development of neuronal circuitry in the nervous system is accomplished by axon pathfinding: a process where growth cones guide axons through the embryonic environment to connect with their appropriate synaptic partners to form functional circuits. Despite intense efforts over many years to understand how this process is regulated, the complete repertoire of molecular mechanisms that govern the growth cone cytoskeleton and hence motility, remain unresolved. A central tenet in the axon guidance field is that calcium signals regulate growth cone behaviours such as extension, turning and pausing by regulating rearrangements of the growth cone cytoskeleton. Here, we provide evidence that not only the amplitude of a calcium signal is critical for growth cone motility but also the source of calcium mobilisation. We provide an example of this idea by demonstrating that manipulation of calcium signalling via L-type voltage gated calcium channels can perturb sensory neuron motility towards a source of netrin-1. Understanding how calcium signals can be transduced to initiate cytoskeletal changes represents a significant gap in our current knowledge of the mechanisms that govern axon guidance, and consequently the formation of functional neural circuits in the developing nervous system. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

The Topographical Mapping in Drosophila Central Complex Network and Its Signal Routing

PubMed Central

Chang, Po-Yen; Su, Ta-Shun; Shih, Chi-Tin; Lo, Chung-Chuan

2017-01-01

Neural networks regulate brain functions by routing signals. Therefore, investigating the detailed organization of a neural circuit at the cellular levels is a crucial step toward understanding the neural mechanisms of brain functions. To study how a complicated neural circuit is organized, we analyzed recently published data on the neural circuit of the Drosophila central complex, a brain structure associated with a variety of functions including sensory integration and coordination of locomotion. We discovered that, except for a small number of “atypical” neuron types, the network structure formed by the identified 194 neuron types can be described by only a few simple mathematical rules. Specifically, the topological mapping formed by these neurons can be reconstructed by applying a generation matrix on a small set of initial neurons. By analyzing how information flows propagate with or without the atypical neurons, we found that while the general pattern of signal propagation in the central complex follows the simple topological mapping formed by the “typical” neurons, some atypical neurons can substantially re-route the signal pathways, implying specific roles of these neurons in sensory signal integration. The present study provides insights into the organization principle and signal integration in the central complex. PMID:28443014

Gene regulatory and signaling networks exhibit distinct topological distributions of motifs

NASA Astrophysics Data System (ADS)

Ferreira, Gustavo Rodrigues; Nakaya, Helder Imoto; Costa, Luciano da Fontoura

2018-04-01

The biological processes of cellular decision making and differentiation involve a plethora of signaling pathways and gene regulatory circuits. These networks in turn exhibit a multitude of motifs playing crucial parts in regulating network activity. Here we compare the topological placement of motifs in gene regulatory and signaling networks and observe that it suggests different evolutionary strategies in motif distribution for distinct cellular subnetworks.

Approximate circuits for increased reliability

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

Hamlet, Jason R.; Mayo, Jackson R.

2015-08-18

Embodiments of the invention describe a Boolean circuit having a voter circuit and a plurality of approximate circuits each based, at least in part, on a reference circuit. The approximate circuits are each to generate one or more output signals based on values of received input signals. The voter circuit is to receive the one or more output signals generated by each of the approximate circuits, and is to output one or more signals corresponding to a majority value of the received signals. At least some of the approximate circuits are to generate an output value different than the referencemore » circuit for one or more input signal values; however, for each possible input signal value, the majority values of the one or more output signals generated by the approximate circuits and received by the voter circuit correspond to output signal result values of the reference circuit.« less

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

Hamlet, Jason R.; Mayo, Jackson R.

Embodiments of the invention describe a Boolean circuit having a voter circuit and a plurality of approximate circuits each based, at least in part, on a reference circuit. The approximate circuits are each to generate one or more output signals based on values of received input signals. The voter circuit is to receive the one or more output signals generated by each of the approximate circuits, and is to output one or more signals corresponding to a majority value of the received signals. At least some of the approximate circuits are to generate an output value different than the referencemore » circuit for one or more input signal values; however, for each possible input signal value, the majority values of the one or more output signals generated by the approximate circuits and received by the voter circuit correspond to output signal result values of the reference circuit.« less

Robustness, evolvability, and the logic of genetic regulation.

PubMed

Payne, Joshua L; Moore, Jason H; Wagner, Andreas

2014-01-01

In gene regulatory circuits, the expression of individual genes is commonly modulated by a set of regulating gene products, which bind to a gene's cis-regulatory region. This region encodes an input-output function, referred to as signal-integration logic, that maps a specific combination of regulatory signals (inputs) to a particular expression state (output) of a gene. The space of all possible signal-integration functions is vast and the mapping from input to output is many-to-one: For the same set of inputs, many functions (genotypes) yield the same expression output (phenotype). Here, we exhaustively enumerate the set of signal-integration functions that yield identical gene expression patterns within a computational model of gene regulatory circuits. Our goal is to characterize the relationship between robustness and evolvability in the signal-integration space of regulatory circuits, and to understand how these properties vary between the genotypic and phenotypic scales. Among other results, we find that the distributions of genotypic robustness are skewed, so that the majority of signal-integration functions are robust to perturbation. We show that the connected set of genotypes that make up a given phenotype are constrained to specific regions of the space of all possible signal-integration functions, but that as the distance between genotypes increases, so does their capacity for unique innovations. In addition, we find that robust phenotypes are (i) evolvable, (ii) easily identified by random mutation, and (iii) mutationally biased toward other robust phenotypes. We explore the implications of these latter observations for mutation-based evolution by conducting random walks between randomly chosen source and target phenotypes. We demonstrate that the time required to identify the target phenotype is independent of the properties of the source phenotype.

Robustness, Evolvability, and the Logic of Genetic Regulation

PubMed Central

Moore, Jason H.; Wagner, Andreas

2014-01-01

In gene regulatory circuits, the expression of individual genes is commonly modulated by a set of regulating gene products, which bind to a gene’s cis-regulatory region. This region encodes an input-output function, referred to as signal-integration logic, that maps a specific combination of regulatory signals (inputs) to a particular expression state (output) of a gene. The space of all possible signal-integration functions is vast and the mapping from input to output is many-to-one: for the same set of inputs, many functions (genotypes) yield the same expression output (phenotype). Here, we exhaustively enumerate the set of signal-integration functions that yield idential gene expression patterns within a computational model of gene regulatory circuits. Our goal is to characterize the relationship between robustness and evolvability in the signal-integration space of regulatory circuits, and to understand how these properties vary between the genotypic and phenotypic scales. Among other results, we find that the distributions of genotypic robustness are skewed, such that the majority of signal-integration functions are robust to perturbation. We show that the connected set of genotypes that make up a given phenotype are constrained to specific regions of the space of all possible signal-integration functions, but that as the distance between genotypes increases, so does their capacity for unique innovations. In addition, we find that robust phenotypes are (i) evolvable, (ii) easily identified by random mutation, and (iii) mutationally biased toward other robust phenotypes. We explore the implications of these latter observations for mutation-based evolution by conducting random walks between randomly chosen source and target phenotypes. We demonstrate that the time required to identify the target phenotype is independent of the properties of the source phenotype. PMID:23373974

SYNTHETIC BIOLOGY. Emergent genetic oscillations in a synthetic microbial consortium.

PubMed

Chen, Ye; Kim, Jae Kyoung; Hirning, Andrew J; Josić, Krešimir; Bennett, Matthew R

2015-08-28

A challenge of synthetic biology is the creation of cooperative microbial systems that exhibit population-level behaviors. Such systems use cellular signaling mechanisms to regulate gene expression across multiple cell types. We describe the construction of a synthetic microbial consortium consisting of two distinct cell types—an "activator" strain and a "repressor" strain. These strains produced two orthogonal cell-signaling molecules that regulate gene expression within a synthetic circuit spanning both strains. The two strains generated emergent, population-level oscillations only when cultured together. Certain network topologies of the two-strain circuit were better at maintaining robust oscillations than others. The ability to program population-level dynamics through the genetic engineering of multiple cooperative strains points the way toward engineering complex synthetic tissues and organs with multiple cell types. Copyright © 2015, American Association for the Advancement of Science.

Neuropilins are positive regulators of Hedgehog signal transduction

PubMed Central

Hillman, R. Tyler; Feng, Brian Y.; Ni, Jun; Woo, Wei-Meng; Milenkovic, Ljiljana; Hayden Gephart, Melanie G.; Teruel, Mary N.; Oro, Anthony E.; Chen, James K.; Scott, Matthew P.

2011-01-01

The Hedgehog (Hh) pathway is essential for vertebrate embryogenesis, and excessive Hh target gene activation can cause cancer in humans. Here we show that Neuropilin 1 (Nrp1) and Nrp2, transmembrane proteins with roles in axon guidance and vascular endothelial growth factor (VEGF) signaling, are important positive regulators of Hh signal transduction. Nrps are expressed at times and locations of active Hh signal transduction during mouse development. Using cell lines lacking key Hh pathway components, we show that Nrps mediate Hh transduction between activated Smoothened (Smo) protein and the negative regulator Suppressor of Fused (SuFu). Nrp1 transcription is induced by Hh signaling, and Nrp1 overexpression increases maximal Hh target gene activation, indicating the existence of a positive feedback circuit. The regulation of Hh signal transduction by Nrps is conserved between mammals and bony fish, as we show that morpholinos targeting the Nrp zebrafish ortholog nrp1a produce a specific and highly penetrant Hh pathway loss-of-function phenotype. These findings enhance our knowledge of Hh pathway regulation and provide evidence for a conserved nexus between Nrps and this important developmental signaling system. PMID:22051878

Mapping the functional versatility and fragility of Ras GTPase signaling circuits through in vitro network reconstitution

PubMed Central

Coyle, Scott M; Lim, Wendell A

2016-01-01

The Ras-superfamily GTPases are central controllers of cell proliferation and morphology. Ras signaling is mediated by a system of interacting molecules: upstream enzymes (GEF/GAP) regulate Ras’s ability to recruit multiple competing downstream effectors. We developed a multiplexed, multi-turnover assay for measuring the dynamic signaling behavior of in vitro reconstituted H-Ras signaling systems. By including both upstream regulators and downstream effectors, we can systematically map how different network configurations shape the dynamic system response. The concentration and identity of both upstream and downstream signaling components strongly impacted the timing, duration, shape, and amplitude of effector outputs. The distorted output of oncogenic alleles of Ras was highly dependent on the balance of positive (GAP) and negative (GEF) regulators in the system. We found that different effectors interpreted the same inputs with distinct output dynamics, enabling a Ras system to encode multiple unique temporal outputs in response to a single input. We also found that different Ras-to-GEF positive feedback mechanisms could reshape output dynamics in distinct ways, such as signal amplification or overshoot minimization. Mapping of the space of output behaviors accessible to Ras provides a design manual for programming Ras circuits, and reveals how these systems are readily adapted to produce an array of dynamic signaling behaviors. Nonetheless, this versatility comes with a trade-off of fragility, as there exist numerous paths to altered signaling behaviors that could cause disease. DOI: http://dx.doi.org/10.7554/eLife.12435.001 PMID:26765565

Dissection of neuronal gap junction circuits that regulate social behavior in Caenorhabditis elegans.

PubMed

Jang, Heeun; Levy, Sagi; Flavell, Steven W; Mende, Fanny; Latham, Richard; Zimmer, Manuel; Bargmann, Cornelia I

2017-02-14

A hub-and-spoke circuit of neurons connected by gap junctions controls aggregation behavior and related behavioral responses to oxygen, pheromones, and food in Caenorhabditis elegans The molecular composition of the gap junctions connecting RMG hub neurons with sensory spoke neurons is unknown. We show here that the innexin gene unc-9 is required in RMG hub neurons to drive aggregation and related behaviors, indicating that UNC-9-containing gap junctions mediate RMG signaling. To dissect the circuit in detail, we developed methods to inhibit unc-9 -based gap junctions with dominant-negative unc-1 transgenes. unc-1(dn) alters a stomatin-like protein that regulates unc-9 electrical signaling; its disruptive effects can be rescued by a constitutively active UNC-9::GFP protein, demonstrating specificity. Expression of unc-1(dn) in RMG hub neurons, ADL or ASK pheromone-sensing neurons, or URX oxygen-sensing neurons disrupts specific elements of aggregation-related behaviors. In ADL, unc-1(dn) has effects opposite to those of tetanus toxin light chain, separating the roles of ADL electrical and chemical synapses. These results reveal roles of gap junctions in a complex behavior at cellular resolution and provide a tool for similar exploration of other gap junction circuits.

Dissection of neuronal gap junction circuits that regulate social behavior in Caenorhabditis elegans

PubMed Central

Jang, Heeun; Levy, Sagi; Flavell, Steven W.; Mende, Fanny; Latham, Richard; Zimmer, Manuel; Bargmann, Cornelia I.

2017-01-01

A hub-and-spoke circuit of neurons connected by gap junctions controls aggregation behavior and related behavioral responses to oxygen, pheromones, and food in Caenorhabditis elegans. The molecular composition of the gap junctions connecting RMG hub neurons with sensory spoke neurons is unknown. We show here that the innexin gene unc-9 is required in RMG hub neurons to drive aggregation and related behaviors, indicating that UNC-9–containing gap junctions mediate RMG signaling. To dissect the circuit in detail, we developed methods to inhibit unc-9–based gap junctions with dominant-negative unc-1 transgenes. unc-1(dn) alters a stomatin-like protein that regulates unc-9 electrical signaling; its disruptive effects can be rescued by a constitutively active UNC-9::GFP protein, demonstrating specificity. Expression of unc-1(dn) in RMG hub neurons, ADL or ASK pheromone-sensing neurons, or URX oxygen-sensing neurons disrupts specific elements of aggregation-related behaviors. In ADL, unc-1(dn) has effects opposite to those of tetanus toxin light chain, separating the roles of ADL electrical and chemical synapses. These results reveal roles of gap junctions in a complex behavior at cellular resolution and provide a tool for similar exploration of other gap junction circuits. PMID:28143932

Circuit Design Features of a Stable Two-Cell System.

PubMed

Zhou, Xu; Franklin, Ruth A; Adler, Miri; Jacox, Jeremy B; Bailis, Will; Shyer, Justin A; Flavell, Richard A; Mayo, Avi; Alon, Uri; Medzhitov, Ruslan

2018-02-08

Cell communication within tissues is mediated by multiple paracrine signals including growth factors, which control cell survival and proliferation. Cells and the growth factors they produce and receive constitute a circuit with specific properties that ensure homeostasis. Here, we used computational and experimental approaches to characterize the features of cell circuits based on growth factor exchange between macrophages and fibroblasts, two cell types found in most mammalian tissues. We found that the macrophage-fibroblast cell circuit is stable and robust to perturbations. Analytical screening of all possible two-cell circuit topologies revealed the circuit features sufficient for stability, including environmental constraint and negative-feedback regulation. Moreover, we found that cell-cell contact is essential for the stability of the macrophage-fibroblast circuit. These findings illustrate principles of cell circuit design and provide a quantitative perspective on cell interactions. Copyright © 2018 Elsevier Inc. All rights reserved.

Biological Signal Processing with a Genetic Toggle Switch

PubMed Central

Hillenbrand, Patrick; Fritz, Georg; Gerland, Ulrich

2013-01-01

Complex gene regulation requires responses that depend not only on the current levels of input signals but also on signals received in the past. In digital electronics, logic circuits with this property are referred to as sequential logic, in contrast to the simpler combinatorial logic without such internal memory. In molecular biology, memory is implemented in various forms such as biochemical modification of proteins or multistable gene circuits, but the design of the regulatory interface, which processes the input signals and the memory content, is often not well understood. Here, we explore design constraints for such regulatory interfaces using coarse-grained nonlinear models and stochastic simulations of detailed biochemical reaction networks. We test different designs for biological analogs of the most versatile memory element in digital electronics, the JK-latch. Our analysis shows that simple protein-protein interactions and protein-DNA binding are sufficient, in principle, to implement genetic circuits with the capabilities of a JK-latch. However, it also exposes fundamental limitations to its reliability, due to the fact that biological signal processing is asynchronous, in contrast to most digital electronics systems that feature a central clock to orchestrate the timing of all operations. We describe a seemingly natural way to improve the reliability by invoking the master-slave concept from digital electronics design. This concept could be useful to interpret the design of natural regulatory circuits, and for the design of synthetic biological systems. PMID:23874595

Alterations of GABAergic Signaling in Autism Spectrum Disorders

PubMed Central

Pizzarelli, Rocco; Cherubini, Enrico

2011-01-01

Autism spectrum disorders (ASDs) comprise a heterogeneous group of pathological conditions, mainly of genetic origin, characterized by stereotyped behavior, marked impairment in verbal and nonverbal communication, social skills, and cognition. Interestingly, in a small number of cases, ASDs are associated with single mutations in genes encoding for neuroligin-neurexin families. These are adhesion molecules which, by regulating transsynaptic signaling, contribute to maintain a proper excitatory/inhibitory (E/I) balance at the network level. Furthermore, GABA, the main inhibitory neurotransmitter in adult life, at late embryonic/early postnatal stages has been shown to depolarize and excite targeted cell through an outwardly directed flux of chloride. The depolarizing action of GABA and associated calcium influx regulate a variety of developmental processes from cell migration and differentiation to synapse formation. Here, we summarize recent data concerning the functional role of GABA in building up and refining neuronal circuits early in development and the molecular mechanisms regulating the E/I balance. A dysfunction of the GABAergic signaling early in development leads to a severe E/I unbalance in neuronal circuits, a condition that may account for some of the behavioral deficits observed in ASD patients. PMID:21766041

Integrated mixed signal control IC for 500-kHz switching frequency buck regulator

NASA Astrophysics Data System (ADS)

Chen, Keng; Zhang, Hong

2015-12-01

The main purpose for this work is to study the challenges of designing a digital buck regulator using pipelined analog to digital converter (ADC). Although pipelined ADC can achieve high sampling speed, it will introduce additional phase lag to the buck circuit. Along with the latency brought by processing time of additional digital circuits, as well as the time delay associated with the switching frequency, the closed loop will be unstable; moreover, raw ADC outputs have low signal-to-noise ratio, which usually need back-end calibration. In order to compensate these phase lag and make control loop unconditional stable, as well as boost up signal-to-noise ratio of the ADC block with cost-efficient design, a finite impulse response filter followed by digital proportional-integral-derivative blocks were designed. All these digital function blocks were optimised with processing speed. In the system simulation, it can be found that this controller achieved output regulation within 10% of nominal 5 V output voltage under 1 A/µs load transient condition; moreover, with the soft-start method, there is no turn-on overshooting. The die size of this controller is controlled within 3 mm2 by using 180 nm CMOS technology.

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

Sadowski, Greg

In one form, a logic circuit includes an asynchronous logic circuit, a synchronous logic circuit, and an interface circuit coupled between the asynchronous logic circuit and the synchronous logic circuit. The asynchronous logic circuit has a plurality of asynchronous outputs for providing a corresponding plurality of asynchronous signals. The synchronous logic circuit has a plurality of synchronous inputs corresponding to the plurality of asynchronous outputs, a stretch input for receiving a stretch signal, and a clock output for providing a clock signal. The synchronous logic circuit provides the clock signal as a periodic signal but prolongs a predetermined state ofmore » the clock signal while the stretch signal is active. The asynchronous interface detects whether metastability could occur when latching any of the plurality of the asynchronous outputs of the asynchronous logic circuit using said clock signal, and activates the stretch signal while the metastability could occur.« less

Synthetic biology in mammalian cells: Next generation research tools and therapeutics

PubMed Central

Lienert, Florian; Lohmueller, Jason J; Garg, Abhishek; Silver, Pamela A

2014-01-01

Recent progress in DNA manipulation and gene circuit engineering has greatly improved our ability to programme and probe mammalian cell behaviour. These advances have led to a new generation of synthetic biology research tools and potential therapeutic applications. Programmable DNA-binding domains and RNA regulators are leading to unprecedented control of gene expression and elucidation of gene function. Rebuilding complex biological circuits such as T cell receptor signalling in isolation from their natural context has deepened our understanding of network motifs and signalling pathways. Synthetic biology is also leading to innovative therapeutic interventions based on cell-based therapies, protein drugs, vaccines and gene therapies. PMID:24434884

Feeding State, Insulin and NPR-1 Modulate Chemoreceptor Gene Expression via Integration of Sensory and Circuit Inputs

PubMed Central

Gruner, Matthew; Nelson, Dru; Winbush, Ari; Hintz, Rebecca; Ryu, Leesun; Chung, Samuel H.; Kim, Kyuhyung; Gabel, Chrisopher V.; van der Linden, Alexander M.

2014-01-01

Feeding state and food availability can dramatically alter an animals' sensory response to chemicals in its environment. Dynamic changes in the expression of chemoreceptor genes may underlie some of these food and state-dependent changes in chemosensory behavior, but the mechanisms underlying these expression changes are unknown. Here, we identified a KIN-29 (SIK)-dependent chemoreceptor, srh-234, in C. elegans whose expression in the ADL sensory neuron type is regulated by integration of sensory and internal feeding state signals. We show that in addition to KIN-29, signaling is mediated by the DAF-2 insulin-like receptor, OCR-2 TRPV channel, and NPR-1 neuropeptide receptor. Cell-specific rescue experiments suggest that DAF-2 and OCR-2 act in ADL, while NPR-1 acts in the RMG interneurons. NPR-1-mediated regulation of srh-234 is dependent on gap-junctions, implying that circuit inputs regulate the expression of chemoreceptor genes in sensory neurons. Using physical and genetic manipulation of ADL neurons, we show that sensory inputs from food presence and ADL neural output regulate srh-234 expression. While KIN-29 and DAF-2 act primarily via the MEF-2 (MEF2) and DAF-16 (FOXO) transcription factors to regulate srh-234 expression in ADL neurons, OCR-2 and NPR-1 likely act via a calcium-dependent but MEF-2- and DAF-16-independent pathway. Together, our results suggest that sensory- and circuit-mediated regulation of chemoreceptor genes via multiple pathways may allow animals to precisely regulate and fine-tune their chemosensory responses as a function of internal and external conditions. PMID:25357003

Neuropeptide Signaling Networks and Brain Circuit Plasticity.

PubMed

McClard, Cynthia K; Arenkiel, Benjamin R

2018-01-01

The brain is a remarkable network of circuits dedicated to sensory integration, perception, and response. The computational power of the brain is estimated to dwarf that of most modern supercomputers, but perhaps its most fascinating capability is to structurally refine itself in response to experience. In the language of computers, the brain is loaded with programs that encode when and how to alter its own hardware. This programmed "plasticity" is a critical mechanism by which the brain shapes behavior to adapt to changing environments. The expansive array of molecular commands that help execute this programming is beginning to emerge. Notably, several neuropeptide transmitters, previously best characterized for their roles in hypothalamic endocrine regulation, have increasingly been recognized for mediating activity-dependent refinement of local brain circuits. Here, we discuss recent discoveries that reveal how local signaling by corticotropin-releasing hormone reshapes mouse olfactory bulb circuits in response to activity and further explore how other local neuropeptide networks may function toward similar ends.

PDF-1 neuropeptide signaling modulates a neural circuit for mate-searching behavior in C. elegans.

PubMed

Barrios, Arantza; Ghosh, Rajarshi; Fang, Chunhui; Emmons, Scott W; Barr, Maureen M

2012-12-01

Appetitive behaviors require complex decision making that involves the integration of environmental stimuli and physiological needs. C. elegans mate searching is a male-specific exploratory behavior regulated by two competing needs: food and reproductive appetite. We found that the pigment dispersing factor receptor (PDFR-1) modulates the circuit that encodes the male reproductive drive that promotes male exploration following mate deprivation. PDFR-1 and its ligand, PDF-1, stimulated mate searching in the male, but not in the hermaphrodite. pdf-1 was required in the gender-shared interneuron AIM, and the receptor acted in internal and external environment-sensing neurons of the shared nervous system (URY, PQR and PHA) to produce mate-searching behavior. Thus, the pdf-1 and pdfr-1 pathway functions in non-sex-specific neurons to produce a male-specific, goal-oriented exploratory behavior. Our results indicate that secretin neuropeptidergic signaling is involved in regulating motivational internal states.

From Anxious to Reckless: A Control Systems Approach Unifies Prefrontal-Limbic Regulation Across the Spectrum of Threat Detection.

PubMed

Mujica-Parodi, Lilianne R; Cha, Jiook; Gao, Jonathan

2017-01-01

Here we provide an integrative review of basic control circuits, and introduce techniques by which their regulation can be quantitatively measured using human neuroimaging. We illustrate the utility of the control systems approach using four human neuroimaging threat detection studies ( N = 226), to which we applied circuit-wide analyses in order to identify the key mechanism underlying individual variation. In so doing, we build upon the canonical prefrontal-limbic control system to integrate circuit-wide influence from the inferior frontal gyrus (IFG). These were incorporated into a computational control systems model constrained by neuroanatomy and designed to replicate our experimental data. In this model, the IFG acts as an informational set point, gating signals between the primary prefrontal-limbic negative feedback loop and its cortical information-gathering loop. Along the cortical route, if the sensory cortex provides sufficient information to make a threat assessment, the signal passes to the ventromedial prefrontal cortex (vmPFC), whose threat-detection threshold subsequently modulates amygdala outputs. However, if signal outputs from the sensory cortex do not provide sufficient information during the first pass, the signal loops back to the sensory cortex, with each cycle providing increasingly fine-grained processing of sensory data. Simulations replicate IFG (chaotic) dynamics experimentally observed at both ends at the threat-detection spectrum. As such, they identify distinct types of IFG disconnection from the circuit, with associated clinical outcomes. If IFG thresholds are too high, the IFG and sensory cortex cycle for too long; in the meantime the coarse-grained (excitatory) pathway will dominate, biasing ambiguous stimuli as false positives. On the other hand, if cortical IFG thresholds are too low, the inhibitory pathway will suppress the amygdala without cycling back to the sensory cortex for much-needed fine-grained sensory cortical data, biasing ambiguous stimuli as false negatives. Thus, the control systems model provides a consistent mechanism for IFG regulation, capable of producing results consistent with our data for the full spectrum of threat-detection: from fearful to optimal to reckless. More generally, it illustrates how quantitative characterization of circuit dynamics can be used to unify a fundamental dimension across psychiatric affective symptoms, with implications for populations that range from anxiety disorders to addiction.

Measuring circuit

DOEpatents

Sun, Shan C.; Chaprnka, Anthony G.

1977-01-11

An automatic gain control circuit functions to adjust the magnitude of an input signal supplied to a measuring circuit to a level within the dynamic range of the measuring circuit while a log-ratio circuit adjusts the magnitude of the output signal from the measuring circuit to the level of the input signal and optimizes the signal-to-noise ratio performance of the measuring circuit.

MicroRNA-mediated regulatory circuits: outlook and perspectives

NASA Astrophysics Data System (ADS)

Cora', Davide; Re, Angela; Caselle, Michele; Bussolino, Federico

2017-08-01

MicroRNAs have been found to be necessary for regulating genes implicated in almost all signaling pathways, and consequently their dysfunction influences many diseases, including cancer. Understanding of the complexity of the microRNA-mediated regulatory network has grown in terms of size, connectivity and dynamics with the development of computational and, more recently, experimental high-throughput approaches for microRNA target identification. Newly developed studies on recurrent microRNA-mediated circuits in regulatory networks, also known as network motifs, have substantially contributed to addressing this complexity, and therefore to helping understand the ways by which microRNAs achieve their regulatory role. This review provides a summarizing view of the state-of-the-art, and perspectives of research efforts on microRNA-mediated regulatory motifs. In this review, we discuss the topological properties characterizing different types of circuits, and the regulatory features theoretically enabled by such properties, with a special emphasis on examples of circuits typifying their biological significance in experimentally validated contexts. Finally, we will consider possible future developments, in particular regarding microRNA-mediated circuits involving long non-coding RNAs and epigenetic regulators.

GABA-CREB signalling regulates maturation and survival of newly generated neurons in the adult hippocampus

PubMed Central

Jagasia, Ravi; Steib, Kathrin; Englberger, Elisabeth; Herold, Sabine; Faus-Kessler, Theresa; Saxe, Michael; Gage, Fred H.; Song, Hongjun; Lie, D. Chichung

2009-01-01

Survival and integration of new neurons in the hippocampal circuit are rate-limiting steps in adult hippocampal neurogenesis. Neuronal network activity is a major regulator of these processes, yet little is known about the respective downstream signalling pathways. Here, we investigate the role of CREB signalling in adult hippocampal neurogenesis. CREB is activated in new granule neurons during a distinct developmental period. Loss of CREB function in a cell-autonomous fashion impairs dendritic development, decreases the expression of the neurogenic transcription factor NeuroD and of the neuronal microtubule associated protein, DCX, and compromises the survival of newborn neurons. In addition, GABA-mediated excitation regulates CREB activation at early developmental stages. Importantly, developmental defects following loss of GABA-mediated excitation can be compensated by enhanced CREB signalling. These results indicate that CREB signalling is a central pathway in adult hippocampal neurogenesis, regulating the development and survival of new hippocampal neurons downstream of GABA-mediated excitation. PMID:19553437

Neuroendocrine circuits governing energy balance and stress regulation: functional overlap and therapeutic implications

PubMed Central

Ulrich-Lai, Yvonne M.; Ryan, Karen K.

2014-01-01

Significant co-morbidities between obesity-related metabolic disease and stress-related psychological disorders suggest important functional interactions between energy balance and brain stress integration. Largely overlapping neural circuits control these systems, and this anatomical arrangement optimizes opportunities for mutual influence. Here we first review the current literature identifying effects of metabolic neuroendocrine signals on stress regulation, and vice versa. Next, the contributions of reward driven food intake to these metabolic and stress interactions are discussed. Lastly, we consider the inter-relationships among metabolism, stress and reward in light of their important implications in the development of therapies for metabolism- or stress-related disease. PMID:24630812

Autonomous and nonautonomous regulation of axis formation by antagonistic signaling via 7-span cAMP receptors and GSK3 in Dictyostelium.

PubMed

Ginsburg, G T; Kimmel, A R

1997-08-15

Early during Dictyostelium development a fundamental cell-fate decision establishes the anteroposterior (prestalk/prespore) axis. Signaling via the 7-transmembrane cAMP receptor CAR4 is essential for creating and maintaining a normal pattern; car4-null alleles have decreased levels of prestalk-specific mRNAs but enhanced expression of prespore genes. car4- cells produce all of the signals required for prestalk differentiation but lack an extracellular factor necessary for prespore differentiation of wild-type cells. This secreted factor decreases the sensitivity of prespore cells to inhibition by the prestalk morphogen DIF-1. At the cell autonomous level, CAR4 is linked to intracellular circuits that activate prestalk but inhibit prespore differentiation. The autonomous action of CAR4 is antagonistic to the positive intracellular signals mediated by another cAMP receptor, CAR1 and/or CAR3. Additional data indicate that these CAR-mediated pathways converge at the serine/threonine protein kinase GSK3, suggesting that the anterior (prestalk)/posterior (prespore) axis of Dictyostelium is regulated by an ancient mechanism that is shared by the Wnt/Fz circuits for dorsoventral patterning during early Xenopus development and establishing Drosophila segment polarity.

Central genes, pathways and modules that regulate bone mass.

PubMed

Quiros-Gonzalez, Isabel; Yadav, Vijay K

2014-11-01

Bones are structures that give the shape and defined features to vertebrates, protect several soft organs and perform multiple endocrine influences on other organs. To achieve these functions bones are first modeled early during life and then constantly remodeled throughout life. The process of bone (re)modeling happens simultaneously at multitude of locations in the skeleton and ensures that vertebrates have a mechanically strong yet a flexible skeleton to the most part of their life. Given the extent of its occurrence in the body, bone remodeling is a highly energy demanding process and is co-ordinated with other physiological processes as diverse as energy metabolism, sleep-wake cycle and reproduction. Neuronal circuits in the brain play a very important role in the coordination of bone remodeling with other organ system functions, and perform this function in sync with environmental and peripheral hormonal cues. In this review, we will focus on the roles of hormonal signals and neural circuits that originate in, or impinge on, the brain in the regulation of bone mass. We will provide herein an updated view of how advances in molecular genetics have refined the neural circuits involved in the regulation of bone mass, from the whole brain level to the specific neuronal populations and their neurotransmitters. This will help to understand the mechanisms whereby vertebrate brain regulates bone mass by fine-tuning metabolic signals that originate in the brain or elsewhere in the body. Copyright © 2014 Elsevier Inc. All rights reserved.

High voltage DC power supply

DOEpatents

Droege, T.F.

1989-12-19

A high voltage DC power supply having a first series resistor at the output for limiting current in the event of a short-circuited output, a second series resistor for sensing the magnitude of output current, and a voltage divider circuit for providing a source of feedback voltage for use in voltage regulation is disclosed. The voltage divider circuit is coupled to the second series resistor so as to compensate the feedback voltage for a voltage drop across the first series resistor. The power supply also includes a pulse-width modulated control circuit, having dual clock signals, which is responsive to both the feedback voltage and a command voltage, and also includes voltage and current measuring circuits responsive to the feedback voltage and the voltage developed across the second series resistor respectively. 7 figs.

High voltage DC power supply

DOEpatents

Droege, Thomas F.

1989-01-01

A high voltage DC power supply having a first series resistor at the output for limiting current in the event of a short-circuited output, a second series resistor for sensing the magnitude of output current, and a voltage divider circuit for providing a source of feedback voltage for use in voltage regulation is disclosed. The voltage divider circuit is coupled to the second series resistor so as to compensate the feedback voltage for a voltage drop across the first series resistor. The power supply also includes a pulse-width modulated control circuit, having dual clock signals, which is responsive to both the feedback voltage and a command voltage, and also includes voltage and current measuring circuits responsive to the feedback voltage and the voltage developed across the second series resistor respectively.

Insights into Rapid Modulation of Neuroplasticity by Brain Estrogens

PubMed Central

Woolfrey, Kevin M.; Penzes, Peter

2013-01-01

Converging evidence from cellular, electrophysiological, anatomic, and behavioral studies suggests that the remodeling of synapse structure and function is a critical component of cognition. This modulation of neuroplasticity can be achieved through the actions of numerous extracellular signals. Moreover, it is thought that it is the integration of different extracellular signals regulation of neuroplasticity that greatly influences cognitive function. One group of signals that exerts powerful effects on multiple neurologic processes is estrogens. Classically, estrogens have been described to exert their effects over a period of hours to days. However, there is now increasing evidence that estrogens can rapidly influence multiple behaviors, including those that require forebrain neural circuitry. Moreover, these effects are found in both sexes. Critically, it is now emerging that the modulation of cognition by rapid estrogenic signaling is achieved by activation of specific signaling cascades and regulation of synapse structure and function, cumulating in the rewiring of neural circuits. The importance of understanding the rapid effects of estrogens on forebrain function and circuitry is further emphasized as investigations continue to consider the potential of estrogenic-based therapies for neuropathologies. This review focuses on how estrogens can rapidly influence cognition and the emerging mechanisms that underlie these effects. We discuss the potential sources and the biosynthesis of estrogens within the brain and the consequences of rapid estrogenic-signaling on the remodeling of neural circuits. Furthermore, we argue that estrogens act via distinct signaling pathways to modulate synapse structure and function in a manner that may vary with cell type, developmental stage, and sex. Finally, we present a model in which the coordination of rapid estrogenic-signaling and activity-dependent stimuli can result in long-lasting changes in neural circuits, contributing to cognition, with potential relevance for the development of novel estrogenic-based therapies for neurodevelopmental or neurodegenerative disorders. PMID:24076546

Feeding status and serotonin rapidly and reversibly modulate a Caenorhabditis elegans chemosensory circuit

PubMed Central

Chao, Michael Y.; Komatsu, Hidetoshi; Fukuto, Hana S.; Dionne, Heather M.; Hart, Anne C.

2004-01-01

Serotonin (5-HT) modulates synaptic efficacy in the nervous system of vertebrates and invertebrates. In the nematode Caenorhabditis elegans, many behaviors are regulated by 5-HT levels, which are in turn regulated by the presence or absence of food. Here, we show that both food and 5-HT signaling modulate chemosensory avoidance response of octanol in C. elegans, and that this modulation is both rapid and reversible. Sensitivity to octanol is decreased when animals are off food or when 5-HT levels are decreased; conversely, sensitivity is increased when animals are on food or have increased 5-HT signaling. Laser microsurgery and behavioral experiments reveal that sensory input from different subsets of octanol-sensing neurons is selectively used, depending on stimulus strength, feeding status, and 5-HT levels. 5-HT directly targets at least one pair of sensory neurons, and 5-HT signaling requires the Gα protein GPA-11. Glutamatergic signaling is required for response to octanol, and the GLR-1 glutamate receptor plays an important role in behavioral response off food but not on food. Our results demonstrate that 5-HT modulation of neuronal activity via G protein signaling underlies behavioral plasticity by rapidly altering the functional circuitry of a chemosensory circuit. PMID:15492222

Evolution and Design Governing Signal Precision and Amplification in a Bacterial Chemosensory Pathway

PubMed Central

Espinosa, Leon; Baronian, Grégory; Molle, Virginie; Mauriello, Emilia M. F.; Brochier-Armanet, Céline; Mignot, Tâm

2015-01-01

Understanding the principles underlying the plasticity of signal transduction networks is fundamental to decipher the functioning of living cells. In Myxococcus xanthus, a particular chemosensory system (Frz) coordinates the activity of two separate motility systems (the A- and S-motility systems), promoting multicellular development. This unusual structure asks how signal is transduced in a branched signal transduction pathway. Using combined evolution-guided and single cell approaches, we successfully uncoupled the regulations and showed that the A-motility regulation system branched-off an existing signaling system that initially only controlled S-motility. Pathway branching emerged in part following a gene duplication event and changes in the circuit structure increasing the signaling efficiency. In the evolved pathway, the Frz histidine kinase generates a steep biphasic response to increasing external stimulations, which is essential for signal partitioning to the motility systems. We further show that this behavior results from the action of two accessory response regulator proteins that act independently to filter and amplify signals from the upstream kinase. Thus, signal amplification loops may underlie the emergence of new connectivity in signal transduction pathways. PMID:26291327

Cell-autonomous inactivation of the Reelin pathway impairs adult neurogenesis in the hippocampus

PubMed Central

Teixeira, Catia M.; Kron, Michelle M.; Masachs, Nuria; Zhang, Helen; Lagace, Diane C.; Martinez, Albert; Reillo, Isabel; Duan, Xin; Bosch, Carles; Pujadas, Lluis; Brunso, Lucas; Song, Hongjun; Eisch, Amelia J.; Borrell, Victor; Howell, Brian W.; Parent, Jack M.; Soriano, Eduardo

2012-01-01

Adult hippocampal neurogenesis is thought to be essential for learning and memory and has been implicated in the pathogenesis of several disorders. Although recent studies have identified key factors regulating neuroprogenitor proliferation in the adult hippocampus, the mechanisms that control the migration and integration of adult-born neurons into circuits are largely unknown. Reelin is an extracellular matrix protein that is vital for neuronal development. Activation of the Reelin cascade leads to phosphorylation of disabled-1 (Dab1), an adaptor protein required for Reelin signaling. Here we used transgenic mouse and retroviral reporters along with Reelin signaling gain- and loss-of-function studies to show that the Reelin pathway regulates migration and dendritic development of adult-generated hippocampal neurons. Whereas overexpression of Reelin accelerated dendritic maturation, inactivation of the Reelin signaling pathway specifically in adult neuroprogenitor cells resulted in aberrant migration, decreased dendrite development, formation of ectopic dendrites in the hilus and the establishment of aberrant circuits. Our findings support a cell-autonomous and critical role for the Reelin pathway in regulating dendritic development and the integration of adult-generated granule cells and point to this pathway as a key regulator of adult neurogenesis. Moreover, our data reveal a novel role of the Reelin cascade in adult brain function with potential implications for the pathogenesis of several neurological and psychiatric disorders. PMID:22933789

How MAP kinase modules function as robust, yet adaptable, circuits.

PubMed

Tian, Tianhai; Harding, Angus

2014-01-01

Genetic and biochemical studies have revealed that the diversity of cell types and developmental patterns evident within the animal kingdom is generated by a handful of conserved, core modules. Core biological modules must be robust, able to maintain functionality despite perturbations, and yet sufficiently adaptable for random mutations to generate phenotypic variation during evolution. Understanding how robust, adaptable modules have influenced the evolution of eukaryotes will inform both evolutionary and synthetic biology. One such system is the MAP kinase module, which consists of a 3-tiered kinase circuit configuration that has been evolutionarily conserved from yeast to man. MAP kinase signal transduction pathways are used across eukaryotic phyla to drive biological functions that are crucial for life. Here we ask the fundamental question, why do MAPK modules follow a conserved 3-tiered topology rather than some other number? Using computational simulations, we identify a fundamental 2-tiered circuit topology that can be readily reconfigured by feedback loops and scaffolds to generate diverse signal outputs. When this 2-kinase circuit is connected to proximal input kinases, a 3-tiered modular configuration is created that is both robust and adaptable, providing a biological circuit that can regulate multiple phenotypes and maintain functionality in an uncertain world. We propose that the 3-tiered signal transduction module has been conserved through positive selection, because it facilitated the generation of phenotypic variation during eukaryotic evolution.

How MAP kinase modules function as robust, yet adaptable, circuits

PubMed Central

Tian, Tianhai; Harding, Angus

2014-01-01

Genetic and biochemical studies have revealed that the diversity of cell types and developmental patterns evident within the animal kingdom is generated by a handful of conserved, core modules. Core biological modules must be robust, able to maintain functionality despite perturbations, and yet sufficiently adaptable for random mutations to generate phenotypic variation during evolution. Understanding how robust, adaptable modules have influenced the evolution of eukaryotes will inform both evolutionary and synthetic biology. One such system is the MAP kinase module, which consists of a 3-tiered kinase circuit configuration that has been evolutionarily conserved from yeast to man. MAP kinase signal transduction pathways are used across eukaryotic phyla to drive biological functions that are crucial for life. Here we ask the fundamental question, why do MAPK modules follow a conserved 3-tiered topology rather than some other number? Using computational simulations, we identify a fundamental 2-tiered circuit topology that can be readily reconfigured by feedback loops and scaffolds to generate diverse signal outputs. When this 2-kinase circuit is connected to proximal input kinases, a 3-tiered modular configuration is created that is both robust and adaptable, providing a biological circuit that can regulate multiple phenotypes and maintain functionality in an uncertain world. We propose that the 3-tiered signal transduction module has been conserved through positive selection, because it facilitated the generation of phenotypic variation during eukaryotic evolution. PMID:25483189

Processing circuit with asymmetry corrector and convolutional encoder for digital data

NASA Technical Reports Server (NTRS)

Pfiffner, Harold J. (Inventor)

1987-01-01

A processing circuit is provided for correcting for input parameter variations, such as data and clock signal symmetry, phase offset and jitter, noise and signal amplitude, in incoming data signals. An asymmetry corrector circuit performs the correcting function and furnishes the corrected data signals to a convolutional encoder circuit. The corrector circuit further forms a regenerated clock signal from clock pulses in the incoming data signals and another clock signal at a multiple of the incoming clock signal. These clock signals are furnished to the encoder circuit so that encoded data may be furnished to a modulator at a high data rate for transmission.

System and method for monitoring and controlling stator winding temperature in a de-energized AC motor

DOEpatents

Lu, Bin [Kenosha, WI; Luebke, Charles John [Sussex, WI; Habetler, Thomas G [Snellville, GA; Zhang, Pinjia [Atlanta, GA; Becker, Scott K [Oak Creek, WI

2011-12-27

A system and method for measuring and controlling stator winding temperature in an AC motor while idling is disclosed. The system includes a circuit having an input connectable to an AC source and an output connectable to an input terminal of a multi-phase AC motor. The circuit further includes a plurality of switching devices to control current flow and terminal voltages in the multi-phase AC motor and a controller connected to the circuit. The controller is configured to activate the plurality of switching devices to create a DC signal in an output of the motor control device corresponding to an input to the multi-phase AC motor, determine or estimate a stator winding resistance of the multi-phase AC motor based on the DC signal, and estimate a stator temperature from the stator winding resistance. Temperature can then be controlled and regulated by DC injection into the stator windings.

Involvement of BDNF signaling transmission from basolateral amygdala to infralimbic prefrontal cortex in conditioned taste aversion extinction.

PubMed

Xin, Jian; Ma, Ling; Zhang, Tian-Yi; Yu, Hui; Wang, Yue; Kong, Liang; Chen, Zhe-Yu

2014-05-21

Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase receptor B (TrkB), play a critical role in memory extinction. However, the detailed role of BDNF in memory extinction on the basis of neural circuit has not been fully understood. Here, we aim to investigate the role of BDNF signaling circuit in mediating conditioned taste aversion (CTA) memory extinction of the rats. We found region-specific changes in BDNF gene expression during CTA extinction. CTA extinction led to increased BDNF gene expression in the basolateral amygdala (BLA) and infralimbic prefrontal cortex (IL) but not in the central amygdaloid nucleus (CeA) and hippocampus (HIP). Moreover, blocking BDNF signaling or exogenous microinjection of BDNF into the BLA or IL could disrupt or enhance CTA extinction, which suggested that BDNF signaling in the BLA and IL is necessary and sufficient for CTA extinction. Interestingly, we found that microinjection of BDNF-neutralizing antibody into the BLA could abolish the extinction training-induced BDNF mRNA level increase in the IL, but not vice versa, demonstrating that BDNF signaling is transmitted from the BLA to IL during extinction. Finally, the accelerated extinction learning by infusion of exogenous BDNF in the BLA could also be blocked by IL infusion of BDNF-neutralizing antibody rather than vice versa, indicating that the IL, but not BLA, is the primary action site of BDNF in CTA extinction. Together, these data suggest that BLA-IL circuit regulates CTA memory extinction by identifying BDNF as a key regulator. Copyright © 2014 the authors 0270-6474/14/347302-12$15.00/0.

Ground Isolation Circuit for Isolating a Transmission Line from Ground Interference

NASA Technical Reports Server (NTRS)

Davidson, Craig A. (Inventor)

1996-01-01

This invention relates generally to a system for isolating ground interference from a transmission line, e.g., a ground isolation circuit for isolating a wideband transmission signal (such as a video signal) from ground by modulating the base signal on a carrier signal to permit the transmission signal to be isolated. In one embodiment, the circuit includes a pair of matched mixer circuits, each of which receives a carrier signal from the same oscillator circuit. The first mixer circuit also receives the baseband signal input, after appropriate conditioning, and modulates the baseband signal onto the carrier signal. In a preferred embodiment the carrier signal has a predetermined frequency which is at least two times the frequency of the baseband signal. The modulated signal (which can comprise an rf signal) is transmitted via an rf transmission line to the second mixer, which demodulates the rf signal to recover the baseband signal. Each port of the mixer connects to an isolation transformer to ensure isolation from ground interference. The circuit is considered to be of commercial value in that it can provide isolation between transmitting and receiving circuits, e.g., ground isolation for television circuits or high frequency transmitters, without the need for video transformers or optical isolators, thereby reducing the complexity, power consumption, and weight of the system.

Regulation of behavioral plasticity by systemic temperature signaling in Caenorhabditis elegans.

PubMed

Sugi, Takuma; Nishida, Yukuo; Mori, Ikue

2011-06-26

Animals cope with environmental changes by altering behavioral strategy. Environmental information is generally received by sensory neurons in the neural circuit that generates behavior. However, although environmental temperature inevitably influences an animal's entire body, the mechanism of systemic temperature perception remains largely unknown. We show here that systemic temperature signaling induces a change in a memory-based behavior in C. elegans. During behavioral conditioning, non-neuronal cells as well as neuronal cells respond to cultivation temperature through a heat-shock transcription factor that drives newly identified gene expression dynamics. This systemic temperature signaling regulates thermosensory neurons non-cell-autonomously through the estrogen signaling pathway, producing thermotactic behavior. We provide a link between systemic environmental recognition and behavioral plasticity in the nervous system.

Antagonistic Serotonergic and Octopaminergic Neural Circuits Mediate Food-Dependent Locomotory Behavior in Caenorhabditis elegans

PubMed Central

McCloskey, Richard J.; Peters, Emily

2017-01-01

Biogenic amines are conserved signaling molecules that link food cues to behavior and metabolism in a wide variety of organisms. In the nematode Caenorhabditis elegans, the biogenic amines serotonin (5-HT) and octopamine regulate a number of food-related behaviors. Using a novel method for long-term quantitative behavioral imaging, we show that 5-HT and octopamine jointly influence locomotor activity and quiescence in feeding and fasting hermaphrodites, and we define the neural circuits through which this modulation occurs. We show that 5-HT produced by the ADF neurons acts via the SER-5 receptor in muscles and neurons to suppress quiescent behavior and promote roaming in fasting worms, whereas 5-HT produced by the NSM neurons acts on the MOD-1 receptor in AIY neurons to promote low-amplitude locomotor behavior characteristic of well fed animals. Octopamine, produced by the RIC neurons, acts via SER-3 and SER-6 receptors in SIA neurons to promote roaming behaviors characteristic of fasting animals. We find that 5-HT signaling is required for animals to assume food-appropriate behavior, whereas octopamine signaling is required for animals to assume fasting-appropriate behavior. The requirement for both neurotransmitters in both the feeding and fasting states enables increased behavioral adaptability. Our results define the molecular and neural pathways through which parallel biogenic amine signaling tunes behavior appropriately to nutrient conditions. SIGNIFICANCE STATEMENT Animals adjust behavior in response to environmental changes, such as fluctuations in food abundance, to maximize survival and reproduction. Biogenic amines, such as like serotonin, are conserved neurotransmitters that regulate behavior and metabolism in relation to energy status. Disruptions of biogenic amine signaling contribute to human neurological diseases of mood, appetite, and movement. In this study, we investigated the roles of the biogenic amines serotonin and octopamine in regulating locomotion behaviors associated with feeding and fasting in the roundworm Caenorhabditis elegans. We identified neural circuits through which these signals work to govern behavior. Understanding the molecular pathways through which biogenic amines function in model organisms may improve our understanding of dysfunctions of appetite and behavior found in mammals, including humans. PMID:28698386

Producing the Ethylene Signal: Regulation and Diversification of Ethylene Biosynthetic Enzymes1

PubMed Central

Booker, Matthew A.; DeLong, Alison

2015-01-01

Strictly controlled production of ethylene gas lies upstream of the signaling activities of this crucial regulator throughout the plant life cycle. Although the biosynthetic pathway is enzymatically simple, the regulatory circuits that modulate signal production are fine tuned to allow integration of responses to environmental and intrinsic cues. Recently identified posttranslational mechanisms that control ethylene production converge on one family of biosynthetic enzymes and overlay several independent reversible phosphorylation events and distinct mediators of ubiquitin-dependent protein degradation. Although the core pathway is conserved throughout seed plants, these posttranslational regulatory mechanisms may represent evolutionarily recent innovations. The evolutionary origins of the pathway and its regulators are not yet clear; outside the seed plants, numerous biochemical and phylogenetic questions remain to be addressed. PMID:26134162

Focal plane infrared readout circuit with automatic background suppression

NASA Technical Reports Server (NTRS)

Pain, Bedabrata (Inventor); Yang, Guang (Inventor); Sun, Chao (Inventor); Shaw, Timothy J. (Inventor); Wrigley, Chris J. (Inventor)

2002-01-01

A circuit for reading out a signal from an infrared detector includes a current-mode background-signal subtracting circuit having a current memory which can be enabled to sample and store a dark level signal from the infrared detector during a calibration phase. The signal stored by the current memory is subtracted from a signal received from the infrared detector during an imaging phase. The circuit also includes a buffered direct injection input circuit and a differential voltage readout section. By performing most of the background signal estimation and subtraction in a current mode, a low gain can be provided by the buffered direct injection input circuit to keep the gain of the background signal relatively small, while a higher gain is provided by the differential voltage readout circuit. An array of such readout circuits can be used in an imager having an array of infrared detectors. The readout circuits can provide a high effective handling capacity.

Top-Down Regulation of Laminar Circuit via Inter-Area Signal for Successful Object Memory Recall in Monkey Temporal Cortex.

PubMed

Takeda, Masaki; Koyano, Kenji W; Hirabayashi, Toshiyuki; Adachi, Yusuke; Miyashita, Yasushi

2015-05-06

Memory retrieval in primates is orchestrated by a brain-wide neuronal circuit. To elucidate the operation of this circuit, it is imperative to comprehend neuronal mechanisms of coordination between area-to-area interaction and information processing within individual areas. By simultaneous recording from area 36 (A36) and area TE (TE) of the temporal cortex while monkeys performed a pair-association memory task, we found two distinct inter-area signal flows during memory retrieval: A36 spiking activity exhibited coherence with low-frequency field activity in either the supragranular or infragranular layer of TE. Of these two flows, only signal flow targeting the infragranular layer of TE was further translaminarly coupled with gamma activity in the supragranular layer of TE. Moreover, this coupling was observed when monkeys succeeded in the retrieval of the sought object but not when they failed. The results suggest that local translaminar processing can be recruited via a layer-specific inter-area network for memory retrieval. Copyright © 2015 Elsevier Inc. All rights reserved.

Design of Tunable Oscillatory Dynamics in a Synthetic NF-κB Signaling Circuit.

PubMed

Zhang, Zhi-Bo; Wang, Qiu-Yue; Ke, Yu-Xi; Liu, Shi-Yu; Ju, Jian-Qi; Lim, Wendell A; Tang, Chao; Wei, Ping

2017-11-22

Although oscillatory circuits are prevalent in transcriptional regulation, it is unclear how a circuit's structure and the specific parameters that describe its components determine the shape of its oscillations. Here, we engineer a minimal, inducible human nuclear factor κB (NF-κB)-based system that is composed of NF-κB (RelA) and degradable inhibitor of NF-κB (IκBα), into the yeast, Saccharomyces cerevisiae. We define an oscillation's waveform quantitatively as a function of signal amplitude, rest time, rise time, and decay time; by systematically tuning RelA concentration, the strength of negative feedback, and the degradation rate of IκBα, we demonstrate that peak shape and frequency of oscillations can be controlled in vivo and predicted mathematically. In addition, we show that nested negative feedback loops can be employed to specifically tune the frequency of oscillations while leaving their peak shape unchanged. In total, this work establishes design principles that enable function-guided design of oscillatory signaling controllers in diverse synthetic biology applications. Copyright © 2017 Elsevier Inc. All rights reserved.

49 CFR 236.205 - Signal control circuits; requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Signal control circuits; requirements. 236.205..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Block Signal Systems Standards § 236.205 Signal control circuits; requirements. The circuits shall be so...

49 CFR 236.205 - Signal control circuits; requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Signal control circuits; requirements. 236.205..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Block Signal Systems Standards § 236.205 Signal control circuits; requirements. The circuits shall be so...

49 CFR 236.205 - Signal control circuits; requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Signal control circuits; requirements. 236.205..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Block Signal Systems Standards § 236.205 Signal control circuits; requirements. The circuits shall be so...

49 CFR 236.205 - Signal control circuits; requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Signal control circuits; requirements. 236.205..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Block Signal Systems Standards § 236.205 Signal control circuits; requirements. The circuits shall be so...

49 CFR 236.205 - Signal control circuits; requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Signal control circuits; requirements. 236.205..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Block Signal Systems Standards § 236.205 Signal control circuits; requirements. The circuits shall be so...

49 CFR 236.744 - Element, roadway.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Element, roadway. 236.744 Section 236.744 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... signal system, such as electric circuit, inductor, or trip arm to which the locomotive apparatus of such...

System and method for regulating resonant inverters

DOEpatents

Stevanovic, Ljubisa Dragoljub [Clifton Park, NY; Zane, Regan Andrew [Superior, CO

2007-08-28

A technique is provided for direct digital phase control of resonant inverters based on sensing of one or more parameters of the resonant inverter. The resonant inverter control system includes a switching circuit for applying power signals to the resonant inverter and a sensor for sensing one or more parameters of the resonant inverter. The one or more parameters are representative of a phase angle. The resonant inverter control system also includes a comparator for comparing the one or more parameters to a reference value and a digital controller for determining timing of the one or more parameters and for regulating operation of the switching circuit based upon the timing of the one or more parameters.

Pairing Increases Activation of V1aR, but not OTR, in Auditory Regions of Zebra Finches: The Importance of Signal Modality in Nonapeptide-Social Behavior Relationships.

PubMed

Tomaszycki, Michelle L; Atchley, Derek

2017-10-01

Social relationships are complex, involving the production and comprehension of signals, individual recognition, and close coordination of behavior between two or more individuals. The nonapeptides oxytocin and vasopressin are widely believed to regulate social relationships. These findings come largely from prairie voles, in which nonapeptide receptors in olfactory neural circuits drive pair bonding. This research is assumed to apply to all species. Previous reviews have offered two competing hypotheses. The work of Sarah Newman has implicated a common neural network across species, the Social Behavior Network. In contrast, others have suggested that there are signal modality-specific networks that regulate social behavior. Our research focuses on evaluating these two competing hypotheses in the zebra finch, a species that relies heavily on vocal/auditory signals for communication, specifically the neural circuits underlying singing in males and song perception in females. We have demonstrated that the quality of vocal interactions is highly important for the formation of long-term monogamous bonds in zebra finches. Qualitative evidence at first suggests that nonapeptide receptor distributions are very different between monogamous rodents (olfactory species) and monogamous birds (vocal/auditory species). However, we have demonstrated that social bonding behaviors are not only correlated with activation of nonapeptide receptors in vocal and auditory circuits, but also involve regions of the common Social Behavior Network. Here, we show increased Vasopressin 1a receptor, but not oxytocin receptor, activation in two auditory regions following formation of a pair bond. To our knowledge, this is the first study to suggest a role of nonapeptides in the auditory circuit in pair bonding. Thus, we highlight converging mechanisms of social relationships and also point to the importance of studying multiple species to understand mechanisms of behavior. © The Author 2017. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Adaptive noise reduction circuit for a sound reproduction system

NASA Technical Reports Server (NTRS)

Engebretson, A. Maynard (Inventor); O'Connell, Michael P. (Inventor)

1995-01-01

A noise reduction circuit for a hearing aid having an adaptive filter for producing a signal which estimates the noise components present in an input signal. The circuit includes a second filter for receiving the noise-estimating signal and modifying it as a function of a user's preference or as a function of an expected noise environment. The circuit also includes a gain control for adjusting the magnitude of the modified noise-estimating signal, thereby allowing for the adjustment of the magnitude of the circuit response. The circuit also includes a signal combiner for combining the input signal with the adjusted noise-estimating signal to produce a noise reduced output signal.

49 CFR 236.201 - Track-circuit control of signals.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Block Signal Systems Standards § 236.201 Track-circuit control of signals. The control circuits for home... 49 Transportation 4 2011-10-01 2011-10-01 false Track-circuit control of signals. 236.201 Section...

49 CFR 236.201 - Track-circuit control of signals.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Block Signal Systems Standards § 236.201 Track-circuit control of signals. The control circuits for home... 49 Transportation 4 2010-10-01 2010-10-01 false Track-circuit control of signals. 236.201 Section...

Ccl5 establishes an autocrine high-grade glioma growth regulatory circuit critical for mesenchymal glioblastoma survival

PubMed Central

Pan, Yuan; Smithson, Laura J.; Ma, Yu; Hambardzumyan, Dolores; Gutmann, David H.

2017-01-01

Glioblastoma (GBM) is the most common malignant brain tumor in adults, with a median survival of 15 months. These poor clinical outcomes have prompted the development of drugs that block neoplastic cancer cell growth; however, non-neoplastic cell-derived signals (chemokines and cytokines) in the tumor microenvironment may also represent viable treatment targets. One such chemokine, Ccl5, produced by low-grade tumor-associated microglia, is responsible for maintaining neurofibromatosis type 1 (NF1) mouse optic glioma growth in vivo. Since malignant gliomas may achieve partial independence from growth regulatory factors produced by non-neoplastic cells in the tumor microenvironment by producing the same cytokines secreted by the stromal cells in their low-grade counterparts, we tested the hypothesis that CCL5/CCL5-receptor signaling in glioblastoma creates an autocrine circuit important for high-grade glioma growth. Herein, we demonstrate that increased CCL5 expression was restricted to both human and mouse mesenchymal GBM (M-GBM), a molecular subtype characterized by NF1 loss. We further show that the NF1 protein, neurofibromin, negatively regulates Ccl5 expression through suppression of AKT/mTOR signaling. Consistent with its role as a glioblastoma growth regulator, Ccl5 knockdown in M-GBM cells reduces M-GBM cell survival in vitro, and increases mouse glioblastoma survival in vivo. Finally, we demonstrate that Ccl5 operates through an unconventional CCL5 receptor, CD44, to inhibit M-GBM apoptosis. Collectively, these findings reveal an NF1-dependent CCL5-mediated pathway that regulates M-GBM cell survival, and support the concept that paracrine factors important for low-grade glioma growth can be usurped by high-grade tumors to create autocrine regulatory circuits that maintain malignant glioma survival. PMID:28380429

Synthetic in vitro transcriptional oscillators

PubMed Central

Kim, Jongmin; Winfree, Erik

2011-01-01

The construction of synthetic biochemical circuits from simple components illuminates how complex behaviors can arise in chemistry and builds a foundation for future biological technologies. A simplified analog of genetic regulatory networks, in vitro transcriptional circuits, provides a modular platform for the systematic construction of arbitrary circuits and requires only two essential enzymes, bacteriophage T7 RNA polymerase and Escherichia coli ribonuclease H, to produce and degrade RNA signals. In this study, we design and experimentally demonstrate three transcriptional oscillators in vitro. First, a negative feedback oscillator comprising two switches, regulated by excitatory and inhibitory RNA signals, showed up to five complete cycles. To demonstrate modularity and to explore the design space further, a positive-feedback loop was added that modulates and extends the oscillatory regime. Finally, a three-switch ring oscillator was constructed and analyzed. Mathematical modeling guided the design process, identified experimental conditions likely to yield oscillations, and explained the system's robust response to interference by short degradation products. Synthetic transcriptional oscillators could prove valuable for systematic exploration of biochemical circuit design principles and for controlling nanoscale devices and orchestrating processes within artificial cells. PMID:21283141

Technique for extending the range of a signal measuring circuit

DOEpatents

Chaprnka, Anthony G.; Sun, Shan C.; Vercellotti, Leonard C.

1978-01-01

An input signal supplied to a signal measuring circuit is either amplified or attenuated as necessary to establish the magnitude of the input signal within the defined dynamic range of the measuring circuit and the output signal developed by the measuring circuit is subsequently readjusted through amplification or attenuation to develop an output signal which corresponds to the magnitude of the initial input signal.

CB1 Cannabinoid Receptor Expression in the Striatum: Association with Corticostriatal Circuits and Developmental Regulation

PubMed Central

Van Waes, Vincent; Beverley, Joel A.; Siman, Homayoun; Tseng, Kuei Y.; Steiner, Heinz

2012-01-01

Corticostriatal circuits mediate various aspects of goal-directed behavior and are critically important for basal ganglia-related disorders. Activity in these circuits is regulated by the endocannabinoid system via stimulation of CB1 cannabinoid receptors. CB1 receptors are highly expressed in projection neurons and select interneurons of the striatum, but expression levels vary considerably between different striatal regions (functional domains). We investigated CB1 receptor expression within specific corticostriatal circuits by mapping CB1 mRNA levels in striatal sectors defined by their cortical inputs in rats. We also assessed changes in CB1 expression in the striatum during development. Our results show that CB1 expression is highest in juveniles (P25) and then progressively decreases toward adolescent (P40) and adult (P70) levels. At every age, CB1 receptors are predominantly expressed in sensorimotor striatal sectors, with considerably lower expression in associative and limbic sectors. Moreover, for most corticostriatal circuits there is an inverse relationship between cortical and striatal expression levels. Thus, striatal sectors with high CB1 expression (sensorimotor sectors) tend to receive inputs from cortical areas with low expression, while striatal sectors with low expression (associative/limbic sectors) receive inputs from cortical regions with higher expression (medial prefrontal cortex). In so far as CB1 mRNA levels reflect receptor function, our findings suggest differential CB1 signaling between different developmental stages and between sensorimotor and associative/limbic circuits. The regional distribution of CB1 receptor expression in the striatum further suggests that, in sensorimotor sectors, CB1 receptors mostly regulate GABA inputs from local axon collaterals of projection neurons, whereas in associative/limbic sectors, CB1 regulation of GABA inputs from interneurons and glutamate inputs may be more important. PMID:22416230

Orphanin FQ-ORL-1 regulation of reproduction and reproductive behavior in the female.

PubMed

Sinchak, Kevin; Dalhousay, Lauren; Sanathara, Nayna

2015-01-01

Orphanin FQ (OFQ/N) and its receptor, opioid receptor-like receptor-1 (ORL-1), are expressed throughout steroid-responsive limbic and hypothalamic circuits that regulate female ovarian hormone feedback and reproductive behavior circuits. The arcuate nucleus of the hypothalamus (ARH) is a brain region that expresses OFQ/N and ORL-1 important for both sexual behavior and modulating estradiol feedback loops. Within the ARH, the activation of the OFQ/N-ORL-1 system facilitates sexual receptivity (lordosis) through the inhibition of β-endorphin neuronal activity. Estradiol initially activates ARH β-endorphin neurons to inhibit lordosis. Simultaneously, estradiol upregulates coexpression of OFQ/N and progesterone receptors and ORL-1 in ARH β-endorphin neurons. Ovarian hormones regulate pre- and postsynaptic coupling of ORL-1 to its G protein-coupled signaling pathways. When the steroid-primed rat is nonreceptive, estradiol acts pre- and postsynaptically to decrease the ability of the OFQ/N-ORL-1 system to inhibit ARH β-endorphin neurotransmission. Conversely, when sexually receptive, ORL-1 signaling is restored to inhibit β-endorphin neurotransmission. Although steroid signaling that facilitates lordosis converges to deactivate ARH β-endorphin neurons, estradiol-only facilitation of lordosis requires the activation of ORL-1, but estradiol+progesterone does not, indicating that multiple circuits mediate ovarian hormone signaling to deactivate ARH β-endorphin neurons. Research on the role of OFQ/N-ORL-1 in ovarian hormone feedback loops is just beginning. In the rat, OFQ/N may act to terminate gonadotropin-releasing hormone and luteinizing hormone release under positive and negative feedbacks. In the ewe, it appears to directly inhibit gonadotropin-releasing hormone release to mediate progesterone-negative feedback. As a whole, the localization and actions of OFQ/N-ORL-1 system indicate that it may mediate the actions of estradiol and progesterone to synchronize reproductive behavior and ovarian hormone feedback loops. © 2015 Elsevier Inc. All rights reserved.

Thermocouple-Signal-Conditioning Circuit

NASA Technical Reports Server (NTRS)

Simon, Richard A.

1991-01-01

Thermocouple-signal-conditioning circuit acting in conjunction with thermocouple, exhibits electrical behavior of voltage in series with resistance. Combination part of input bridge circuit of controller. Circuit configured for either of two specific applications by selection of alternative resistances and supply voltages. Includes alarm circuit detecting open circuit in thermocouple and provides off-scale output to signal malfunctions.

An IκB Kinase-regulated feed-forward circuit prolongs inflammation

PubMed Central

Perez, Jessica M.; Chirieleison, Steven M.; Abbott, Derek W.

2015-01-01

Summary Loss of NF-κB signaling causes immunodeficiency while inhibition of NF-κB can be efficacious in treating chronic inflammatory disease. Inflammatory NF-κB signaling must therefore be tightly regulated, and while many mechanisms to downregulate NF-κB have been elucidated, there have only been limited studies demonstrating positive feed-forward regulation of NF-κB signaling. In this work, we use a bioinformatic and proteomic approach to discover that the IKK family of proteins can phosphorylate the E3 ubiquitin ligase, ITCH, a critical downregulator of TNF-mediated NF-κB activation. Phosphorylation of ITCH by IKKs leads to impaired ITCH E3 ubiquitin ligase activity and prolongs NF-κB signaling and pro-inflammatory cytokine release. Since genetic loss of ITCH mirrors IKK-induced ITCH phosphorylation, we further show that the ITCH−/− mouse’s spontaneous lung inflammation and subsequent death can be delayed when TNF signaling is genetically deleted. This work thus identifies a new positive feed-forward regulation of NF-kB activation that drives inflammatory disease. PMID:26190110

Corticotropin-Releasing Factor Critical for Zebrafish Camouflage Behavior Is Regulated by Light and Sensitive to Ethanol

PubMed Central

Wagle, Mahendra; Mathur, Priya; Guo, Su

2011-01-01

The zebrafish camouflage response is an innate “hard-wired” behavior that offers an excellent opportunity to explore neural circuit assembly and function. Moreover, the camouflage response is sensitive to ethanol, making it a tractable system for understanding how ethanol influences neural circuit development and function. Here we report the identification of corticotropin releasing factor (CRF) as a critical component of the camouflage response pathway. We further show that ethanol, having no direct effect on the visual sensory system or the melanocytes, acts downstream of retinal ganglion cells and requires the CRF-proopiomelanocortin (POMC) pathway to exert its effect on camouflage. Treatment with ethanol, as well as alteration of light exposure that changes sensory input into the camouflage circuit, robustly modifies CRF expression in subsets of neurons. Activity of both Adenylyl Cyclase 5 and Extracellular signal Regulated Kinase (ERK) is required for such ethanol- or light- induced plasticity of crf expression. These results reveal an essential role of a peptidergic pathway in camouflage that is regulated by light and influenced by ethanol at concentrations relevant to abuse and anxiolysis, in a cAMP- and ERK- dependent manner. We conclude that this ethanol-modulated camouflage response represents a novel and relevant system for molecular genetic dissection of a neural circuit that is regulated by light and sensitive to ethanol. PMID:21209207

Corticotropin-releasing factor critical for zebrafish camouflage behavior is regulated by light and sensitive to ethanol.

PubMed

Wagle, Mahendra; Mathur, Priya; Guo, Su

2011-01-05

The zebrafish camouflage response is an innate "hard-wired" behavior that offers an excellent opportunity to explore neural circuit assembly and function. Moreover, the camouflage response is sensitive to ethanol, making it a tractable system for understanding how ethanol influences neural circuit development and function. Here we report the identification of corticotropin-releasing factor (CRF) as a critical component of the camouflage response pathway. We further show that ethanol, having no direct effect on the visual sensory system or the melanocytes, acts downstream of retinal ganglion cells and requires the CRF-proopiomelanocortin pathway to exert its effect on camouflage. Treatment with ethanol, as well as alteration of light exposure that changes sensory input into the camouflage circuit, robustly modifies CRF expression in subsets of neurons. Activity of both adenylyl cyclase 5 and extracellular signal-regulated kinase (ERK) is required for such ethanol-induced or light-induced plasticity of crf expression. These results reveal an essential role of a peptidergic pathway in camouflage that is regulated by light and influenced by ethanol at concentrations relevant to abuse and anxiolysis, in a cAMP-dependent and ERK-dependent manner. We conclude that this ethanol-modulated camouflage response represents a novel and relevant system for molecular genetic dissection of a neural circuit that is regulated by light and sensitive to ethanol.

Phosphate Sink Containing Two-Component Signaling Systems as Tunable Threshold Devices

PubMed Central

Amin, Munia; Kothamachu, Varun B.; Feliu, Elisenda; Scharf, Birgit E.; Porter, Steven L.; Soyer, Orkun S.

2014-01-01

Synthetic biology aims to design de novo biological systems and reengineer existing ones. These efforts have mostly focused on transcriptional circuits, with reengineering of signaling circuits hampered by limited understanding of their systems dynamics and experimental challenges. Bacterial two-component signaling systems offer a rich diversity of sensory systems that are built around a core phosphotransfer reaction between histidine kinases and their output response regulator proteins, and thus are a good target for reengineering through synthetic biology. Here, we explore the signal-response relationship arising from a specific motif found in two-component signaling. In this motif, a single histidine kinase (HK) phosphotransfers reversibly to two separate output response regulator (RR) proteins. We show that, under the experimentally observed parameters from bacteria and yeast, this motif not only allows rapid signal termination, whereby one of the RRs acts as a phosphate sink towards the other RR (i.e. the output RR), but also implements a sigmoidal signal-response relationship. We identify two mathematical conditions on system parameters that are necessary for sigmoidal signal-response relationships and define key parameters that control threshold levels and sensitivity of the signal-response curve. We confirm these findings experimentally, by in vitro reconstitution of the one HK-two RR motif found in the Sinorhizobium meliloti chemotaxis pathway and measuring the resulting signal-response curve. We find that the level of sigmoidality in this system can be experimentally controlled by the presence of the sink RR, and also through an auxiliary protein that is shown to bind to the HK (yielding Hill coefficients of above 7). These findings show that the one HK-two RR motif allows bacteria and yeast to implement tunable switch-like signal processing and provides an ideal basis for developing threshold devices for synthetic biology applications. PMID:25357192

Multi-channel detector readout method and integrated circuit

DOEpatents

Moses, William W.; Beuville, Eric; Pedrali-Noy, Marzio

2006-12-12

An integrated circuit which provides multi-channel detector readout from a detector array. The circuit receives multiple signals from the elements of a detector array and compares the sampled amplitudes of these signals against a noise-floor threshold and against one another. A digital signal is generated which corresponds to the location of the highest of these signal amplitudes which exceeds the noise floor threshold. The digital signal is received by a multiplexing circuit which outputs an analog signal corresponding the highest of the input signal amplitudes. In addition a digital control section provides for programmatic control of the multiplexer circuit, amplifier gain, amplifier reset, masking selection, and test circuit functionality on each input thereof.

Multi-channel detector readout method and integrated circuit

DOEpatents

Moses, William W.; Beuville, Eric; Pedrali-Noy, Marzio

2004-05-18

An integrated circuit which provides multi-channel detector readout from a detector array. The circuit receives multiple signals from the elements of a detector array and compares the sampled amplitudes of these signals against a noise-floor threshold and against one another. A digital signal is generated which corresponds to the location of the highest of these signal amplitudes which exceeds the noise floor threshold. The digital signal is received by a multiplexing circuit which outputs an analog signal corresponding the highest of the input signal amplitudes. In addition a digital control section provides for programmatic control of the multiplexer circuit, amplifier gain, amplifier reset, masking selection, and test circuit functionality on each input thereof.

Climacteric ripening of apple fruit is regulated by transcriptional circuits stimulated by cross-talks between ethylene and auxin.

PubMed

Busatto, Nicola; Tadiello, Alice; Trainotti, Livio; Costa, Fabrizio

2017-01-02

Apple is a fleshy fruit distinguished by a climacteric type of ripening, since most of the relevant physiological changes are triggered and governed by the action of ethylene. After its production, this hormone is perceived by a series of receptors to regulate, through a signaling cascade, downstream ethylene related genes. The possibility to control the effect of ethylene opened new horizons to the improvement of the postharvest fruit quality. To this end, 1-methylcyclopropene (1-MCP), an ethylene antagonist, is routinely used to modulate the ripening progression increasing storage life. In a recent work published in The Plant Journal, the whole transcriptome variation throughout fruit development and ripening, with the adjunct comparison between normal and impaired postharvest ripening, has been illustrated. In particular, besides the expected downregulation of ethylene-regulated genes, we shed light on a regulatory circuit leading to de-repressing the expression of a specific set of genes following 1-MCP treatment, such as AUX/IAA, NAC and MADS. These findings suggested the existence of a possible ethylene/auxin cross-talk in apple, regulated by a transcriptional circuit stimulated by the interference at the ethylene receptor level.

The research of PSD location method in micro laser welding fields

NASA Astrophysics Data System (ADS)

Zhang, Qiue; Zhang, Rong; Dong, Hua

2010-11-01

In the field of micro laser welding, besides the special requirement in the parameter of lasers, the locating in welding points accurately is very important. The article adopt position sensitive detector (PSD) as hard core, combine optic system, electric circuits and PC and software processing, confirm the location of welding points. The signal detection circuits adopt the special integrate circuit H-2476 to process weak signal. It is an integrated circuit for high-speed, high-sensitivity optical range finding, which has stronger noiseproof feature, combine digital filter arithmetic, carry out repair the any non-ideal factors, increasing the measure precision. The amplifier adopt programmable amplifier LTC6915. The system adapt two dimension stepping motor drive the workbench, computer and corresponding software processing, make sure the location of spot weld. According to different workpieces to design the clamps. The system on-line detect PSD 's output signal in the moving processing. At the workbench moves in the X direction, the filaments offset is detected dynamic. Analyze the X axes moving sampling signal direction could be estimate the Y axes moving direction, and regulate the Y axes moving values. The workbench driver adopt A3979, it is a stepping motor driver with insert transducer and operate easily. It adapts the requirement of location in micro laser welding fields, real-time control to adjust by computer. It can be content up 20 μm's laser micro welding requirement on the whole. Using laser powder cladding technology achieve inter-penetration welding of high quality and reliability.

Cellular complexity in subcortical white matter: a distributed control circuit?

PubMed

Colombo, Jorge A

2018-03-01

The subcortical white matter (SWM) has been traditionally considered as a site for passive-neutral-information transfer through cerebral cortex association and projection fibers. Yet, the presence of subcortical neuronal and glial "interstitial" cells expressing immunolabelled neurotransmitters/neuromodulators and synaptic vesicular proteins, and recent immunohistochemical and electrophysiological observations on the rat visual cortex as well as interactive regulation of myelinating processes support the possibility that SWM nests subcortical, regionally variable, distributed neuronal-glial circuits, that could influence information transfer. Their hypothetical involvement in regulating the timing and signal transfer probability at the SWM axonal components ought to be considered and experimentally analysed. Thus, the "interstitial" neuronal cells-associated with local glial cells-traditionally considered to be vestigial and functionally inert under normal conditions, they may well turn to be critical in regulating information transfer at the SWM.

High on food: the interaction between the neural circuits for feeding and for reward.

PubMed

Liu, Jing-Jing; Mukherjee, Diptendu; Haritan, Doron; Ignatowska-Jankowska, Bogna; Liu, Ji; Citri, Ami; Pang, Zhiping P

2015-04-01

Hunger, mostly initiated by a deficiency in energy, induces food seeking and intake. However, the drive toward food is not only regulated by physiological needs, but is motivated by the pleasure derived from ingestion of food, in particular palatable foods. Therefore, feeding is viewed as an adaptive motivated behavior that involves integrated communication between homeostatic feeding circuits and reward circuits. The initiation and termination of a feeding episode are instructed by a variety of neuronal signals, and maladaptive plasticity in almost any component of the network may lead to the development of pathological eating disorders. In this review we will summarize the latest understanding of how the feeding circuits and reward circuits in the brain interact. We will emphasize communication between the hypothalamus and the mesolimbic dopamine system and highlight complexities, discrepancies, open questions and future directions for the field.

Principles of Genetic Circuit Design

PubMed Central

Brophy, Jennifer A.N.; Voigt, Christopher A.

2014-01-01

Cells are able to navigate environments, communicate, and build complex patterns by initiating gene expression in response to specific signals. Engineers need to harness this capability to program cells to perform tasks or build chemicals and materials that match the complexity seen in nature. This review describes new tools that aid the construction of genetic circuits. We show how circuit dynamics can be influenced by the choice of regulators and changed with expression “tuning knobs.” We collate the failure modes encountered when assembling circuits, quantify their impact on performance, and review mitigation efforts. Finally, we discuss the constraints that arise from operating within a living cell. Collectively, better tools, well-characterized parts, and a comprehensive understanding of how to compose circuits are leading to a breakthrough in the ability to program living cells for advanced applications, from living therapeutics to the atomic manufacturing of functional materials. PMID:24781324

Superconductor Digital Electronics: -- Current Status, Future Prospects

NASA Astrophysics Data System (ADS)

Mukhanov, Oleg

2011-03-01

Two major applications of superconductor electronics: communications and supercomputing will be presented. These areas hold a significant promise of a large impact on electronics state-of-the-art for the defense and commercial markets stemming from the fundamental advantages of superconductivity: simultaneous high speed and low power, lossless interconnect, natural quantization, and high sensitivity. The availability of relatively small cryocoolers lowered the foremost market barrier for cryogenically-cooled superconductor electronic systems. These fundamental advantages enabled a novel Digital-RF architecture - a disruptive technological approach changing wireless communications, radar, and surveillance system architectures dramatically. Practical results were achieved for Digital-RF systems in which wide-band, multi-band radio frequency signals are directly digitized and digital domain is expanded throughout the entire system. Digital-RF systems combine digital and mixed signal integrated circuits based on Rapid Single Flux Quantum (RSFQ) technology, superconductor analog filter circuits, and semiconductor post-processing circuits. The demonstrated cryocooled Digital-RF systems are the world's first and fastest directly digitizing receivers operating with live satellite signals, enabling multi-net data links, and performing signal acquisition from HF to L-band with 30 GHz clock frequencies. In supercomputing, superconductivity leads to the highest energy efficiencies per operation. Superconductor technology based on manipulation and ballistic transfer of magnetic flux quanta provides a superior low-power alternative to CMOS and other charge-transfer based device technologies. The fundamental energy consumption in SFQ circuits defined by flux quanta energy 2 x 10-19 J. Recently, a novel energy-efficient zero-static-power SFQ technology, eSFQ/ERSFQ was invented, which retains all advantages of standard RSFQ circuits: high-speed, dc power, internal memory. The voltage bias regulation, determined by SFQ clock, enables the zero-power at zero-activity regimes, indispensable for sensor and quantum bit readout.

Advanced capability RFID system

DOEpatents

Gilbert, Ronald W.; Steele, Kerry D.; Anderson, Gordon A.

2007-09-25

A radio-frequency transponder device having an antenna circuit configured to receive radio-frequency signals and to return modulated radio-frequency signals via continuous wave backscatter, a modulation circuit coupled to the antenna circuit for generating the modulated radio-frequency signals, and a microprocessor coupled to the antenna circuit and the modulation circuit and configured to receive and extract operating power from the received radio-frequency signals and to monitor inputs on at least one input pin and to generate responsive signals to the modulation circuit for modulating the radio-frequency signals. The microprocessor can be configured to generate output signals on output pins to associated devices for controlling the operation thereof. Electrical energy can be extracted and stored in an optional electrical power storage device.

Interrogating the topological robustness of gene regulatory circuits by randomization

PubMed Central

Levine, Herbert; Onuchic, Jose N.

2017-01-01

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. PMID:28362798

Gq/5-HT2c receptor signals activate a local GABAergic inhibitory feedback circuit to modulate serotonergic firing and anxiety in mice.

PubMed

Spoida, Katharina; Masseck, Olivia A; Deneris, Evan S; Herlitze, Stefan

2014-04-29

Serotonin 2c receptors (5-HT2c-Rs) are drug targets for certain mental disorders, including schizophrenia, depression, and anxiety. 5-HT2c-Rs are expressed throughout the brain, making it difficult to link behavioral changes to circuit specific receptor expression. Various 5-HT-Rs, including 5-HT2c-Rs, are found in the dorsal raphe nucleus (DRN); however, the function of 5-HT2c-Rs and their influence on the serotonergic signals mediating mood disorders remain unclear. To investigate the role of 5-HT2c-Rs in the DRN in mice, we developed a melanopsin-based optogenetic probe for activation of Gq signals in cellular domains, where 5-HT2c-Rs are localized. Our results demonstrate that precise temporal control of Gq signals in 5-HT2c-R domains in GABAergic neurons upstream of 5-HT neurons provides negative feedback regulation of serotonergic firing to modulate anxiety-like behavior in mice.

Gq/5-HT2c receptor signals activate a local GABAergic inhibitory feedback circuit to modulate serotonergic firing and anxiety in mice

PubMed Central

Spoida, Katharina; Masseck, Olivia A.; Deneris, Evan S.; Herlitze, Stefan

2014-01-01

Serotonin 2c receptors (5-HT2c-Rs) are drug targets for certain mental disorders, including schizophrenia, depression, and anxiety. 5-HT2c-Rs are expressed throughout the brain, making it difficult to link behavioral changes to circuit specific receptor expression. Various 5-HT-Rs, including 5-HT2c-Rs, are found in the dorsal raphe nucleus (DRN); however, the function of 5-HT2c-Rs and their influence on the serotonergic signals mediating mood disorders remain unclear. To investigate the role of 5-HT2c-Rs in the DRN in mice, we developed a melanopsin-based optogenetic probe for activation of Gq signals in cellular domains, where 5-HT2c-Rs are localized. Our results demonstrate that precise temporal control of Gq signals in 5-HT2c-R domains in GABAergic neurons upstream of 5-HT neurons provides negative feedback regulation of serotonergic firing to modulate anxiety-like behavior in mice. PMID:24733892

[Design of High Frequency Signal Detecting Circuit of Human Body Impedance Used for Ultrashort Wave Diathermy Apparatus].

PubMed

Fan, Xu; Wang, Yunguang; Cheng, Haiping; Chong, Xiaochen

2016-02-01

The present circuit was designed to apply to human tissue impedance tuning and matching device in ultra-short wave treatment equipment. In order to judge if the optimum status of circuit parameter between energy emitter circuit and accepter circuit is in well syntony, we designed a high frequency envelope detect circuit to coordinate with automatic adjust device of accepter circuit, which would achieve the function of human tissue impedance matching and tuning. Using the sampling coil to receive the signal of amplitude-modulated wave, we compared the voltage signal of envelope detect circuit with electric current of energy emitter circuit. The result of experimental study was that the signal, which was transformed by the envelope detect circuit, was stable and could be recognized by low speed Analog to Digital Converter (ADC) and was proportional to the electric current signal of energy emitter circuit. It could be concluded that the voltage, transformed by envelope detect circuit can mirror the real circuit state of syntony and realize the function of human tissue impedance collecting.

Logarithmic current measurement circuit with improved accuracy and temperature stability and associated method

DOEpatents

Ericson, M. Nance; Rochelle, James M.

1994-01-01

A logarithmic current measurement circuit for operating upon an input electric signal utilizes a quad, dielectrically isolated, well-matched, monolithic bipolar transistor array. One group of circuit components within the circuit cooperate with two transistors of the array to convert the input signal logarithmically to provide a first output signal which is temperature-dependant, and another group of circuit components cooperate with the other two transistors of the array to provide a second output signal which is temperature-dependant. A divider ratios the first and second output signals to provide a resultant output signal which is independent of temperature. The method of the invention includes the operating steps performed by the measurement circuit.

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

Volkow N. D.; Wang G.; Volkow, N.D.

The ability to resist the urge to eat requires the proper functioning of neuronal circuits involved in top-down control to oppose the conditioned responses that predict reward from eating the food and the desire to eat the food. Imaging studies show that obese subjects might have impairments in dopaminergic pathways that regulate neuronal systems associated with reward sensitivity, conditioning and control. It is known that the neuropeptides that regulate energy balance (homeostatic processes) through the hypothalamus also modulate the activity of dopamine cells and their projections into regions involved in the rewarding processes underlying food intake. It is postulated thatmore » this could also be a mechanism by which overeating and the resultant resistance to homoeostatic signals impairs the function of circuits involved in reward sensitivity, conditioning and cognitive control.« less

Method and apparatus for linear low-frequency feedback in monolithic low-noise charge amplifiers

DOEpatents

DeGeronimo, Gianluigi

2006-02-14

A charge amplifier includes an amplifier, feedback circuit, and cancellation circuit. The feedback circuit includes a capacitor, inverter, and current mirror. The capacitor is coupled across the signal amplifier, the inverter is coupled to the output of the signal amplifier, and the current mirror is coupled to the input of the signal amplifier. The cancellation circuit is coupled to the output of the signal amplifier. A method of charge amplification includes providing a signal amplifier; coupling a first capacitor across the signal amplifier; coupling an inverter to the output of the signal amplifier; coupling a current mirror to the input of the signal amplifier; and coupling a cancellation circuit to the output of the signal amplifier. A front-end system for use with radiation sensors includes a charge amplifier and a current amplifier, shaping amplifier, baseline stabilizer, discriminator, peak detector, timing detector, and logic circuit coupled to the charge amplifier.

Sensitive detection of proteasomal activation using the Deg-On mammalian synthetic gene circuit.

PubMed

Zhao, Wenting; Bonem, Matthew; McWhite, Claire; Silberg, Jonathan J; Segatori, Laura

2014-04-08

The ubiquitin proteasome system (UPS) has emerged as a drug target for diverse diseases characterized by altered proteostasis, but pharmacological agents that enhance UPS activity have been challenging to establish. Here we report the Deg-On system, a genetic inverter that translates proteasomal degradation of the transcriptional regulator TetR into a fluorescent signal, thereby linking UPS activity to an easily detectable output, which can be tuned using tetracycline. We demonstrate that this circuit responds to modulation of UPS activity in cell culture arising from the inhibitor MG-132 and activator PA28γ. Guided by predictive modelling, we enhanced the circuit's signal sensitivity and dynamic range by introducing a feedback loop that enables self-amplification of TetR. By linking UPS activity to a simple and tunable fluorescence output, these genetic inverters will enable a variety of applications, including screening for UPS activating molecules and selecting for mammalian cells with different levels of proteasome activity.

A portable expression resource for engineering cross-species genetic circuits and pathways

PubMed Central

Kushwaha, Manish; Salis, Howard M.

2015-01-01

Genetic circuits and metabolic pathways can be reengineered to allow organisms to process signals and manufacture useful chemicals. However, their functions currently rely on organism-specific regulatory parts, fragmenting synthetic biology and metabolic engineering into host-specific domains. To unify efforts, here we have engineered a cross-species expression resource that enables circuits and pathways to reuse the same genetic parts, while functioning similarly across diverse organisms. Our engineered system combines mixed feedback control loops and cross-species translation signals to autonomously self-regulate expression of an orthogonal polymerase without host-specific promoters, achieving nontoxic and tuneable gene expression in diverse Gram-positive and Gram-negative bacteria. Combining 50 characterized system variants with mechanistic modelling, we show how the cross-species expression resource's dynamics, capacity and toxicity are controlled by the control loops' architecture and feedback strengths. We also demonstrate one application of the resource by reusing the same genetic parts to express a biosynthesis pathway in both model and non-model hosts. PMID:26184393

Inhibitory Control in the Cortico-Basal Ganglia-Thalamocortical Loop: Complex Regulation and Interplay with Memory and Decision Processes.

PubMed

Wei, Wei; Wang, Xiao-Jing

2016-12-07

We developed a circuit model of spiking neurons that includes multiple pathways in the basal ganglia (BG) and is endowed with feedback mechanisms at three levels: cortical microcircuit, corticothalamic loop, and cortico-BG-thalamocortical system. We focused on executive control in a stop signal task, which is known to depend on BG across species. The model reproduces a range of experimental observations and shows that the newly discovered feedback projection from external globus pallidus to striatum is crucial for inhibitory control. Moreover, stopping process is enhanced by the cortico-subcortical reverberatory dynamics underlying persistent activity, establishing interdependence between working memory and inhibitory control. Surprisingly, the stop signal reaction time (SSRT) can be adjusted by weights of certain connections but is insensitive to other connections in this complex circuit, suggesting novel circuit-based intervention for inhibitory control deficits associated with mental illness. Our model provides a unified framework for inhibitory control, decision making, and working memory. Copyright © 2016 Elsevier Inc. All rights reserved.

TOFPET 2: A high-performance circuit for PET time-of-flight

NASA Astrophysics Data System (ADS)

Di Francesco, Agostino; Bugalho, Ricardo; Oliveira, Luis; Rivetti, Angelo; Rolo, Manuel; Silva, Jose C.; Varela, Joao

2016-07-01

We present a readout and digitization ASIC featuring low-noise and low-power for time-of flight (TOF) applications using SiPMs. The circuit is designed in standard CMOS 110 nm technology, has 64 independent channels and is optimized for time-of-flight measurement in Positron Emission Tomography (TOF-PET). The input amplifier is a low impedance current conveyor based on a regulated common-gate topology. Each channel has quad-buffered analogue interpolation TDCs (time binning 20 ps) and charge integration ADCs with linear response at full scale (1500 pC). The signal amplitude can also be derived from the measurement of time-over-threshold (ToT). Simulation results show that for a single photo-electron signal with charge 200 (550) fC generated by a SiPM with (320 pF) capacitance the circuit has 24 (30) dB SNR, 75 (39) ps r.m.s. resolution, and 4 (8) mW power consumption. The event rate is 600 kHz per channel, with up to 2 MHz dark counts rejection.

Hormonal gain control of a medial preoptic area social reward circuit

PubMed Central

McHenry, Jenna A.; Otis, James M.; Rossi, Mark A.; Robinson, J. Elliott; Kosyk, Oksana; Miller, Noah W.; McElligott, Zoe A.; Budygin, Evgeny A.; Rubinow, David R.; Stuber, Garret D.

2017-01-01

Neural networks that control reproduction must integrate social and hormonal signals, tune motivation, and invigorate social interactions. However, the neurocircuit mechanisms for these processes remain unresolved. The medial preoptic area (mPOA), an essential node for social behaviors and is comprised of molecularly-diverse neurons with widespread projections. Here, we identify a steroid-responsive subset of neurotensin (Nts) expressing mPOA neurons that interface with the ventral tegmental area (VTA) to form a socially-engaged reward circuit. Using in vivo 2-photon imaging in female mice, we show that mPOANts neurons preferentially encode attractive male cues compared to non-social appetitive stimuli. Ovarian hormone signals regulate both the physiological and cue encoding properties of these cells. Furthermore, optogenetic stimulation of mPOANts-VTA circuitry promotes rewarding phenotypes, social approach, and striatal dopamine release. Collectively, these data demonstrate that steroid-sensitive mPOA neurons encode ethologically-relevant stimuli and co-opt midbrain reward circuits to promote prosocial behavior critical for species survival. PMID:28135243

Dual amplitude pulse generator for radiation detectors

DOEpatents

Hoggan, Jerry M.; Kynaston, Ronnie L.; Johnson, Larry O.

2001-01-01

A pulsing circuit for producing an output signal having a high amplitude pulse and a low amplitude pulse may comprise a current source for providing a high current signal and a low current signal. A gate circuit connected to the current source includes a trigger signal input that is responsive to a first trigger signal and a second trigger signal. The first trigger signal causes the gate circuit to connect the high current signal to a pulse output terminal whereas the second trigger signal causes the gate circuit to connect the low current signal to the pulse output terminal.

Opiate-associated contextual memory formation and retrieval are differentially modulated by dopamine D1 and D2 signaling in hippocampal-prefrontal connectivity.

PubMed

Wang, Yunpeng; Zhang, Hongying; Cui, Jingjing; Zhang, Jing; Yin, Fangyuan; Guo, Hao; Lai, Jianghua; Xing, Bo

2018-04-17

Contextual memory driven by abused drugs such as opiates has a central role in maintenance and relapse of drug-taking behaviors. Although dopamine (DA) signaling favors memory storage and retrieval via regulation of hippocampal-prefrontal connectivity, its role in modulating opiate-associated contextual memory is largely unknown. Here, we report roles of DA signaling within the hippocampal-prefrontal circuit for opiate-related memories. Combining-conditioned place preference (CPP) with molecular analyses, we investigated the DA D1 receptor (D1R) and extracellular signal-regulated kinase (ERK)-cAMP-response element binding protein (CREB) signaling, as well as DA D2 receptor (D2R) and protein kinase B (PKB or Akt)/glycogen synthase kinase 3 (GSK3) signaling in the ventral hippocampus (vHip) and medial prefrontal cortex (mPFC) during the formation of opiate-related associative memories. Morphine-CPP acquisition increased the activity of the D1R-ERK-CREB pathway in both the vHip and mPFC. Morphine-CPP reinstatement was associated with the D2R-mediated hyperactive GSK3 via Akt inhibition in the vHip and PFC. Furthermore, integrated D1R-ERK-CREB and D2R-Akt-GSK3 pathways in the vHip-mPFC circuit are required for the acquisition and retrieval of the morphine contextual memory, respectively. Moreover, blockage of D1R or D2R signaling could alleviate normal Hip-dependent spatial memory. These results suggest that D1R and D2R signaling are differentially involved in the acquisition and retrieval of morphine contextual memory, and DA signaling in the vHip-mPFC connection contributes to morphine-associated and normal memory, largely depending on opiate exposure states.

Human Mas-Related G Protein-Coupled Receptors-X1 Induce Chemokine Receptor 2 Expression in Rat Dorsal Root Ganglia Neurons and Release of Chemokine Ligand 2 from the Human LAD-2 Mast Cell Line

PubMed Central

Solinski, Hans Jürgen; Petermann, Franziska; Rothe, Kathrin; Boekhoff, Ingrid; Gudermann, Thomas; Breit, Andreas

2013-01-01

Primate-specific Mas-related G protein-coupled receptors-X1 (MRGPR-X1) are highly enriched in dorsal root ganglia (DRG) neurons and induce acute pain. Herein, we analyzed effects of MRGPR-X1 on serum response factors (SRF) or nuclear factors of activated T cells (NFAT), which control expression of various markers of chronic pain. Using HEK293, DRG neuron-derived F11 cells and cultured rat DRG neurons recombinantly expressing human MRGPR-X1, we found activation of a SRF reporter gene construct and induction of the early growth response protein-1 via extracellular signal-regulated kinases-1/2 known to play a significant role in the development of inflammatory pain. Furthermore, we observed MRGPR-X1-induced up-regulation of the chemokine receptor 2 (CCR2) via NFAT, which is considered as a key event in the onset of neuropathic pain and, so far, has not yet been described for any endogenous neuropeptide. Up-regulation of CCR2 is often associated with increased release of its endogenous agonist chemokine ligand 2 (CCL2). We also found MRGPR-X1-promoted release of CCL2 in a human connective tissue mast cell line endogenously expressing MRGPR-X1. Thus, we provide first evidence to suggest that MRGPR-X1 induce expression of chronic pain markers in DRG neurons and propose a so far unidentified signaling circuit that enhances chemokine signaling by acting on two distinct yet functionally co-operating cell types. Given the important role of chemokine signaling in pain chronification, we propose that interruption of this signaling circuit might be a promising new strategy to alleviate chemokine-promoted pain. PMID:23505557

Intra- and interregional coregulation of opioid genes: broken symmetry in spinal circuits

PubMed Central

Kononenko, Olga; Galatenko, Vladimir; Andersson, Malin; Bazov, Igor; Watanabe, Hiroyuki; Zhou, Xing Wu; Iatsyshyna, Anna; Mityakina, Irina; Yakovleva, Tatiana; Sarkisyan, Daniil; Ponomarev, Igor; Krishtal, Oleg; Marklund, Niklas; Tonevitsky, Alex; Adkins, DeAnna L.; Bakalkin, Georgy

2017-01-01

Regulation of the formation and rewiring of neural circuits by neuropeptides may require coordinated production of these signaling molecules and their receptors that may be established at the transcriptional level. Here, we address this hypothesis by comparing absolute expression levels of opioid peptides with their receptors, the largest neuropeptide family, and by characterizing coexpression (transcriptionally coordinated) patterns of these genes. We demonstrated that expression patterns of opioid genes highly correlate within and across functionally and anatomically different areas. Opioid peptide genes, compared with their receptor genes, are transcribed at much greater absolute levels, which suggests formation of a neuropeptide cloud that covers the receptor-expressed circuits. Surprisingly, we found that both expression levels and the proportion of opioid receptors are strongly lateralized in the spinal cord, interregional coexpression patterns are side specific, and intraregional coexpression profiles are affected differently by left- and right-side unilateral body injury. We propose that opioid genes are regulated as interconnected components of the same molecular system distributed between distinct anatomic regions. The striking feature of this system is its asymmetric coexpression patterns, which suggest side-specific regulation of selective neural circuits by opioid neurohormones.—Kononenko, O., Galatenko, V., Andersson, M., Bazov, I., Watanabe, H., Zhou, X. W., Iatsyshyna, A., Mityakina, I., Yakovleva, T., Sarkisyan, D., Ponomarev, I., Krishtal, O., Marklund, N., Tonevitsky, A., Adkins, D. L., Bakalkin, G. Intra- and interregional coregulation of opioid genes: broken symmetry in spinal circuits. PMID:28122917

Dopamine signaling in reward-related behaviors.

PubMed

Baik, Ja-Hyun

2013-01-01

Dopamine (DA) regulates emotional and motivational behavior through the mesolimbic dopaminergic pathway. Changes in DA mesolimbic neurotransmission have been found to modify behavioral responses to various environmental stimuli associated with reward behaviors. Psychostimulants, drugs of abuse, and natural reward such as food can cause substantial synaptic modifications to the mesolimbic DA system. Recent studies using optogenetics and DREADDs, together with neuron-specific or circuit-specific genetic manipulations have improved our understanding of DA signaling in the reward circuit, and provided a means to identify the neural substrates of complex behaviors such as drug addiction and eating disorders. This review focuses on the role of the DA system in drug addiction and food motivation, with an overview of the role of D1 and D2 receptors in the control of reward-associated behaviors.

Essential Neuroscience in Immunology

PubMed Central

Chavan, Sangeeta S.; Tracey, Kevin J.

2017-01-01

The field of immunology is principally focused on the molecular mechanisms by which hematopoetic cells initiate and maintain innate and adaptive immunity. That cornerstone of attention has been expanded by recent discoveries that neuronal signals occupy a critical regulatory niche in immunity. The discovery is that neuronal circuits operating reflexively regulate innate and adaptive immunity. One particularly well-characterized circuit regulating innate immunity, the inflammatory reflex, is dependent upon action potentials transmitted to the reticuloendothelial system via the vagus and splenic nerves. This field has grown significantly with identification of several other reflexes regulating discrete immune functions. As reviewed here, the delineation of these mechanisms revealed a new understanding of immunity, enabled a first in class clinical trial using bioelectronic devices to inhibit cytokines and inflammation in rheumatoid arthritis patients, and provided a mosaic view of immunity as the integration of hematopoetic and neural responses to infection and injury. PMID:28416717

Essential Neuroscience in Immunology.

PubMed

Chavan, Sangeeta S; Tracey, Kevin J

2017-05-01

The field of immunology is principally focused on the molecular mechanisms by which hematopoietic cells initiate and maintain innate and adaptive immunity. That cornerstone of attention has been expanded by recent discoveries that neuronal signals occupy a critical regulatory niche in immunity. The discovery is that neuronal circuits operating reflexively regulate innate and adaptive immunity. One particularly well-characterized circuit regulating innate immunity, the inflammatory reflex, is dependent upon action potentials transmitted to the reticuloendothelial system via the vagus and splenic nerves. This field has grown significantly with the identification of several other reflexes regulating discrete immune functions. As outlined in this review, the delineation of these mechanisms revealed a new understanding of immunity, enabled a first-in-class clinical trial using bioelectronic devices to inhibit cytokines and inflammation in rheumatoid arthritis patients, and provided a mosaic view of immunity as the integration of hematopoietic and neural responses to infection and injury. Copyright © 2017 by The American Association of Immunologists, Inc.

Design of 5 V DC to 20 V DC switching regulator for power supply module

NASA Astrophysics Data System (ADS)

Azmi, N. A.; Murad, S. A. Z.; Harun, A.; Ismail, R. C.; Isa, M. N. M.; Zulkifeli, M. A.

2017-09-01

This paper presents the design of 5 V to 20 V DC switching regulator for power supply module. A voltage multiplier which consists of cascaded diode-capacitor combination is used in order to obtain a high voltage power supply. Due to power loss that has occurred in a stray of component arrangement, the proposed design employs a pulse width modulation (PWM) controller circuit with an inclusion of a capacitor, diode, and inductor components. The input supply of 5 V DC to LT1618 controller circuit has produced 20.35 V based from simulation results. Meanwhile, the measurement results of 19.36 V are obtained and the feedback signal is required for the purpose of stabilizing the output. The proposed design can reduce the components as well as the PCB size, thus minimizing the overall cost of making a switching regulator for power supply module.

Antagonistic Rgg regulators mediate quorum sensing via competitive DNA binding in Streptococcus pyogenes.

PubMed

Lasarre, Breah; Aggarwal, Chaitanya; Federle, Michael J

2013-01-02

Recent studies have established the fact that multiple members of the Rgg family of transcriptional regulators serve as key components of quorum sensing (QS) pathways that utilize peptides as intercellular signaling molecules. We previously described a novel QS system in Streptococcus pyogenes which utilizes two Rgg-family regulators (Rgg2 and Rgg3) that respond to neighboring signaling peptides (SHP2 and SHP3) to control gene expression and biofilm formation. We have shown that Rgg2 is a transcriptional activator of target genes, whereas Rgg3 represses expression of these genes, and that SHPs function to activate the QS system. The mechanisms by which Rgg proteins regulate both QS-dependent and QS-independent processes remain poorly defined; thus, we sought to further elucidate how Rgg2 and Rgg3 mediate gene regulation. Here we provide evidence that S. pyogenes employs a unique mechanism of direct competition between the antagonistic, peptide-responsive proteins Rgg2 and Rgg3 for binding at target promoters. The highly conserved, shared binding sites for Rgg2 and Rgg3 are located proximal to the -35 nucleotide in the target promoters, and the direct competition between the two regulators results in concentration-dependent, exclusive occupation of the target promoters that can be skewed in favor of Rgg2 in vitro by the presence of SHP. These results suggest that exclusionary binding of target promoters by Rgg3 may prevent Rgg2 binding under SHP-limiting conditions, thereby preventing premature induction of the quorum sensing circuit. Rgg-family transcriptional regulators are widespread among low-G+C Gram-positive bacteria and in many cases contribute to bacterial physiology and virulence. Only recently was it discovered that several Rgg proteins function in cell-to-cell communication (quorum sensing [QS]) via direct interaction with signaling peptides. The mechanism(s) by which Rgg proteins mediate regulation is poorly understood, and further insight into Rgg function is anticipated to be of great importance for the understanding of both regulatory-network architecture and intercellular communication in Rgg-containing species. The results of this study on the Rgg2/3 QS circuit of S. pyogenes demonstrate that DNA binding of target promoters by the activator Rgg2 is directly inhibited by competitive binding by the repressor Rgg3, thereby preventing transcriptional activation of the target genes and premature induction of the QS circuit. This is a unique regulatory mechanism among Rgg proteins and other peptide-responsive QS regulators.

Lessons from sleeping flies: insights from Drosophila melanogaster on the neuronal circuitry and importance of sleep.

PubMed

Potdar, Sheetal; Sheeba, Vasu

2013-06-01

Sleep is a highly conserved behavior whose role is as yet unknown, although it is widely acknowledged as being important. Here we provide an overview of many vital questions regarding this behavior, that have been addressed in recent years using the genetically tractable model organism Drosophila melanogaster in several laboratories around the world. Rest in D. melanogaster has been compared to mammalian sleep and its homeostatic and circadian regulation have been shown to be controlled by intricate neuronal circuitry involving circadian clock neurons, mushroom bodies, and pars intercerebralis, although their exact roles are not entirely clear. We draw attention to the yet unanswered questions and contradictions regarding the nature of the interactions between the brain regions implicated in the control of sleep. Dopamine, octopamine, γ-aminobutyric acid (GABA), and serotonin are the chief neurotransmitters identified as functioning in different limbs of this circuit, either promoting arousal or sleep by modulating membrane excitability of underlying neurons. Some studies have suggested that certain brain areas may contribute towards both sleep and arousal depending on activation of specific subsets of neurons. Signaling pathways implicated in the sleep circuit include cyclic adenosine monophosphate (cAMP) and epidermal growth factor receptor-extracellular signal-regulated kinase (EGFR-ERK) signaling pathways that operate on different neural substrates. Thus, this field of research appears to be on the cusp of many new and exciting findings that may eventually help in understanding how this complex physiological phenomenon is modulated by various neuronal circuits in the brain. Finally, some efforts to approach the "Holy Grail" of why we sleep have been summarized.

Transplantation of prokaryotic two-component signaling pathways into mammalian cells.

PubMed

Hansen, Jonathan; Mailand, Erik; Swaminathan, Krishna Kumar; Schreiber, Joerg; Angelici, Bartolomeo; Benenson, Yaakov

2014-11-04

Signaling pathway engineering is a promising route toward synthetic biological circuits. Histidine-aspartate phosphorelays are thought to have evolved in prokaryotes where they form the basis for two-component signaling. Tyrosine-serine-threonine phosphorelays, exemplified by MAP kinase cascades, are predominant in eukaryotes. Recently, a prokaryotic two-component pathway was implemented in a plant species to sense environmental trinitrotoluene. We reasoned that "transplantation" of two-component pathways into mammalian host could provide an orthogonal and diverse toolkit for a variety of signal processing tasks. Here we report that two-component pathways could be partially reconstituted in mammalian cell culture and used for programmable control of gene expression. To enable this reconstitution, coding sequences of histidine kinase (HK) and response regulator (RR) components were codon-optimized for human cells, whereas the RRs were fused with a transactivation domain. Responsive promoters were furnished by fusing DNA binding sites in front of a minimal promoter. We found that coexpression of HKs and their cognate RRs in cultured mammalian cells is necessary and sufficient to strongly induce gene expression even in the absence of pathways' chemical triggers in the medium. Both loss-of-function and constitutive mutants behaved as expected. We further used the two-component signaling pathways to implement two-input logical AND, NOR, and OR gene regulation. Thus, two-component systems can be applied in different capacities in mammalian cells and their components can be used for large-scale synthetic gene circuits.

Deregulation of Cell Signaling in Cancer

PubMed Central

Giancotti, Filippo G.

2014-01-01

Summary Oncogenic mutations disrupt the regulatory circuits that govern cell function, enabling tumor cells to undergo de-regulated mitogenesis, to resist to proapoptotic insults, and to invade through tissue boundaries. Cancer cell biology has played a crucial role in elucidating the signaling mechanisms by which oncogenic mutations sustain these malignant behaviors and thereby in identifying rational targets for cancer drugs. The efficacy of such targeted therapies illustrate the power of a reductionist approach to the study of cancer. PMID:24561200

Systematic Transfer of Prokaryotic Sensors and Circuits to Mammalian Cells

PubMed Central

2015-01-01

Prokaryotic regulatory proteins respond to diverse signals and represent a rich resource for building synthetic sensors and circuits. The TetR family contains >105 members that use a simple mechanism to respond to stimuli and bind distinct DNA operators. We present a platform that enables the transfer of these regulators to mammalian cells, which is demonstrated using human embryonic kidney (HEK293) and Chinese hamster ovary (CHO) cells. The repressors are modified to include nuclear localization signals (NLS) and responsive promoters are built by incorporating multiple operators. Activators are also constructed by modifying the protein to include a VP16 domain. Together, this approach yields 15 new regulators that demonstrate 19- to 551-fold induction and retain both the low levels of crosstalk in DNA binding specificity observed between the parent regulators in Escherichia coli, as well as their dynamic range of activity. By taking advantage of the DAPG small molecule sensing mediated by the PhlF repressor, we introduce a new inducible system with 50-fold induction and a threshold of 0.9 μM DAPG, which is comparable to the classic Dox-induced TetR system. A set of NOT gates is constructed from the new repressors and their response function quantified. Finally, the Dox- and DAPG- inducible systems and two new activators are used to build a synthetic enhancer (fuzzy AND gate), requiring the coordination of 5 transcription factors organized into two layers. This work introduces a generic approach for the development of mammalian genetic sensors and circuits to populate a toolbox that can be applied to diverse applications from biomanufacturing to living therapeutics. PMID:25360681

Systematic transfer of prokaryotic sensors and circuits to mammalian cells.

PubMed

Stanton, Brynne C; Siciliano, Velia; Ghodasara, Amar; Wroblewska, Liliana; Clancy, Kevin; Trefzer, Axel C; Chesnut, Jonathan D; Weiss, Ron; Voigt, Christopher A

2014-12-19

Prokaryotic regulatory proteins respond to diverse signals and represent a rich resource for building synthetic sensors and circuits. The TetR family contains >10(5) members that use a simple mechanism to respond to stimuli and bind distinct DNA operators. We present a platform that enables the transfer of these regulators to mammalian cells, which is demonstrated using human embryonic kidney (HEK293) and Chinese hamster ovary (CHO) cells. The repressors are modified to include nuclear localization signals (NLS) and responsive promoters are built by incorporating multiple operators. Activators are also constructed by modifying the protein to include a VP16 domain. Together, this approach yields 15 new regulators that demonstrate 19- to 551-fold induction and retain both the low levels of crosstalk in DNA binding specificity observed between the parent regulators in Escherichia coli, as well as their dynamic range of activity. By taking advantage of the DAPG small molecule sensing mediated by the PhlF repressor, we introduce a new inducible system with 50-fold induction and a threshold of 0.9 μM DAPG, which is comparable to the classic Dox-induced TetR system. A set of NOT gates is constructed from the new repressors and their response function quantified. Finally, the Dox- and DAPG- inducible systems and two new activators are used to build a synthetic enhancer (fuzzy AND gate), requiring the coordination of 5 transcription factors organized into two layers. This work introduces a generic approach for the development of mammalian genetic sensors and circuits to populate a toolbox that can be applied to diverse applications from biomanufacturing to living therapeutics.

Hypothalamic Leptin and Ghrelin Signaling as Targets for Improvement in Metabolic Control.

PubMed

Frago, Laura M; Chowen, Julie A

2015-01-01

Metabolic homeostasis requires a tight balance between energy intake and energy expenditure; hence, the physiological circuits implicated in the regulation of energy metabolism must be able to quickly adjust to changes in either side of the equation. Circulating orexigenic and anorexigenic factors, including ghrelin and leptin, are produced in the gastrointestinal tract and adipose tissue, respectively, in relation to an individual's nutritional status. These signals interact with central metabolic circuits to regulate the production and secretion of neuropeptides implicated in the control of appetite and energy expenditure. However, this physiological equilibrium can be perturbed by diverse processes, with weight gain occurring due to a positive energy balance and weight loss taking place if there is a negative energy balance. If a situation of positive energy balance continues for an extended period of time, excess weight is accumulated and this can eventually result in obesity. Obesity has become one of the most important health problems facing the industrialized world, indicating that metabolic equilibrium is frequently disrupted. Understanding how and why this occurs will allow new therapeutical targets to be identified.

MOSFET analog memory circuit achieves long duration signal storage

NASA Technical Reports Server (NTRS)

1966-01-01

Memory circuit maintains the signal voltage at the output of an analog signal amplifier when the input signal is interrupted or removed. The circuit uses MOSFET /Metal Oxide Semiconductor Field Effect Transistor/ devices as voltage-controlled switches, triggered by an external voltage-sensing device.

Origin of bistability underlying mammalian cell cycle entry

PubMed Central

Yao, Guang; Tan, Cheemeng; West, Mike; Nevins, Joseph R; You, Lingchong

2011-01-01

Precise control of cell proliferation is fundamental to tissue homeostasis and differentiation. Mammalian cells commit to proliferation at the restriction point (R-point). It has long been recognized that the R-point is tightly regulated by the Rb–E2F signaling pathway. Our recent work has further demonstrated that this regulation is mediated by a bistable switch mechanism. Nevertheless, the essential regulatory features in the Rb–E2F pathway that create this switching property have not been defined. Here we analyzed a library of gene circuits comprising all possible link combinations in a simplified Rb–E2F network. We identified a minimal circuit that is able to generate robust, resettable bistability. This minimal circuit contains a feed-forward loop coupled with a mutual-inhibition feedback loop, which forms an AND-gate control of the E2F activation. Underscoring its importance, experimental disruption of this circuit abolishes maintenance of the activated E2F state, supporting its importance for the bistability of the Rb–E2F system. Our findings suggested basic design principles for the robust control of the bistable cell cycle entry at the R-point. PMID:21525871

Serotonin homeostasis and serotonin receptors as actors of cortical construction: special attention to the 5-HT3A and 5-HT6 receptor subtypes

PubMed Central

Vitalis, Tania; Ansorge, Mark S.; Dayer, Alexandre G.

2013-01-01

Cortical circuits control higher-order cognitive processes and their function is highly dependent on their structure that emerges during development. The construction of cortical circuits involves the coordinated interplay between different types of cellular processes such as proliferation, migration, and differentiation of neural and glial cell subtypes. Among the multiple factors that regulate the assembly of cortical circuits, 5-HT is an important developmental signal that impacts on a broad diversity of cellular processes. 5-HT is detected at the onset of embryonic telencephalic formation and a variety of serotonergic receptors are dynamically expressed in the embryonic developing cortex in a region and cell-type specific manner. Among these receptors, the ionotropic 5-HT3A receptor and the metabotropic 5-HT6 receptor have recently been identified as novel serotonergic targets regulating different aspects of cortical construction including neuronal migration and dendritic differentiation. In this review, we focus on the developmental impact of serotonergic systems on the construction of cortical circuits and discuss their potential role in programming risk for human psychiatric disorders. PMID:23801939

Full wave modulator-demodulator amplifier apparatus. [for generating rectified output signal

NASA Technical Reports Server (NTRS)

Black, J. M. (Inventor)

1974-01-01

A full-wave modulator-demodulator apparatus is described including an operational amplifier having a first input terminal coupled to a circuit input terminal, and a second input terminal alternately coupled to the circuit input terminal. A circuit is ground by a switching circuit responsive to a phase reference signal and the operational amplifier is alternately switched between a non-inverting mode and an inverting mode. The switching circuit includes three field-effect transistors operatively associated to provide the desired switching function in response to an alternating reference signal of the same frequency as an AC input signal applied to the circuit input terminal.

Bistability in a complementary metal oxide semiconductor inverter circuit.

PubMed

Carroll, Thomas L

2005-09-01

Radiofrequency signals can disrupt the operation of low frequency circuits. A digital inverter circuit would seem to be immune to such disruption, because its output state usually jumps abruptly between 0 and 5 V. Nevertheless, when driven with a high frequency signal, the inverter can have two coexisting stable states (which are not at 0 and 5 V). Slow switching between these states (by changing the rf signal) will produce a low frequency signal. I demonstrate the bistability in a circuit experiment and in a simple model of the circuit.

Type III Neuregulin-1 is required for normal sensorimotor gating, memory related behaviors and cortico-striatal circuit components

PubMed Central

Chen, Ying-Jiun J.; Johnson, Madeleine A.; Lieberman, Michael D.; Goodchild, Rose E.; Schobel, Scott; Lewandowski, Nicole; Rosoklija, Gorazd; Liu, Ruei-Che; Gingrich, Jay A.; Small, Scott; Moore, Holly; Dwork, Andrew J.; Talmage, David A.; Role, Lorna W.

2008-01-01

Neuregulin-1 (Nrg1)/erbB signaling regulates neuronal development, migration, myelination, and synaptic maintenance. The Nrg1 gene is a schizophrenia susceptibility gene. To understand the contribution of Nrg1 signaling to adult brain structure and behaviors, we have studied the regulation of Type III Nrg1 expression and evaluated the effect of decreased expression of the Type III Nrg1 isoforms. Type III Nrg1 is transcribed by a promoter distinct from those for other Nrg1 isoforms and, in the adult brain, is expressed in the medial prefrontal cortex, ventral hippocampus and ventral subiculum, regions involved in the regulation of sensorimotor gating and short term memory. Adult heterozygous mutant mice with a targeted disruption for Type III Nrg1 (Nrg1tm1.1Lwr+/-) have enlarged lateral ventricles and decreased dendritic spine density on subicular pyramidal neurons. MRI imaging of Type III Nrg1 heterozygous mice revealed hypo-function in the medial prefrontal cortex and the hippocampal CA1 and subiculum regions. Type III Nrg1 heterozygous mice also have impaired performance on delayed alternation memory tasks, and deficits in prepulse inhibition (PPI). Chronic nicotine treatment eliminated differences in PPI between Type III Nrg1 heterozygous mice and their wild type littermates. Our findings demonstrate a role of Type III Nrg1-signaling in the maintenance of cortico-striatal components, and in the neural circuits involved in sensorimotor gating and short term memory. PMID:18596162

Biomedically relevant circuit-design strategies in mammalian synthetic biology

PubMed Central

Bacchus, William; Aubel, Dominique; Fussenegger, Martin

2013-01-01

The development and progress in synthetic biology has been remarkable. Although still in its infancy, synthetic biology has achieved much during the past decade. Improvements in genetic circuit design have increased the potential for clinical applicability of synthetic biology research. What began as simple transcriptional gene switches has rapidly developed into a variety of complex regulatory circuits based on the transcriptional, translational and post-translational regulation. Instead of compounds with potential pharmacologic side effects, the inducer molecules now used are metabolites of the human body and even members of native cell signaling pathways. In this review, we address recent progress in mammalian synthetic biology circuit design and focus on how novel designs push synthetic biology toward clinical implementation. Groundbreaking research on the implementation of optogenetics and intercellular communications is addressed, as particularly optogenetics provides unprecedented opportunities for clinical application. Along with an increase in synthetic network complexity, multicellular systems are now being used to provide a platform for next-generation circuit design. PMID:24061539

An intra-amygdala circuit specifically regulates social fear learning

PubMed Central

Twining, Robert C.; Vantrease, Jaime E.; Love, Skyelar; Padival, Mallika; Rosenkranz, J. Amiel

2016-01-01

Adaptive social behavior requires transmission and reception of salient social information. Impairment of this reciprocity is a cardinal symptom of autism. The amygdala is a critical mediator of social behavior and is implicated in social symptoms of autism. Here we found that a specific amygdala circuit, from the lateral nucleus to the medial nucleus (LA-MeA), is required for using social cues to learn about environmental cues that signal imminent threats. Disruption of the LA-MeA circuit impaired valuation of these environmental cues and subsequent ability to use this cue to guide behavior. Rats with impaired social guidance of behavior due to knockout of Nrxn1, an analog to autism-associated genes (NRXN), exhibited marked LA-MeA deficits. Chemogenetic activation of this circuit reversed these impaired social behaviors. These findings identify an amygdala circuit required to guide emotional responses to socially significant cues and identify a novel exploratory target for disorders associated with social impairments. PMID:28114293

49 CFR 236.303 - Control circuits for signals, selection through circuit controller operated by switch points or...

Code of Federal Regulations, 2010 CFR

2010-10-01

... circuit controller operated by switch points or by switch locking mechanism. 236.303 Section 236.303... § 236.303 Control circuits for signals, selection through circuit controller operated by switch points or by switch locking mechanism. The control circuit for each aspect with indication more favorable...

49 CFR 236.303 - Control circuits for signals, selection through circuit controller operated by switch points or...

Code of Federal Regulations, 2012 CFR

2012-10-01

... circuit controller operated by switch points or by switch locking mechanism. 236.303 Section 236.303... § 236.303 Control circuits for signals, selection through circuit controller operated by switch points or by switch locking mechanism. The control circuit for each aspect with indication more favorable...

49 CFR 236.303 - Control circuits for signals, selection through circuit controller operated by switch points or...

Code of Federal Regulations, 2013 CFR

2013-10-01

... circuit controller operated by switch points or by switch locking mechanism. 236.303 Section 236.303... § 236.303 Control circuits for signals, selection through circuit controller operated by switch points or by switch locking mechanism. The control circuit for each aspect with indication more favorable...

49 CFR 236.303 - Control circuits for signals, selection through circuit controller operated by switch points or...

Code of Federal Regulations, 2014 CFR

2014-10-01

... circuit controller operated by switch points or by switch locking mechanism. 236.303 Section 236.303... § 236.303 Control circuits for signals, selection through circuit controller operated by switch points or by switch locking mechanism. The control circuit for each aspect with indication more favorable...

49 CFR 236.303 - Control circuits for signals, selection through circuit controller operated by switch points or...

Code of Federal Regulations, 2011 CFR

2011-10-01

... circuit controller operated by switch points or by switch locking mechanism. 236.303 Section 236.303... § 236.303 Control circuits for signals, selection through circuit controller operated by switch points or by switch locking mechanism. The control circuit for each aspect with indication more favorable...

Parallel circuits control temperature preference in Drosophila during ageing.

PubMed

Shih, Hsiang-Wen; Wu, Chia-Lin; Chang, Sue-Wei; Liu, Tsung-Ho; Lai, Jason Sih-Yu; Fu, Tsai-Feng; Fu, Chien-Chung; Chiang, Ann-Shyn

2015-07-16

The detection of environmental temperature and regulation of body temperature are integral determinants of behaviour for all animals. These functions become less efficient in aged animals, particularly during exposure to cold environments, yet the cellular and molecular mechanisms are not well understood. Here, we identify an age-related change in the temperature preference of adult fruit flies that results from a shift in the relative contributions of two parallel mushroom body (MB) circuits—the β'- and β-systems. The β'-circuit primarily controls cold avoidance through dopamine signalling in young flies, whereas the β-circuit increasingly contributes to cold avoidance as adult flies age. Elevating dopamine levels in β'-afferent neurons of aged flies restores cold sensitivity, suggesting that the alteration of cold avoidance behaviour with ageing is functionally reversible. These results provide a framework for investigating how molecules and individual neural circuits modulate homeostatic alterations during the course of senescence.

Parallel circuits control temperature preference in Drosophila during ageing

PubMed Central

Shih, Hsiang-Wen; Wu, Chia-Lin; Chang, Sue-Wei; Liu, Tsung-Ho; Sih-Yu Lai, Jason; Fu, Tsai-Feng; Fu, Chien-Chung; Chiang, Ann-Shyn

2015-01-01

The detection of environmental temperature and regulation of body temperature are integral determinants of behaviour for all animals. These functions become less efficient in aged animals, particularly during exposure to cold environments, yet the cellular and molecular mechanisms are not well understood. Here, we identify an age-related change in the temperature preference of adult fruit flies that results from a shift in the relative contributions of two parallel mushroom body (MB) circuits—the β′- and β-systems. The β′-circuit primarily controls cold avoidance through dopamine signalling in young flies, whereas the β-circuit increasingly contributes to cold avoidance as adult flies age. Elevating dopamine levels in β′-afferent neurons of aged flies restores cold sensitivity, suggesting that the alteration of cold avoidance behaviour with ageing is functionally reversible. These results provide a framework for investigating how molecules and individual neural circuits modulate homeostatic alterations during the course of senescence. PMID:26178754

Practical applications of current loop signal conditioning

NASA Astrophysics Data System (ADS)

Anderson, Karl F.

1994-10-01

This paper describes a variety of practical application circuits based on the current loop signal conditioning paradigm. Equations defining the circuit response are also provided. The constant current loop is a fundamental signal conditioning circuit concept that can be implemented in a variety of configurations for resistance-based transducers, such as strain gages and resistance temperature devices. The circuit features signal conditioning outputs which are unaffected by extremely large variations in lead wire resistance, direct current frequency response, and inherent linearity with respect to resistance change. Sensitivity of this circuit is double that of a Wheatstone bridge circuit. Electrical output is zero for resistance change equals zero. The same excitation and output sense wires can serve multiple transducers. More application arrangements are possible with constant current loop signal conditioning than with the Wheatstone bridge.

Current loop signal conditioning: Practical applications

NASA Technical Reports Server (NTRS)

Anderson, Karl F.

1995-01-01

This paper describes a variety of practical application circuits based on the current loop signal conditioning paradigm. Equations defining the circuit response are also provided. The constant current loop is a fundamental signal conditioning circuit concept that can be implemented in a variety of configurations for resistance-based transducers, such as strain gages and resistance temperature detectors. The circuit features signal conditioning outputs which are unaffected by extremely large variations in lead wire resistance, direct current frequency response, and inherent linearity with respect to resistance change. Sensitivity of this circuit is double that of a Wheatstone bridge circuit. Electrical output is zero for resistance change equals zero. The same excitation and output sense wires can serve multiple transducers. More application arrangements are possible with constant current loop signal conditioning than with the Wheatstone bridge.

External light activates hair follicle stem cells through eyes via an ipRGC-SCN-sympathetic neural pathway.

PubMed

Fan, Sabrina Mai-Yi; Chang, Yi-Ting; Chen, Chih-Lung; Wang, Wei-Hung; Pan, Ming-Kai; Chen, Wen-Pin; Huang, Wen-Yen; Xu, Zijian; Huang, Hai-En; Chen, Ting; Plikus, Maksim V; Chen, Shih-Kuo; Lin, Sung-Jan

2018-06-29

Changes in external light patterns can alter cell activities in peripheral tissues through slow entrainment of the central clock in suprachiasmatic nucleus (SCN). It remains unclear whether cells in otherwise photo-insensitive tissues can achieve rapid responses to changes in external light. Here we show that light stimulation of animals' eyes results in rapid activation of hair follicle stem cells with prominent hair regeneration. Mechanistically, light signals are interpreted by M1-type intrinsically photosensitive retinal ganglion cells (ipRGCs), which signal to the SCN via melanopsin. Subsequently, efferent sympathetic nerves are immediately activated. Increased norepinephrine release in skin promotes hedgehog signaling to activate hair follicle stem cells. Thus, external light can directly regulate tissue stem cells via an ipRGC-SCN autonomic nervous system circuit. Since activation of sympathetic nerves is not limited to skin, this circuit can also facilitate rapid adaptive responses to external light in other homeostatic tissues.

Fast, high sensitivity dewpoint hygrometer

NASA Technical Reports Server (NTRS)

Hoenk, Michael E. (Inventor)

1998-01-01

A dewpoint/frostpoint hygrometer that uses a surface moisture-sensitive sensor as part of an RF oscillator circuit with feedback control of the sensor temperature to maintain equilibrium at the sensor surface between ambient water vapor and condensed water/ice. The invention is preferably implemented using a surface acoustic wave (SAW) device in an RF oscillator circuit configured to generate a condensation-dependent output signal, a temperature sensor to measure the temperature of the SAW device and to distinguish between condensation-dependent and temperature-dependent signals, a temperature regulating device to control the temperature of the SAW device, and a feedback control system configured to keep the condensation-dependent signal nearly constant over time in the presence of time-varying humidity, corrected for temperature. The effect of this response is to heat or cool the surface moisture-sensitive device, which shifts the equilibrium with respect to evaporation and condensation at the surface of the device. The equilibrium temperature under feedback control is a measure of dewpoint or frostpoint.

Scram signal generator

DOEpatents

Johanson, Edward W.; Simms, Richard

1981-01-01

A scram signal generating circuit for nuclear reactor installations monitors a flow signal representing the flow rate of the liquid sodium coolant which is circulated through the reactor, and initiates reactor shutdown for a rapid variation in the flow signal, indicative of fuel motion. The scram signal generating circuit includes a long-term drift compensation circuit which processes the flow signal and generates an output signal representing the flow rate of the coolant. The output signal remains substantially unchanged for small variations in the flow signal, attributable to long term drift in the flow rate, but a rapid change in the flow signal, indicative of a fast flow variation, causes a corresponding change in the output signal. A comparator circuit compares the output signal with a reference signal, representing a given percentage of the steady state flow rate of the coolant, and generates a scram signal to initiate reactor shutdown when the output signal equals the reference signal.

Scram signal generator

DOEpatents

Johanson, E.W.; Simms, R.

A scram signal generating circuit for nuclear reactor installations monitors a flow signal representing the flow rate of the liquid sodium coolant which is circulated through the reactor, and initiates reactor shutdown for a rapid variation in the flow signal, indicative of fuel motion. The scram signal generating circuit includes a long-term drift compensation circuit which processes the flow signal and generates an output signal representing the flow rate of the coolant. The output signal remains substantially unchanged for small variations in the flow signal, attributable to long term drift in the flow rate, but a rapid change in the flow signal, indicative of a fast flow variation, causes a corresponding change in the output signal. A comparator circuit compares the output signal with a reference signal, representing a given percentage of the steady state flow rate of the coolant, and generates a scram signal to initiate reactor shutdown when the output signal equals the reference signal.

A Cholinergic-Regulated Circuit Coordinates the Maintenance and Bi-Stable States of a Sensory-Motor Behavior during Caenorhabditis elegans Male Copulation

PubMed Central

Liu, Yishi; LeBeouf, Brigitte; Guo, Xiaoyan; Correa, Paola A.; Gualberto, Daisy G.; Lints, Robyn; Garcia, L. Rene

2011-01-01

Penetration of a male copulatory organ into a suitable mate is a conserved and necessary behavioral step for most terrestrial matings; however, the detailed molecular and cellular mechanisms for this distinct social interaction have not been elucidated in any animal. During mating, the Caenorhabditis elegans male cloaca is maintained over the hermaphrodite's vulva as he attempts to insert his copulatory spicules. Rhythmic spicule thrusts cease when insertion is sensed. Circuit components consisting of sensory/motor neurons and sex muscles for these steps have been previously identified, but it was unclear how their outputs are integrated to generate a coordinated behavior pattern. Here, we show that cholinergic signaling between the cloacal sensory/motor neurons and the posterior sex muscles sustains genital contact between the sexes. Simultaneously, via gap junctions, signaling from these muscles is transmitted to the spicule muscles, thus coupling repeated spicule thrusts with vulval contact. To transit from rhythmic to sustained muscle contraction during penetration, the SPC sensory-motor neurons integrate the signal of spicule's position in the vulva with inputs from the hook and cloacal sensilla. The UNC-103 K+ channel maintains a high excitability threshold in the circuit, so that sustained spicule muscle contraction is not stimulated by fewer inputs. We demonstrate that coordination of sensory inputs and motor outputs used to initiate, maintain, self-monitor, and complete an innate behavior is accomplished via the coupling of a few circuit components. PMID:21423722

Differential regulation of polarized synaptic vesicle trafficking and synapse stability in neural circuit rewiring in Caenorhabditis elegans

PubMed Central

Kurup, Naina; Kono, Karina

2017-01-01

Neural circuits are dynamic, with activity-dependent changes in synapse density and connectivity peaking during different phases of animal development. In C. elegans, young larvae form mature motor circuits through a dramatic switch in GABAergic neuron connectivity, by concomitant elimination of existing synapses and formation of new synapses that are maintained throughout adulthood. We have previously shown that an increase in microtubule dynamics during motor circuit rewiring facilitates new synapse formation. Here, we further investigate cellular control of circuit rewiring through the analysis of mutants obtained in a forward genetic screen. Using live imaging, we characterize novel mutations that alter cargo binding in the dynein motor complex and enhance anterograde synaptic vesicle movement during remodeling, providing in vivo evidence for the tug-of-war between kinesin and dynein in fast axonal transport. We also find that a casein kinase homolog, TTBK-3, inhibits stabilization of nascent synapses in their new locations, a previously unexplored facet of structural plasticity of synapses. Our study delineates temporally distinct signaling pathways that are required for effective neural circuit refinement. PMID:28636662

Synthesizing genetic sequential logic circuit with clock pulse generator.

PubMed

Chuang, Chia-Hua; Lin, Chun-Liang

2014-05-28

Rhythmic clock widely occurs in biological systems which controls several aspects of cell physiology. For the different cell types, it is supplied with various rhythmic frequencies. How to synthesize a specific clock signal is a preliminary but a necessary step to further development of a biological computer in the future. This paper presents a genetic sequential logic circuit with a clock pulse generator based on a synthesized genetic oscillator, which generates a consecutive clock signal whose frequency is an inverse integer multiple to that of the genetic oscillator. An analogous electronic waveform-shaping circuit is constructed by a series of genetic buffers to shape logic high/low levels of an oscillation input in a basic sinusoidal cycle and generate a pulse-width-modulated (PWM) output with various duty cycles. By controlling the threshold level of the genetic buffer, a genetic clock pulse signal with its frequency consistent to the genetic oscillator is synthesized. A synchronous genetic counter circuit based on the topology of the digital sequential logic circuit is triggered by the clock pulse to synthesize the clock signal with an inverse multiple frequency to the genetic oscillator. The function acts like a frequency divider in electronic circuits which plays a key role in the sequential logic circuit with specific operational frequency. A cascaded genetic logic circuit generating clock pulse signals is proposed. Based on analogous implement of digital sequential logic circuits, genetic sequential logic circuits can be constructed by the proposed approach to generate various clock signals from an oscillation signal.

Adaptive gain and filtering circuit for a sound reproduction system

NASA Technical Reports Server (NTRS)

Engebretson, A. Maynard (Inventor); O'Connell, Michael P. (Inventor)

1998-01-01

Adaptive compressive gain and level dependent spectral shaping circuitry for a hearing aid include a microphone to produce an input signal and a plurality of channels connected to a common circuit output. Each channel has a preset frequency response. Each channel includes a filter with a preset frequency response to receive the input signal and to produce a filtered signal, a channel amplifier to amplify the filtered signal to produce a channel output signal, a threshold register to establish a channel threshold level, and a gain circuit. The gain circuit increases the gain of the channel amplifier when the channel output signal falls below the channel threshold level and decreases the gain of the channel amplifier when the channel output signal rises above the channel threshold level. A transducer produces sound in response to the signal passed by the common circuit output.

Thyroid Hormone Acts Locally to Increase Neurogenesis, Neuronal Differentiation, and Dendritic Arbor Elaboration in the Tadpole Visual System

PubMed Central

Thompson, Christopher K.

2016-01-01

Thyroid hormone (TH) regulates many cellular events underlying perinatal brain development in vertebrates. Whether and how TH regulates brain development when neural circuits are first forming is less clear. Furthermore, although the molecular mechanisms that impose spatiotemporal constraints on TH action in the brain have been described, the effects of local TH signaling are poorly understood. We determined the effects of manipulating TH signaling on development of the optic tectum in stage 46–49 Xenopus laevis tadpoles. Global TH treatment caused large-scale morphological effects in tadpoles, including changes in brain morphology and increased tectal cell proliferation. Either increasing or decreasing endogenous TH signaling in tectum, by combining targeted DIO3 knockdown and methimazole, led to corresponding changes in tectal cell proliferation. Local increases in TH, accomplished by injecting suspensions of tri-iodothyronine (T3) in coconut oil into the midbrain ventricle or into the eye, selectively increased tectal or retinal cell proliferation, respectively. In vivo time-lapse imaging demonstrated that local TH first increased tectal progenitor cell proliferation, expanding the progenitor pool, and subsequently increased neuronal differentiation. Local T3 also dramatically increased dendritic arbor growth in neurons that had already reached a growth plateau. The time-lapse data indicate that the same cells are differentially sensitive to T3 at different time points. Finally, TH increased expression of genes pertaining to proliferation and neuronal differentiation. These experiments indicate that endogenous TH locally regulates neurogenesis at developmental stages relevant to circuit assembly by affecting cell proliferation and differentiation and by acting on neurons to increase dendritic arbor elaboration. SIGNIFICANCE STATEMENT Thyroid hormone (TH) is a critical regulator of perinatal brain development in vertebrates. Abnormal TH signaling in early pregnancy is associated with significant cognitive deficits in humans; however, it is difficult to probe the function of TH in early brain development in mammals because of the inaccessibility of the fetal brain in the uterine environment and the challenge of disambiguating maternal versus fetal contributions of TH. The external development of tadpoles allows manipulation and direct observation of the molecular and cellular mechanisms underlying TH's effects on brain development in ways not possible in mammals. We find that endogenous TH locally regulates neurogenesis at developmental stages relevant to circuit assembly by affecting neural progenitor cell proliferation and differentiation and by acting on neurons to enhance dendritic arbor elaboration. PMID:27707971

Transient-Switch-Signal Suppressor

NASA Technical Reports Server (NTRS)

Bozeman, Richard J., Jr.

1995-01-01

Circuit delays transmission of switch-opening or switch-closing signal until after preset suppression time. Used to prevent transmission of undesired momentary switch signal. Basic mode of operation simple. Beginning of switch signal initiates timing sequence. If switch signal persists after preset suppression time, circuit transmits switch signal to external circuitry. If switch signal no longer present after suppression time, switch signal deemed transient, and circuit does not pass signal on to external circuitry, as though no transient switch signal. Suppression time preset at value large enough to allow for damping of underlying pressure wave or other mechanical transient.

Integrating Neural Circuits Controlling Female Sexual Behavior.

PubMed

Micevych, Paul E; Meisel, Robert L

2017-01-01

The hypothalamus is most often associated with innate behaviors such as is hunger, thirst and sex. While the expression of these behaviors important for survival of the individual or the species is nested within the hypothalamus, the desire (i.e., motivation) for them is centered within the mesolimbic reward circuitry. In this review, we will use female sexual behavior as a model to examine the interaction of these circuits. We will examine the evidence for a hypothalamic circuit that regulates consummatory aspects of reproductive behavior, i.e., lordosis behavior, a measure of sexual receptivity that involves estradiol membrane-initiated signaling in the arcuate nucleus (ARH), activating β-endorphin projections to the medial preoptic nucleus (MPN), which in turn modulate ventromedial hypothalamic nucleus (VMH) activity-the common output from the hypothalamus. Estradiol modulates not only a series of neuropeptides, transmitters and receptors but induces dendritic spines that are for estrogenic induction of lordosis behavior. Simultaneously, in the nucleus accumbens of the mesolimbic system, the mating experience produces long term changes in dopamine signaling and structure. Sexual experience sensitizes the response of nucleus accumbens neurons to dopamine signaling through the induction of a long lasting early immediate gene. While estrogen alone increases spines in the ARH, sexual experience increases dendritic spine density in the nucleus accumbens. These two circuits appear to converge onto the medial preoptic area where there is a reciprocal influence of motivational circuits on consummatory behavior and vice versa . While it has not been formally demonstrated in the human, such circuitry is generally highly conserved and thus, understanding the anatomy, neurochemistry and physiology can provide useful insight into the motivation for sexual behavior and other innate behaviors in humans.

Integrating Neural Circuits Controlling Female Sexual Behavior

PubMed Central

Micevych, Paul E.; Meisel, Robert L.

2017-01-01

The hypothalamus is most often associated with innate behaviors such as is hunger, thirst and sex. While the expression of these behaviors important for survival of the individual or the species is nested within the hypothalamus, the desire (i.e., motivation) for them is centered within the mesolimbic reward circuitry. In this review, we will use female sexual behavior as a model to examine the interaction of these circuits. We will examine the evidence for a hypothalamic circuit that regulates consummatory aspects of reproductive behavior, i.e., lordosis behavior, a measure of sexual receptivity that involves estradiol membrane-initiated signaling in the arcuate nucleus (ARH), activating β-endorphin projections to the medial preoptic nucleus (MPN), which in turn modulate ventromedial hypothalamic nucleus (VMH) activity—the common output from the hypothalamus. Estradiol modulates not only a series of neuropeptides, transmitters and receptors but induces dendritic spines that are for estrogenic induction of lordosis behavior. Simultaneously, in the nucleus accumbens of the mesolimbic system, the mating experience produces long term changes in dopamine signaling and structure. Sexual experience sensitizes the response of nucleus accumbens neurons to dopamine signaling through the induction of a long lasting early immediate gene. While estrogen alone increases spines in the ARH, sexual experience increases dendritic spine density in the nucleus accumbens. These two circuits appear to converge onto the medial preoptic area where there is a reciprocal influence of motivational circuits on consummatory behavior and vice versa. While it has not been formally demonstrated in the human, such circuitry is generally highly conserved and thus, understanding the anatomy, neurochemistry and physiology can provide useful insight into the motivation for sexual behavior and other innate behaviors in humans. PMID:28642689

Hunger and thirst interact to regulate ingestive behavior in flies and mammals.

PubMed

Jourjine, Nicholas

2017-05-01

In animals, nervous systems regulate the ingestion of food and water in a manner that reflects internal metabolic need. While the coordination of these two ingestive behaviors is essential for homeostasis, it has been unclear how internal signals of hunger and thirst interact to effectively coordinate food and water ingestion. In the last year, work in insects and mammals has begun to elucidate some of these interactions. As reviewed here, these studies have identified novel molecular and neural mechanisms that coordinate the regulation of food and water ingestion behaviors. These mechanisms include peptide signals that modulate neural circuits for both thirst and hunger, neurons that regulate both food and water ingestion, and neurons that integrate sensory information about both food and water in the external world. These studies argue that a deeper understanding of hunger and thirst will require closer examination of how these two biological drives interact. © 2017 WILEY Periodicals, Inc.

Audio distribution and Monitoring Circuit

NASA Technical Reports Server (NTRS)

Kirkland, J. M.

1983-01-01

Versatile circuit accepts and distributes TV audio signals. Three-meter audio distribution and monitoring circuit provides flexibility in monitoring, mixing, and distributing audio inputs and outputs at various signal and impedance levels. Program material is simultaneously monitored on three channels, or single-channel version built to monitor transmitted or received signal levels, drive speakers, interface to building communications, and drive long-line circuits.

TV Trouble-Shooting Manual. Volumes 9-10. Part 4: Chroma-Signal Reproduction Circuit. Student and Instructor's Manuals.

ERIC Educational Resources Information Center

Mukai, Masaaki; Kobayashi, Ryozo

These volumes are, respectively, the self-instructional student manual and the teacher manual that cover the fourth set of training topics in this course. Both contain identical information on the chroma signal reproduction circuit, including a block diagram of a chroma signal reproduction circuit and sections on the bandpass amplifier circuit,…

Magnetic susceptibility well-logging unit with single power supply thermoregulation system

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

Seeley, R. L.

1985-11-05

The magnetic susceptibility well-logging unit with single power supply thermoregulation system provides power from a single surface power supply over a well-logging cable to an integrated circuit voltage regulator system downhole. This voltage regulator system supplies regulated voltages to a temperature control system and also to a Maxwell bridge sensing unit which includes the solenoid of a magnetic susceptibility probe. The temperature control system is provided with power from the voltage regulator system and operates to permit one of several predetermined temperatures to be chosen, and then operates to maintain the solenoid of a magnetic susceptibility probe at this chosenmore » temperature. The temperature control system responds to a temperature sensor mounted upon the probe solenoid to cause resistance heaters concentrically spaced from the probe solenoid to maintain the chosen temperature. A second temperature sensor on the probe solenoid provides a temperature signal to a temperature transmitting unit, which initially converts the sensed temperature to a representative voltage. This voltage is then converted to a representative current signal which is transmitted by current telemetry over the well logging cable to a surface electronic unit which then reconverts the current signal to a voltage signal.« less

Addiction to the IGF2-ID1-IGF2 circuit for maintenance of the breast cancer stem-like cells

PubMed Central

Tominaga, K; Shimamura, T; Kimura, N; Murayama, T; Matsubara, D; Kanauchi, H; Niida, A; Shimizu, S; Nishioka, K; Tsuji, E-i; Yano, M; Sugano, S; Shimono, Y; Ishii, H; Saya, H; Mori, M; Akashi, K; Tada, K-i; Ogawa, T; Tojo, A; Miyano, S; Gotoh, N

2017-01-01

The transcription factor nuclear factor-κB (NF-κB) has important roles for tumorigenesis, but how it regulates cancer stem cells (CSCs) remains largely unclear. We identified insulin-like growth factor 2 (IGF2) is a key target of NF-κB activated by HER2/HER3 signaling to form tumor spheres in breast cancer cells. The IGF2 receptor, IGF1 R, was expressed at high levels in CSC-enriched populations in primary breast cancer cells. Moreover, IGF2-PI3K (IGF2-phosphatidyl inositol 3 kinase) signaling induced expression of a stemness transcription factor, inhibitor of DNA-binding 1 (ID1), and IGF2 itself. ID1 knockdown greatly reduced IGF2 expression, and tumor sphere formation. Finally, treatment with anti-IGF1/2 antibodies blocked tumorigenesis derived from the IGF1Rhigh CSC-enriched population in a patient-derived xenograft model. Thus, NF-κB may trigger IGF2-ID1-IGF2-positive feedback circuits that allow cancer stem-like cells to appear. Then, they may become addicted to the circuits. As the circuits are the Achilles' heels of CSCs, it will be critical to break them for eradication of CSCs. PMID:27546618

Large Signal Modeling and Analysis of the GaAs MESFET.

DTIC Science & Technology

1986-07-09

various dimensions and physical parameters. A powerful computer aided design system can be developed by automating the circuit element and parameter...circuit model of the GaAs MESFET to aid in the designs of microwave MESFET circuits. The circuit elements of this model are obtained either directly...34. -. ’ Abstract The purpose of this work is to develop a large signal signal lumped circuit model of the GaAs MESFET to aid In the designs of microwave MESFET

Synthesizing genetic sequential logic circuit with clock pulse generator

PubMed Central

2014-01-01

Background Rhythmic clock widely occurs in biological systems which controls several aspects of cell physiology. For the different cell types, it is supplied with various rhythmic frequencies. How to synthesize a specific clock signal is a preliminary but a necessary step to further development of a biological computer in the future. Results This paper presents a genetic sequential logic circuit with a clock pulse generator based on a synthesized genetic oscillator, which generates a consecutive clock signal whose frequency is an inverse integer multiple to that of the genetic oscillator. An analogous electronic waveform-shaping circuit is constructed by a series of genetic buffers to shape logic high/low levels of an oscillation input in a basic sinusoidal cycle and generate a pulse-width-modulated (PWM) output with various duty cycles. By controlling the threshold level of the genetic buffer, a genetic clock pulse signal with its frequency consistent to the genetic oscillator is synthesized. A synchronous genetic counter circuit based on the topology of the digital sequential logic circuit is triggered by the clock pulse to synthesize the clock signal with an inverse multiple frequency to the genetic oscillator. The function acts like a frequency divider in electronic circuits which plays a key role in the sequential logic circuit with specific operational frequency. Conclusions A cascaded genetic logic circuit generating clock pulse signals is proposed. Based on analogous implement of digital sequential logic circuits, genetic sequential logic circuits can be constructed by the proposed approach to generate various clock signals from an oscillation signal. PMID:24884665

Deficiency of leptin receptor in myeloid cells disrupts hypothalamic metabolic circuits and causes body weight increase.

PubMed

Gao, Yuanqing; Vidal-Itriago, Andrés; Milanova, Irina; Korpel, Nikita L; Kalsbeek, Martin J; Tom, Robby Zachariah; Kalsbeek, Andries; Hofmann, Susanna M; Yi, Chun-Xia

2018-01-01

Leptin is a cytokine produced by adipose tissue that acts mainly on the hypothalamus to regulate appetite and energy homeostasis. Previous studies revealed that the leptin receptor is expressed not only in neurons, but also in glial cells. Microglia are resident immune cells in the brain that play an essential role in immune defense and neural network development. Previously we reported that microglial morphology and cytokine production are changed in the leptin receptor deficient db/db mouse, suggesting that leptin's central effects on metabolic control might involve signaling through microglia. In the current study, we aimed to uncover the role of leptin signaling in microglia in systemic metabolic control. We generated a mouse model with leptin receptor deficiency, specifically in the myeloid cells, to determine the role of microglial leptin signaling in the development of metabolic disease and to investigate microglial functions. We discovered that these mice have increased body weight with hyperphagia. In the hypothalamus, pro-opiomelanocortin neuron numbers in the arcuate nucleus (ARC) and α-MSH projections from the ARC to the paraventricular nucleus (PVN) decreased, which was accompanied by the presence of less ramified microglia with impaired phagocytic capacity in the PVN. Myeloid cell leptin receptor deficient mice partially replicate the db/db phenotype. Leptin signaling in hypothalamic microglia is important for microglial function and a correct formation of the hypothalamic neuronal circuit regulating metabolism. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

An evaluation of the Intel 2920 digital signal processing integrated circuit

NASA Technical Reports Server (NTRS)

Heller, J.

1981-01-01

The circuit consists of a digital to analog converter, accumulator, read write memory and UV erasable read only memory. The circuit can convert an analog signal to a digital representation, perform mathematical operations on the digital signal and subsequently convert the digital signal to an analog output. Development software tailored for programming the 2920 is presented.

Built-in-test by signature inspection (bitsi)

DOEpatents

Bergeson, Gary C.; Morneau, Richard A.

1991-01-01

A system and method for fault detection for electronic circuits. A stimulus generator sends a signal to the input of the circuit under test. Signature inspection logic compares the resultant signal from test nodes on the circuit to an expected signal. If the signals do not match, the signature inspection logic sends a signal to the control logic for indication of fault detection in the circuit. A data input multiplexer between the test nodes of the circuit under test and the signature inspection logic can provide for identification of the specific node at fault by the signature inspection logic. Control logic responsive to the signature inspection logic conveys information about fault detection for use in determining the condition of the circuit. When used in conjunction with a system test controller, the built-in test by signature inspection system and method can be used to poll a plurality of circuits automatically and continuous for faults and record the results of such polling in the system test controller.

Nerve Growth Factor Regulates Transient Receptor Potential Vanilloid 2 via Extracellular Signal-Regulated Kinase Signaling To Enhance Neurite Outgrowth in Developing Neurons

PubMed Central

Cohen, Matthew R.; Johnson, William M.; Pilat, Jennifer M.; Kiselar, Janna; DeFrancesco-Lisowitz, Alicia; Zigmond, Richard E.

2015-01-01

Neurite outgrowth is key to the formation of functional circuits during neuronal development. Neurotrophins, including nerve growth factor (NGF), increase neurite outgrowth in part by altering the function and expression of Ca2+-permeable cation channels. Here we report that transient receptor potential vanilloid 2 (TRPV2) is an intracellular Ca2+-permeable TRPV channel upregulated by NGF via the mitogen-activated protein kinase (MAPK) signaling pathway to augment neurite outgrowth. TRPV2 colocalized with Rab7, a late endosome protein, in addition to TrkA and activated extracellular signal-regulated kinase (ERK) in neurites, indicating that the channel is closely associated with signaling endosomes. In line with these results, we showed that TRPV2 acts as an ERK substrate and identified the motifs necessary for phosphorylation of TRPV2 by ERK. Furthermore, neurite length, TRPV2 expression, and TRPV2-mediated Ca2+ signals were reduced by mutagenesis of these key ERK phosphorylation sites. Based on these findings, we identified a previously uncharacterized mechanism by which ERK controls TRPV2-mediated Ca2+ signals in developing neurons and further establish TRPV2 as a critical intracellular ion channel in neuronal function. PMID:26416880

Fast-synchronizing high-fidelity spread-spectrum receiver

DOEpatents

Moore, Michael Roy; Smith, Stephen Fulton; Emery, Michael Steven

2004-06-01

A fast-synchronizing receiver having a circuit including an equalizer configured for manipulating an analog signal; a detector in communication with the equalizer; a filter in communication with the detector; an oscillator in communication with the filter; a gate for receiving the manipulated signal; a circuit portion for synchronizing and tracking the manipulated signal; a summing circuit in communication with the circuit portion; and an output gate.

The Role of Glia in Sleep Regulation and Function.

PubMed

Frank, Marcos G

2018-01-28

The cellular mechanisms governing the expression, regulation, and function of sleep are not entirely understood. The traditional view is that these mechanisms are neuronal. An alternative view is that glial brain cells may play important roles in these processes. Their ubiquity in the central nervous system makes them well positioned to modulate neuronal circuits that gate sleep and wake. Their ability to respond to chemical neuronal signals suggests that they form feedback loops with neurons that may globally regulate neuronal activity. Their potential role in detoxifying the brain, regulating neuronal metabolism, and promoting synaptic plasticity raises the intriguing possibility that glia mediate important functions ascribed to sleep.

Shielded multi-stage EMI noise filter

DOEpatents

Kisner, Roger Allen; Fugate, David Lee

2016-11-08

Electromagnetic interference (EMI) noise filter embodiments and methods for filtering are provided herein. EMI noise filters include multiple signal exclusion enclosures. The multiple signal exclusion enclosures contain filter circuit stages. The signal exclusion enclosures can attenuate noise generated external to the enclosures and/or isolate noise currents generated by the corresponding filter circuits within the enclosures. In certain embodiments, an output of one filter circuit stage is connected to an input of the next filter circuit stage. The multiple signal exclusion enclosures can be chambers formed using conductive partitions to divide an outer signal exclusion enclosure. EMI noise filters can also include mechanisms to maintain the components of the filter circuit stages at a consistent temperature. For example, a metal base plate can distribute heat among filter components, and an insulating material can be positioned inside signal exclusion enclosures.

An Investigative Redesign of the ECG and EMG Signal Conditioning Circuits for Two-fault Tolerance and Circuit Improvement

NASA Technical Reports Server (NTRS)

Obrien, Edward M.

1991-01-01

An investigation was undertaken to make the elctrocardiography (ECG) and the electromyography (EMG) signal conditioning circuits two-fault tolerant and to update the circuitry. The present signal conditioning circuits provide at least one level of subject protection against electrical shock hazard but at a level of 100 micro-A (for voltages of up to 200 V). However, it is necessary to provide catastrophic fault tolerance protection for the astronauts and to provide protection at a current level of less that 100 micro-A. For this study, protection at the 10 micro-A level was sought. This is the generally accepted value below which no possibility of microshock exists. Only the possibility of macroshock exists in the case of the signal conditioners. However, this extra amount of protection is desirable. The initial part deals with current limiter circuits followed by an investigation into the signal conditioner specifications and circuit design.

Adaptive sequential controller

DOEpatents

El-Sharkawi, Mohamed A.; Xing, Jian; Butler, Nicholas G.; Rodriguez, Alonso

1994-01-01

An adaptive sequential controller (50/50') for controlling a circuit breaker (52) or other switching device to substantially eliminate transients on a distribution line caused by closing and opening the circuit breaker. The device adaptively compensates for changes in the response time of the circuit breaker due to aging and environmental effects. A potential transformer (70) provides a reference signal corresponding to the zero crossing of the voltage waveform, and a phase shift comparator circuit (96) compares the reference signal to the time at which any transient was produced when the circuit breaker closed, producing a signal indicative of the adaptive adjustment that should be made. Similarly, in controlling the opening of the circuit breaker, a current transformer (88) provides a reference signal that is compared against the time at which any transient is detected when the circuit breaker last opened. An adaptive adjustment circuit (102) produces a compensation time that is appropriately modified to account for changes in the circuit breaker response, including the effect of ambient conditions and aging. When next opened or closed, the circuit breaker is activated at an appropriately compensated time, so that it closes when the voltage crosses zero and opens when the current crosses zero, minimizing any transients on the distribution line. Phase angle can be used to control the opening of the circuit breaker relative to the reference signal provided by the potential transformer.

Charge regulation circuit

DOEpatents

Ball, Don G.

1992-01-01

A charge regulation circuit provides regulation of an unregulated voltage supply in the range of 0.01%. The charge regulation circuit is utilized in a preferred embodiment in providing regulated voltage for controlling the operation of a laser.

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

Alderfer, R.R.; Futa, P.W.

This patent describes a fuel system for an engine having a filter through which fuel from a pump passes to a regulator in response to an operator input. The regulator controls the flow of fuel presented to a combustion chamber in the engine, the regulator having a feedback apparatus to provide an operator with a signal indicative of the fuel supplied to the combustion chamber. It comprises: bypass means having a housing with a chamber therein, the chamber having an entrance port connected to the pump and an exit port connected to the regulator; piston means located in the chambermore » for separating the entrance port from the exit port, the piston having a face with a projection extending therefrom; stop means located in the chamber; resilient means located is the chamber for urging the piston means toward the stop means to prevent the flow of fuel from the pump through the housing to the regulator; and indicator means having a body retained in the housing with a first end which extends through the housing into the from a full-open position at which the closed circuit is fully opened to a full-closed position at which the closed circuit is fully blocked; ratio detecting means which detects the speed reduction ratio to find if the speed reduction ratio becomes substantially 1; and valve position detecting means which detects position of the direct clutch valve to find if the direct clutch valve is moved to a slight-open position at which the closed circuit is slightly opened.« less

Waveshaping electronic circuit

NASA Technical Reports Server (NTRS)

Harper, T. P.

1971-01-01

Circuit provides output signal with sinusoidal function in response to bipolar transition of input signal. Instantaneous transition shapes into linear rate of change and linear rate of change shapes into sinusoidal rate of change. Circuit contains only active components; therefore, compatibility with integrated circuit techniques is assured.

Ripple gate drive circuit for fast operation of series connected IGBTs

DOEpatents

Rockot, Joseph H.; Murray, Thomas W.; Bass, Kevin C.

2005-09-20

A ripple gate drive circuit includes a plurality of transistors having their power terminals connected in series across an electrical potential. A plurality of control circuits, each associated with one of the transistors, is provided. Each control circuit is responsive to a control signal and an optical signal received from at least one other control circuit for controlling the conduction of electrical current through the power terminals of the associated transistor. The control circuits are responsive to a first state of the control circuit for causing each transistor in series to turn on sequentially and responsive to a second state of the control signal for causing each transistor in series to turn off sequentially.

Instrument For Simulation Of Piezoelectric Transducers

NASA Technical Reports Server (NTRS)

Mcnichol, Randal S.

1996-01-01

Electronic instrument designed to simulate dynamic output of integrated-circuit piezoelectric acceleration or pressure transducer. Operates in conjunction with external signal-conditioning circuit, generating square-wave signal of known amplitude for use in calibrating signal-conditioning circuit. Instrument also useful as special-purpose square-wave generator in other applications.

Electronic circuit detects left ventricular ejection events in cardiovascular system

NASA Technical Reports Server (NTRS)

Gebben, V. D.; Webb, J. A., Jr.

1972-01-01

Electronic circuit processes arterial blood pressure waveform to produce discrete signals that coincide with beginning and end of left ventricular ejection. Output signals provide timing signals for computers that monitor cardiovascular systems. Circuit operates reliably for heart rates between 50 and 200 beats per minute.

Tags, wireless communication systems, tag communication methods, and wireless communications methods

DOEpatents

Scott,; Jeff W. , Pratt; Richard, M [Richland, WA

2006-09-12

Tags, wireless communication systems, tag communication methods, and wireless communications methods are described. In one aspect, a tag includes a plurality of antennas configured to receive a plurality of first wireless communication signals comprising data from a reader, a plurality of rectifying circuits coupled with. respective individual ones of the antennas and configured to provide rectified signals corresponding to the first wireless communication signals, wherein the rectified signals are combined to produce a composite signal, an adaptive reference circuit configured to vary a reference signal responsive to the composite signal, a comparator coupled with the adaptive reference circuit and the rectifying circuits and configured to compare the composite signal with respect to the reference signal and to output the data responsive to the comparison, and processing circuitry configured to receive the data from the comparator and to process the data.

Genes, Circuits, and Precision Therapies for Autism and Related Neurodevelopmental Disorders

PubMed Central

2016-01-01

Research in genetics of neurodevelopmental disorders such as autism suggests that several hundred genes are likely risk factors for these disorders. This heterogeneity presents a challenge and an opportunity at the same time. While the exact identity of many of the genes remains to be discovered, genes identified to date encode for proteins that play roles in certain conserved pathways: protein synthesis, transcriptional/epigenetic regulation and synaptic signaling. Next generation of research in neurodevelopmental disorders needs to address the neural circuitry underlying the behavioral symptoms and co-morbidities, the cell types playing critical roles in these circuits and common intercellular signaling pathways that link diverse genes. Results from clinical trials have been mixed so far. Only when we are able to leverage the heterogeneity of neurodevelopmental disorders into precision medicine, will the mechanism-based therapeutics for these disorders start to unlock success. PMID:26472761

Air/fuel ratio control system for internal combustion engine having rotary valve and step motor

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

Saito, M.

A system for feedback control of the air/fuel mixing ratio in an internal combustion engine equipped with a carburetor. The control system has an air/fuel ratio detector of a gas sensor type which provides a feedback signal to a control circuit and a rotary valve which is operated by a stepping motor responsive to a control pulse signal produced by the control circuit to regulate the fuel feed rate so as to nullify a deviation of the detected actual air/fuel ratio from a preset air/fuel ratio. The control system may include two auxiliary air-admitting passages respectively connected to a mainmore » fuel passage and a slow fuel passage in the carburetor, and in this case the single rotary valve is designed and arranged so as to simultaneously control the admission of air into both of the two auxiliary air-admitting passages.« less

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.

Bidirectional amplifier

DOEpatents

Wright, James T.

1986-01-01

A bilateral circuit is operable for transmitting signals in two directions without generation of ringing due to feedback caused by the insertion of the circuit. The circuit may include gain for each of the signals to provide a bidirectional amplifier. The signals are passed through two separate paths, with a unidirectional amplifier in each path. A controlled sampling device is provided in each path for sampling the two signals. Any feedback loop between the two signals is disrupted by providing a phase displacement between the control signals for the two sampling devices.

Bidirectional amplifier

DOEpatents

Wright, J.T.

1984-02-02

A bilateral circuit is operable for transmitting signals in two directions without generation of ringing due to feedback caused by the insertion of the circuit. The circuit may include gain for each of the signals to provide a bidirectional amplifier. The signals are passed through two separate paths, with a unidirectional amplifier in each path. A controlled sampling device is provided in each path for sampling the two signals. Any feedback loop between the two signals is disrupted by providing a phase displacement between the control signals for the two sampling devices.

THE OXYTOCIN-BONE AXIS

PubMed Central

Colaianni, G.; Tamma, R.; Di Benedetto, A.; Yuen, T.; Sun, L.; Zaidi, M.; Zallone, A.

2014-01-01

We recently demonstrated a direct action of oxytocin (OT) on skeletal homeostasis mainly mediated through stimulation of osteoblasts (OBs) formation and through the reciprocal modulation of osteoclast (OCs) formation and function. Thus, mice lacking the hormone or its receptor develop a low turnover osteoporosis that worsens with age in both sexes. The skeleton of OT and OT receptor (Oxtr) null mice display a pronounced decrease in vertebral and femoral trabecular volume. At cellular level OBs from OT−/− and Oxtr−/− mice exhibit lower mineralization activity and, at mRNA level, all master genes for osteoblast differentiation are down regulated. Moreover, OT has dual effects on OCs: it increases osteoclast formation both directly, by activating NF-kB and MAP kinase signaling, and indirectly, through the up-regulation of RANK-L synthesis by OBs. On the other hand, it inhibits bone resorption by triggering cytosolic Ca2+ release and nitric oxide synthesis in mature OCs. OT is locally produced by osteoblasts acting as paracrine-autocrine regulator of bone formation modulated by estrogens. The estrogen signal involved in this feed forward circuit is non genomic, since it requires an intact MAPK kinase signal transduction pathway, instead of the classical nuclear translocation of estrogen receptor. The ability of estrogen to increase bone mass in vivo is to an extent OTR-dependent. Thus Oxtr−/− mice injected 17β-estradiol did not show any effects on bone formation parameters, while the same treatment increases trabecular and cortical bone in wild type mice. An intact OT autocrine-paracrine circuit seems to be essential for optimal skeletal remodeling. PMID:24219627

The design of preamplifier and ADC circuit base on weak e-optical signal

NASA Astrophysics Data System (ADS)

Fen, Leng; Ying-ping, Yang; Ya-nan, Yu; Xiao-ying, Xu

2011-02-01

Combined with the demand of the process of weak e-optical signal in QPD detection system, the article introduced the circuit principle of deigning preamplifier and ADC circuit with I/V conversion, instrumentation amplifier, low-pass filter and 16-bit A/D transformation. At the same time the article discussed the circuit's noise suppression and isolation according to the characteristics of the weak signal, and gave the method of software rectification. Finally, tested the weak signal with keithley2000, and got a good effect.

Two overlapping two-component systems in Xanthomonas oryzae pv. oryzae contribute to full fitness in rice by regulating virulence factors expression

PubMed Central

Zheng, Dehong; Yao, Xiaoyan; Duan, Meng; Luo, Yufeng; Liu, Biao; Qi, Pengyuan; Sun, Ming; Ruan, Lifang

2016-01-01

Two-component signal transduction systems (TCSs) are widely used by bacteria to adapt to the environment. In the present study, StoS (stress tolerance-related oxygen sensor) and SreKRS (salt response kinase, regulator, and sensor) were found to positively regulate extracellular polysaccharide (EPS) production and swarming in the rice pathogen Xanthomonas oryzae pv. oryzae (Xoo). Surprisingly, the absence of stoS or sreKRS did not attenuate virulence. To better understand the intrinsic functions of StoS and SreKRS, quantitative proteomics isobaric tags for relative and absolute quantitation (iTRAQ) was employed. Consistent with stoS and sreK mutants exhibiting a similar phenotype, the signalling circuits of StoS and SreKRS overlapped. Carbohydrate metabolism proteins and chemotaxis proteins, which could be responsible for EPS and swarming regulation, respectively, were reprogrammed in stoS and sreK mutants. Moreover, StoS and SreKRS demonstrated moderate expression of the major virulence factor, hypersensitive response and pathogenicity (Hrp) proteins through the HrpG-HrpX circuit. Most importantly, Xoo equipped with StoS and SreKRS outcompetes strains without StoS or SreKRS in co-infected rice and grows outside the host. Therefore, we propose that StoS and SreKRS adopt a novel strategy involving the moderation of Hrp protein expression and the promotion of EPS and motility to adapt to the environment. PMID:26957113

The MSPICE simulation of a saturating transformer

NASA Astrophysics Data System (ADS)

Maclean, David N.

A transformer is simulated using a nonlinear saturating magnetic model. Hysteresis and gradual smooth reduction of core permeability are achieved with standard SPICE networks and functions. The equations that define the nonlinear inductance and the MSPICE circuits used to simulate them are derived. A hierarchy of circuit complexity that is based on the structured logic design subcircuit method is used. An example of a push-pull buck regulator being operated in an unbalanced condition is given. Noise ripple on the input power cable generates a dc offset current in the transformer. The example demonstrates how avionics power equipment can be evaluated for large-signal ac, dc, and transient behavior.

Hypothalamic inflammation and the central nervous system control of energy homeostasis.

PubMed

Pimentel, Gustavo D; Ganeshan, Kirthana; Carvalheira, José B C

2014-11-01

The control of energy homeostasis relies on robust neuronal circuits that regulate food intake and energy expenditure. Although the physiology of these circuits is well understood, the molecular and cellular response of this program to chronic diseases is still largely unclear. Hypothalamic inflammation has emerged as a major driver of energy homeostasis dysfunction in both obesity and anorexia. Importantly, this inflammation disrupts the action of metabolic signals promoting anabolism or supporting catabolism. In this review, we address the evidence that favors hypothalamic inflammation as a factor that resets energy homeostasis in pathological states. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

C. elegans Notch signaling regulates adult chemosensory response and larval molting quiescence

PubMed Central

Singh, Komudi; Chao, Michael Y.; Somers, Gerard A.; Komatsu, Hidetoshi; Corkins, Mark E.; Larkins-Ford, Jonah; Tucey, Tim; Dionne, Heather M.; Walsh, Melissa B.; Beaumont, Emma K.; Hart, Douglas P.; Lockery, Shawn; Hart, Anne C.

2011-01-01

Summary Background The conserved DOS motif proteins OSM-7 and OSM-11 function as co-ligands with canonical DSL ligands to activate C. elegans Notch receptors during development. We report herein that Notch ligands, co-ligands and the receptors LIN-12 and GLP-1 regulate two C. elegans behaviors: chemosensory avoidance of octanol and quiescence during molting lethargus. Results C. elegans lacking osm-7 or osm-11 are defective in their response to octanol. We find that OSM-11 is secreted from hypodermal seam cells into the pseudocoelomic body cavity and acts non-cell autonomously as a diffusible factor. OSM-11 acts with the DSL ligand LAG-2 to activate LIN-12 and GLP-1 Notch receptors in the neurons of adult animals,- thereby regulating octanol avoidance response. In adult animals, over-expression of osm-11 and consequent Notch receptor activation induces anachronistic sleep-like quiescence. Perturbation of Notch signaling altered basal activity in adults as well as arousal thresholds and quiescence during molting lethargus. Genetic epistasis studies revealed that Notch signaling regulates quiescence via previously identified circuits and genetic pathways including the egl-4 cGMP-dependent kinase. Conclusions Our findings indicate that the conserved Notch pathway modulates behavior in adult C. elegans in response to environmental stress. Additionally, Notch signaling regulates sleep-like quiescence in C. elegans suggesting Notch may regulate sleep in other species. PMID:21549604

Apparatus for controlling the firing of rectifiers in polyphase rectifying circuits

DOEpatents

Yarema, R.J.

1979-09-18

A polyphase rectifier is controlled with precision by a circuit that filters and shifts a reference signal associated with each phase and that starts a ramp signal at a zero crossing of the shifted reference signal. The difference between the ramp signal and an external trigger signal is used to generate a pulse that switches power rectifiers into conduction. The circuit reduces effects of variations that introduce subharmonics into a rectified signal and it can be used for constant or time-varying external trigger signals.

Ammonia modifies enteric neuromuscular transmission through glial γ-aminobutyric acid signaling.

PubMed

Fried, David E; Watson, Ralph E; Robson, Simon C; Gulbransen, Brian D

2017-12-01

Impaired gut motility may contribute, at least in part, to the development of systemic hyperammonemia and systemic neurological disorders in inherited metabolic disorders, or in severe liver and renal disease. It is not known whether enteric neurotransmission regulates intestinal luminal and hence systemic ammonia levels by induced changes in motility. Here, we propose and test the hypothesis that ammonia acts through specific enteric circuits to influence gut motility. We tested our hypothesis by recording the effects of ammonia on neuromuscular transmission in tissue samples from mice, pigs, and humans and investigated specific mechanisms using novel mutant mice, selective drugs, cellular imaging, and enzyme-linked immunosorbent assays. Exogenous ammonia increased neurogenic contractions and decreased neurogenic relaxations in segments of mouse, pig, and human intestine. Enteric glial cells responded to ammonia with intracellular Ca 2+ responses. Inhibition of glutamine synthetase and the deletion of glial connexin-43 channels in hGFAP :: Cre ER T2+/- /connexin43 f/f mice potentiated the effects of ammonia on neuromuscular transmission. The effects of ammonia on neuromuscular transmission were blocked by GABA A receptor antagonists, and ammonia drove substantive GABA release as did the selective pharmacological activation of enteric glia in GFAP::hM3Dq transgenic mice. We propose a novel mechanism whereby local ammonia is operational through GABAergic glial signaling to influence enteric neuromuscular circuits that regulate intestinal motility. Therapeutic manipulation of these mechanisms may benefit a number of neurological, hepatic, and renal disorders manifesting hyperammonemia. NEW & NOTEWORTHY We propose that local circuits in the enteric nervous system sense and regulate intestinal ammonia. We show that ammonia modifies enteric neuromuscular transmission to increase motility in human, pig, and mouse intestine model systems. The mechanisms underlying the effects of ammonia on enteric neurotransmission include GABAergic pathways that are regulated by enteric glial cells. Our new data suggest that myenteric glial cells sense local ammonia and directly modify neurotransmission by releasing GABA. Copyright © 2017 the American Physiological Society.

Final Technical Report

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

Michael Laub

2008-12-29

Our team of investigators from MIT (Michael Laub) and Stanford (Harley McAdams and Lucy Shapiro) conducted a multi-faceted, systematic experimental analysis of the 106 Caulobacter two-component signal transduction system proteins (62 histidine kinases and 44 response regulators) to understand how they coordinate cell cycle progression, metabolism, and response to environmental changes. These two-component signaling proteins were characterized at the genetic, biochemical, and genomic levels. The results generated by our laboratories have provided numerous insights into how Caulobacter cells sense and respond to a myriad of signals. As nearly all bacteria use two-component signaling for cell regulation, the results from thismore » project help to deepen our general understanding of bacterial signal transduction. The tools and approaches developed can be applied to other bacteria. In particular, work from the Laub laboratory now enables the systematic, rational rewiring of two-component signaling proteins, a major advance that stands to impact synthetic biology and the development of biosensors and other designer molecular circuits. Results are summarized from our work. Each section lists publications and publicly-available resources which result from the work described.« less

Optimal Signal Processing in Small Stochastic Biochemical Networks

PubMed Central

Ziv, Etay; Nemenman, Ilya; Wiggins, Chris H.

2007-01-01

We quantify the influence of the topology of a transcriptional regulatory network on its ability to process environmental signals. By posing the problem in terms of information theory, we do this without specifying the function performed by the network. Specifically, we study the maximum mutual information between the input (chemical) signal and the output (genetic) response attainable by the network in the context of an analytic model of particle number fluctuations. We perform this analysis for all biochemical circuits, including various feedback loops, that can be built out of 3 chemical species, each under the control of one regulator. We find that a generic network, constrained to low molecule numbers and reasonable response times, can transduce more information than a simple binary switch and, in fact, manages to achieve close to the optimal information transmission fidelity. These high-information solutions are robust to tenfold changes in most of the networks' biochemical parameters; moreover they are easier to achieve in networks containing cycles with an odd number of negative regulators (overall negative feedback) due to their decreased molecular noise (a result which we derive analytically). Finally, we demonstrate that a single circuit can support multiple high-information solutions. These findings suggest a potential resolution of the “cross-talk” phenomenon as well as the previously unexplained observation that transcription factors that undergo proteolysis are more likely to be auto-repressive. PMID:17957259

Direct hypothalamic and indirect trans-pallidal, trans-thalamic, or trans-septal control of accumbens signaling and their roles in food intake

PubMed Central

Urstadt, Kevin R.; Stanley, B. Glenn

2015-01-01

Due in part to the increasing incidence of obesity in developed nations, recent research aims to elucidate neural circuits that motivate humans to overeat. Earlier research has described how the nucleus accumbens shell (AcbSh) motivates organisms to feed by activating neuronal populations in the lateral hypothalamus (LH). However, more recent research suggests that the LH may in turn communicate with the AcbSh, both directly and indirectly, to re-tune the motivation to consume foods with homeostatic and food-related sensory signals. Here, we discuss the functional and anatomical evidence for an LH to AcbSh connection and its role in eating behaviors. The LH appears to modulate Acb activity directly, using neurotransmitters such as hypocretin/orexin or melanin concentrating hormone (MCH). The LH also indirectly regulates AcbSh activity through certain subcortical “relay” regions, such as the lateral septum (LS), ventral pallidum (VP), and paraventricular thalamus, using a variety of neurotransmitters. This review aims to summarize studies on these topics and outline a model by which LH circuits processing energy balance can modulate AcbSh neural activity to regulate feeding behavior. PMID:25741246

Wireless and batteryless biomedical microsystem for neural recording and epilepsy suppression based on brain focal cooling.

PubMed

Hou, K-C; Chang, C-W; Chiou, J-C; Huang, Y-H; Shaw, F-Z

2011-12-01

This work presents a biomedical microsystem with a wireless radiofrequency (RF)-powered electronics and versatile sensors/actuators for use in nanomedicinal diagnosis and therapy. The cooling of brain tissue has the potential to reduce the frequency and severity of epilepsy. Miniaturised spiral coils as a wireless power module with low-dropout linear regulator circuit convert RF signals into a DC voltage, can be implanted without a battery in monitoring free behaviour. A thermoelectric (TE) cooler is an actuator that is employed to cool down brain tissue to suppress epilepsy. Electroencephalogram (EEG) electrodes and TE coolers are integrated to form module that is placed inside the head of a rat and fastened with a bio-compatible material. EEG signals are used to identify waveforms associated with epilepsy and are measured using readout circuits. The wireless part of the presented design achieves a low quiescent current and line/load regulation and high antenna/current efficiency with thermal protection to avoid damage to the implanted tissue. Epilepsy is suppressed by reducing the temperature to reduce the duration of this epileptic episode. Related characterisations demonstrate that the proposed design can be adopted in an effective nanomedicine microsystem.

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

Nishimura, Takahiro, E-mail: t-nishimura@ist.osaka-u.ac.jp; Fujii, Ryo; Ogura, Yusuke

Molecular logic circuits represent a promising technology for observation and manipulation of biological systems at the molecular level. However, the implementation of molecular logic circuits for temporal and programmable operation remains challenging. In this paper, we demonstrate an optically controllable logic circuit that uses fluorescence resonance energy transfer (FRET) for signaling. The FRET-based signaling process is modulated by both molecular and optical inputs. Based on the distance dependence of FRET, the FRET pathways required to execute molecular logic operations are formed on a DNA nanostructure as a circuit based on its molecular inputs. In addition, the FRET pathways on themore » DNA nanostructure are controlled optically, using photoswitching fluorescent molecules to instruct the execution of the desired operation and the related timings. The behavior of the circuit can thus be controlled using external optical signals. As an example, a molecular logic circuit capable of executing two different logic operations was studied. The circuit contains functional DNAs and a DNA scaffold to construct two FRET routes for executing Input 1 AND Input 2 and Input 1 AND NOT Input 3 operations on molecular inputs. The circuit produced the correct outputs with all possible combinations of the inputs by following the light signals. Moreover, the operation execution timings were controlled based on light irradiation and the circuit responded to time-dependent inputs. The experimental results demonstrate that the circuit changes the output for the required operations following the input of temporal light signals.« less

Automated Design Tools for Integrated Mixed-Signal Microsystems (NeoCAD)

DTIC Science & Technology

2005-02-01

method, Model Order Reduction (MOR) tools, system-level, mixed-signal circuit synthesis and optimization tools, and parsitic extraction tools. A unique...Mission Area: Command and Control mixed signal circuit simulation parasitic extraction time-domain simulation IC design flow model order reduction... Extraction 1.2 Overall Program Milestones CHAPTER 2 FAST TIME DOMAIN MIXED-SIGNAL CIRCUIT SIMULATION 2.1 HAARSPICE Algorithms 2.1.1 Mathematical Background

Dissecting Immune Circuits by Linking CRISPR-Pooled Screens with Single-Cell RNA-Seq.

PubMed

Jaitin, Diego Adhemar; Weiner, Assaf; Yofe, Ido; Lara-Astiaso, David; Keren-Shaul, Hadas; David, Eyal; Salame, Tomer Meir; Tanay, Amos; van Oudenaarden, Alexander; Amit, Ido

2016-12-15

In multicellular organisms, dedicated regulatory circuits control cell type diversity and responses. The crosstalk and redundancies within these circuits and substantial cellular heterogeneity pose a major research challenge. Here, we present CRISP-seq, an integrated method for massively parallel single-cell RNA sequencing (RNA-seq) and clustered regularly interspaced short palindromic repeats (CRISPR)-pooled screens. We show that profiling the genomic perturbation and transcriptome in the same cell enables us to simultaneously elucidate the function of multiple factors and their interactions. We applied CRISP-seq to probe regulatory circuits of innate immunity. By sampling tens of thousands of perturbed cells in vitro and in mice, we identified interactions and redundancies between developmental and signaling-dependent factors. These include opposing effects of Cebpb and Irf8 in regulating the monocyte/macrophage versus dendritic cell lineages and differential functions for Rela and Stat1/2 in monocyte versus dendritic cell responses to pathogens. This study establishes CRISP-seq as a broadly applicable, comprehensive, and unbiased approach for elucidating mammalian regulatory circuits. Copyright © 2016 Elsevier Inc. All rights reserved.

The human phosphotyrosine signaling network: Evolution and hotspots of hijacking in cancer

PubMed Central

Li, Lei; Tibiche, Chabane; Fu, Cong; Kaneko, Tomonori; Moran, Michael F.; Schiller, Martin R.; Li, Shawn Shun-Cheng; Wang, Edwin

2012-01-01

Phosphotyrosine (pTyr) signaling, which plays a central role in cell–cell and cell–environment interactions, has been considered to be an evolutionary innovation in multicellular metazoans. However, neither the emergence nor the evolution of the human pTyr signaling system is currently understood. Tyrosine kinase (TK) circuits, each of which consists of a TK writer, a kinase substrate, and a related reader, such as Src homology (SH) 2 domains and pTyr-binding (PTB) domains, comprise the core machinery of the pTyr signaling network. In this study, we analyzed the evolutionary trajectories of 583 literature-derived and 50,000 computationally predicted human TK circuits in 19 representative eukaryotic species and assigned their evolutionary origins. We found that human TK circuits for intracellular pTyr signaling originated largely from primitive organisms, whereas the inter- or extracellular signaling circuits experienced significant expansion in the bilaterian lineage through the “back-wiring” of newly evolved kinases to primitive substrates and SH2/PTB domains. Conversely, the TK circuits that are involved in tissue-specific signaling evolved mainly in vertebrates by the back-wiring of vertebrate substrates to primitive kinases and SH2/PTB domains. Importantly, we found that cancer signaling preferentially employs the pTyr sites, which are linked to more TK circuits. Our work provides insights into the evolutionary paths of the human pTyr signaling circuits and suggests the use of a network approach for cancer intervention through the targeting of key pTyr sites and their associated signaling hubs in the network. PMID:22194470

Apparatus and method for detecting and measuring changes in linear relationships between a number of high frequency signals

DOEpatents

Bittner, J.W.; Biscardi, R.W.

1991-03-19

An electronic measurement circuit is disclosed for high speed comparison of the relative amplitudes of a predetermined number of electrical input signals independent of variations in the magnitude of the sum of the signals. The circuit includes a high speed electronic switch that is operably connected to receive on its respective input terminals one of said electrical input signals and to have its common terminal serve as an input for a variable-gain amplifier-detector circuit that is operably connected to feed its output to a common terminal of a second high speed electronic switch. The respective terminals of the second high speed electronic switch are operably connected to a plurality of integrating sample and hold circuits, which in turn have their outputs connected to a summing logic circuit that is operable to develop first, second and third output voltages, the first output voltage being proportional to a predetermined ratio of sums and differences between the compared input signals, the second output voltage being proportional to a second summed ratio of predetermined sums and differences between said input signals, and the third output voltage being proportional to the sum of signals to the summing logic circuit. A servo system that is operably connected to receive said third output signal and compare it with a reference voltage to develop a slowly varying feedback voltage to control the variable-gain amplifier in said common amplifier-detector circuit in order to make said first and second output signals independent of variations in the magnitude of the sum of said input signals. 2 figures.

Apparatus and method for detecting and measuring changes in linear relationships between a number of high frequency signals

DOEpatents

Bittner, John W.; Biscardi, Richard W.

1991-01-01

An electronic measurement circuit for high speed comparison of the relative amplitudes of a predetermined number of electrical input signals independent of variations in the magnitude of the sum of the signals. The circuit includes a high speed electronic switch that is operably connected to receive on its respective input terminals one of said electrical input signals and to have its common terminal serve as an input for a variable-gain amplifier-detector circuit that is operably connected to feed its output to a common terminal of a second high speed electronic switch. The respective terminals of the second high speed electronic switch are operably connected to a plurality of integrating sample and hold circuits, which in turn have their outputs connected to a summing logic circuit that is operable to develop first, second and third output voltages, the first output voltage being proportional to a predetermined ratio of sums and differences between the compared input signals, the second output voltage being proportional to a second summed ratio of predetermined sums and differences between said input signals, and the third output voltage being proportional to the sum of signals to the summing logic circuit. A servo system that is operably connected to receive said third output signal and compare it with a reference voltage to develop a slowly varying feedback voltage to control the variable-gain amplifier in said common amplifier-detector circuit in order to make said first and second output signals independent of variations in the magnitude of the sum of said input signals.

A feedback circuit between miR-133 and the ERK1/2 pathway involving an exquisite mechanism for regulating myoblast proliferation and differentiation

PubMed Central

Feng, Y; Niu, L-L; Wei, W; Zhang, W-Y; Li, X-Y; Cao, J-H; Zhao, S-H

2013-01-01

MiR-133 was found to be specifically expressed in cardiac and skeletal muscle in previous studies. There are two members in the miR-133 family: miR-133a and miR-133b. Although previous studies indicated that miR-133a was related to myogenesis, the signaling pathways regulated by miR-133 were still not very clear. In this study, we showed that both miR-133a and miR-133b were upregulated during myogenesis through Solexa sequencing. We confirmed that miR-133 could promote myoblast differentiation and inhibit cell proliferation through the regulation of the extracellular signal-regulated kinase (ERK) signaling pathway in C2C12 cells. FGFR1 and PP2AC, which both participate in signal transduction of the ERK1/2 pathway, were found to be negatively regulated by miR-133a and miR-133b at the post-transcriptional level. Also, downregulation of ERK1/2 phosphorylation by miR-133 was detected. FGFR1 and PP2AC were also found to repress C2C12 differentiation by specific siRNAs. In addition, we found that inhibition of ERK1/2 pathway activity can inhibit C2C12 cell proliferation and promote the initiation of differentiation but form short and small myotubes. Furthermore, we found that the expression of miR-133 was negatively regulated by ERK1/2 signaling pathway. In summary, we demonstrated the role of miR-133 in myoblast and further revealed a new feedback loop between miR-133 and the ERK1/2 signaling pathway involving an exquisite mechanism for regulating myogenesis. PMID:24287695

A feedback circuit between miR-133 and the ERK1/2 pathway involving an exquisite mechanism for regulating myoblast proliferation and differentiation.

PubMed

Feng, Y; Niu, L-L; Wei, W; Zhang, W-Y; Li, X-Y; Cao, J-H; Zhao, S-H

2013-11-28

MiR-133 was found to be specifically expressed in cardiac and skeletal muscle in previous studies. There are two members in the miR-133 family: miR-133a and miR-133b. Although previous studies indicated that miR-133a was related to myogenesis, the signaling pathways regulated by miR-133 were still not very clear. In this study, we showed that both miR-133a and miR-133b were upregulated during myogenesis through Solexa sequencing. We confirmed that miR-133 could promote myoblast differentiation and inhibit cell proliferation through the regulation of the extracellular signal-regulated kinase (ERK) signaling pathway in C2C12 cells. FGFR1 and PP2AC, which both participate in signal transduction of the ERK1/2 pathway, were found to be negatively regulated by miR-133a and miR-133b at the post-transcriptional level. Also, downregulation of ERK1/2 phosphorylation by miR-133 was detected. FGFR1 and PP2AC were also found to repress C2C12 differentiation by specific siRNAs. In addition, we found that inhibition of ERK1/2 pathway activity can inhibit C2C12 cell proliferation and promote the initiation of differentiation but form short and small myotubes. Furthermore, we found that the expression of miR-133 was negatively regulated by ERK1/2 signaling pathway. In summary, we demonstrated the role of miR-133 in myoblast and further revealed a new feedback loop between miR-133 and the ERK1/2 signaling pathway involving an exquisite mechanism for regulating myogenesis.

Noise isolation system for high-speed circuits

DOEpatents

McNeilly, D.R.

1983-12-29

A noise isolation circuit is provided that consists of a dual function bypass which confines high-speed switching noise to the component or circuit which generates it and isolates the component or circuit from high-frequency noise transients which may be present on the ground and power supply busses. A local circuit ground is provided which is coupled to the system ground by sufficient impedance to force the dissipation of the noise signal in the local circuit or component generating the noise. The dual function bypass network couples high-frequency noise signals generated in the local component or circuit through a capacitor to the local ground while isolating the component or circuit from noise signals which may be present on the power supply busses or system ground. The network is an effective noise isolating system and is applicable to both high-speed analog and digital circuits.

Noise isolation system for high-speed circuits

DOEpatents

McNeilly, David R.

1986-01-01

A noise isolation circuit is provided that consists of a dual function bypass which confines high-speed switching noise to the component or circuit which generates it and isolates the component or circuit from high-frequency noise transients which may be present on the ground and power supply busses. A local circuit ground is provided which is coupled to the system ground by sufficient impedance to force the dissipation of the noise signal in the local circuit or component generating the noise. The dual function bypass network couples high-frequency noise signals generated in the local component or circuit through a capacitor to the local ground while isolating the component or circuit from noise signals which may be present on the power supply busses or system ground. The network is an effective noise isolating system and is applicable to both high-speed analog and digital circuits.

Practical Active Capacitor Filter

NASA Technical Reports Server (NTRS)

Shuler, Robert L., Jr. (Inventor)

2005-01-01

A method and apparatus is described that filters an electrical signal. The filtering uses a capacitor multiplier circuit where the capacitor multiplier circuit uses at least one amplifier circuit and at least one capacitor. A filtered electrical signal results from a direct connection from an output of the at least one amplifier circuit.

Design and performance of heart assist or artificial heart control systems

NASA Technical Reports Server (NTRS)

Webb, J. A., Jr.; Gebben, V. D.

1978-01-01

The factors leading to the design of a controlled driving system for either a heart assist pump or artificial heart are discussed. The system provides square pressure waveform to drive a pneumatic-type blood pump. For assist usage the system uses an R-wave detector circuit that can detect the R-wave of the electrocardiogram in the presence of electrical disturbances. This circuit provides a signal useful for synchronizing an assist pump with the natural heart. It synchronizes a square wave circuit, the output of which is converted into square waveforms of pneumatic pressure suitable for driving both assist device and artificial heart. The pressure levels of the driving waveforms are controlled by means of feedback channels to maintain physiological regulation of the artificial heart's output flow. A more compact system that could achieve similar regulatory characteristics is also discussed.

RF lockout circuit for electronic locking system

NASA Astrophysics Data System (ADS)

Becker, Earl M., Jr.; Miller, Allen

1991-02-01

An electronics lockout circuit was invented that includes an antenna adapted to receive radio frequency signals from a transmitter, and a radio frequency detector circuit which converts the radio frequency signals into a first direct current voltage indicative of the relative strength of the field resulting from the radio frequency signals. The first direct current voltage is supplied to a trigger circuit which compares this direct current voltage to an adjustable direct current reference voltage. This provides a second direct current voltage at the output whenever the amplitude of the first direct current voltage exceeds the amplitude of the reference voltage provided by the comparator circuit. This is supplied to a disconnect relay circuit which, upon receiving a signal from the electronic control unit of an electronic combination lock during the time period at which the second direct current voltage is present, isolates the door strike coil of a security door from the electronic control unit. This prevents signals falsely generated by the electronic control unit because of radio frequency signals in the vicinity of the electronic control unit energizing the door strike coil and accidentally opening a security door.

Aldosterone-Sensing Neurons in the NTS Exhibit State-Dependent Pacemaker Activity and Drive Sodium Appetite via Synergy with Angiotensin II Signaling.

PubMed

Resch, Jon M; Fenselau, Henning; Madara, Joseph C; Wu, Chen; Campbell, John N; Lyubetskaya, Anna; Dawes, Brian A; Tsai, Linus T; Li, Monica M; Livneh, Yoav; Ke, Qingen; Kang, Peter M; Fejes-Tóth, Géza; Náray-Fejes-Tóth, Anikó; Geerling, Joel C; Lowell, Bradford B

2017-09-27

Sodium deficiency increases angiotensin II (ATII) and aldosterone, which synergistically stimulate sodium retention and consumption. Recently, ATII-responsive neurons in the subfornical organ (SFO) and aldosterone-sensitive neurons in the nucleus of the solitary tract (NTS HSD2 neurons) were shown to drive sodium appetite. Here we investigate the basis for NTS HSD2 neuron activation, identify the circuit by which NTS HSD2 neurons drive appetite, and uncover an interaction between the NTS HSD2 circuit and ATII signaling. NTS HSD2 neurons respond to sodium deficiency with spontaneous pacemaker-like activity-the consequence of "cardiac" HCN and Na v 1.5 channels. Remarkably, NTS HSD2 neurons are necessary for sodium appetite, and with concurrent ATII signaling their activity is sufficient to produce rapid consumption. Importantly, NTS HSD2 neurons stimulate appetite via projections to the vlBNST, which is also the effector site for ATII-responsive SFO neurons. The interaction between angiotensin signaling and NTS HSD2 neurons provides a neuronal context for the long-standing "synergy hypothesis" of sodium appetite regulation. Copyright © 2017 Elsevier Inc. All rights reserved.

Self-regulating proportionally controlled heating apparatus and technique

NASA Technical Reports Server (NTRS)

Strange, M. G. (Inventor)

1975-01-01

A self-regulating proportionally controlled heating apparatus and technique is provided wherein a single electrical resistance heating element having a temperature coefficient of resistance serves simultaneously as a heater and temperature sensor. The heating element is current-driven and the voltage drop across the heating element is monitored and a component extracted which is attributable to a change in actual temperature of the heating element from a desired reference temperature, so as to produce a resulting error signal. The error signal is utilized to control the level of the heater drive current and the actual heater temperature in a direction to reduce the noted temperature difference. The continuous nature of the process for deriving the error signal feedback information results in true proportional control of the heating element without the necessity for current-switching which may interfere with nearby sensitive circuits, and with no cyclical variation in the controlled temperature.

Deconstructing transcriptional heterogeneity in pluripotent stem cells

PubMed Central

Shalek, Alex K.; Satija, Rahul; DaleyKeyser, AJay; Li, Hu; Zhang, Jin; Pardee, Keith; Gennert, David; Trombetta, John J.; Ferrante, Thomas C.; Regev, Aviv; Daley, George Q.; Collins, James J.

2014-01-01

SUMMARY Pluripotent stem cells (PSCs) are capable of dynamic interconversion between distinct substates, but the regulatory circuits specifying these states and enabling transitions between them are not well understood. We set out to characterize transcriptional heterogeneity in PSCs by single-cell expression profiling under different chemical and genetic perturbations. Signaling factors and developmental regulators show highly variable expression, with expression states for some variable genes heritable through multiple cell divisions. Expression variability and population heterogeneity can be influenced by perturbation of signaling pathways and chromatin regulators. Strikingly, either removal of mature miRNAs or pharmacologic blockage of signaling pathways drives PSCs into a low-noise ground state characterized by a reconfigured pluripotency network, enhanced self-renewal, and a distinct chromatin state, an effect mediated by opposing miRNA families acting on the c-myc / Lin28 / let-7 axis. These data illuminate the nature of transcriptional heterogeneity in PSCs. PMID:25471879

Morphological Analysis of the Axonal Projections of EGFP-Labeled Esr1-Expressing Neurons in Transgenic Female Medaka.

PubMed

Zempo, Buntaro; Karigo, Tomomi; Kanda, Shinji; Akazome, Yasuhisa; Oka, Yoshitaka

2018-02-01

Some hypothalamic neurons expressing estrogen receptor α (Esr1) are thought to transmit a gonadal estrogen feedback signal to gonadotropin-releasing hormone 1 (GnRH1) neurons, which is the final common pathway for feedback regulation of reproductive functions. Moreover, estrogen-sensitive neurons are suggested to control sexual behaviors in coordination with reproduction. In mammals, hypothalamic estrogen-sensitive neurons release the peptide kisspeptin and regulate GnRH1 neurons. However, a growing body of evidence in nonmammalian species casts doubt on the regulation of GnRH1 neurons by kisspeptin neurons. As a step toward understanding how estrogen regulates neuronal circuits for reproduction and sex behavior in vertebrates in general, we generated a transgenic (Tg) medaka that expresses enhanced green fluorescent protein (EGFP) specifically in esr1-expressing neurons (esr1 neurons) and analyzed their axonal projections. We found that esr1 neurons in the preoptic area (POA) project to the gnrh1 neurons. We also demonstrated by transcriptome and histological analyses that these esr1 neurons are glutamatergic or γ-aminobutyric acidergic (GABAergic) but not kisspeptinergic. We therefore suggest that glutamatergic and GABAergic esr1 neurons in the POA regulate gnrh1 neurons. This hypothesis is consistent with previous studies in mice that found that glutamatergic and GABAergic transmission is critical for estrogen-dependent changes in GnRH1 neuron firing. Thus, we propose that this neuronal circuit may provide an evolutionarily conserved mechanism for regulation of reproduction. In addition, we showed that telencephalic esr1 neurons project to medulla, which may control sexual behavior. Moreover, we found that some POA-esr1 neurons coexpress progesterone receptors. These neurons may form the neuronal circuits that regulate reproduction and sex behavior in response to the serum estrogen/progesterone. Copyright © 2018 Endocrine Society.

An electronic circuit that detects left ventricular ejection events by processing the arterial pressure waveform

NASA Technical Reports Server (NTRS)

Gebben, V. D.; Webb, J. A., Jr.

1972-01-01

An electronic circuit for processing arterial blood pressure waveform signals is described. The circuit detects blood pressure as the heart pumps blood through the aortic valve and the pressure distribution caused by aortic valve closure. From these measurements, timing signals for use in measuring the left ventricular ejection time is determined, and signals are provided for computer monitoring of the cardiovascular system. Illustrations are given of the circuit and pressure waveforms.

Low-noise pulse conditioner

DOEpatents

Bird, D.A.

1981-06-16

A low-noise pulse conditioner is provided for driving electronic digital processing circuitry directly from differentially induced input pulses. The circuit uses a unique differential-to-peak detector circuit to generate a dynamic reference signal proportional to the input peak voltage. The input pulses are compared with the reference signal in an input network which operates in full differential mode with only a passive input filter. This reduces the introduction of circuit-induced noise, or jitter, generated in ground referenced input elements normally used in pulse conditioning circuits, especially speed transducer processing circuits. This circuit may be used for conditioning the sensor signal from the Fidler coil in a gas centrifuge for separation of isotopic gaseous mixtures.

Circuit Methods for VLF Antenna Couplers. [for use in Loran or Omega receiver systems

NASA Technical Reports Server (NTRS)

Burhans, R. W.

1977-01-01

The limitations of different E-field antenna coupler or preamplifier circuits are presented. All circuits were evaluated using actual Loran or Omega signals. Electric field whip or wire antennas are the simplest types which can be used for reception of VLF signals in the 10 to 100 kHz range. JFET or MOSFET transistors provide impedance transformation and some voltage gain in simple circuits where the power for operating the preamplifier uses the same coaxial cable that feeds the signal back to the receiver. The circuit techniques provide useful alternative methods for Loran-Omega receiver system designers.

Low power electromagnetic flowmeter providing accurate zero set

NASA Technical Reports Server (NTRS)

Fryer, T. B. (Inventor)

1971-01-01

A low power, small size electromagnetic flowmeter system is described which produces a zero output signal for zero flow. The system comprises an air core type electromagnetic flow transducer, a field current supply circuit for the transducer coils and a pre-amplifier and demodulation circuit connected to the output of the transducer. To prevent spurious signals at zero flow, separate, isolated power supplies are provided for the two circuits. The demodulator includes a pair of synchronous rectifiers which are controlled by signals from the field current supply circuit. Pulse transformer connected in front of the synchronous rectifiers provide isolation between the two circuits.

Design and Application of a Circuit for Measuring Frequency and Duty Cycle of Stimulated Bioelectrical Signal

NASA Astrophysics Data System (ADS)

Tang, Li-Ming; Chang, Ben-Kang; Liu, Tie-Bing; Wu, Min; Ling, Gang

2002-12-01

To design a new type of circuit for measuring frequency & duty cycle of stimulated bioelectrical signal for the project of 'the map of neuron-threshold in human brain and its clinical application'. This circuit was designed according to the character of stimulated bioelectrical signals. It was tested and improved and then used in the neuron -threshold stimulator. The circuit was found to be very accurate for measuring frequency and the error for measuring duty cycle was below 0.2%. This circuit is well-designed, simple, easy to use, and can be applied in many systems.

TOFPET2: a high-performance ASIC for time and amplitude measurements of SiPM signals in time-of-flight applications

NASA Astrophysics Data System (ADS)

Di Francesco, A.; Bugalho, R.; Oliveira, L.; Pacher, L.; Rivetti, A.; Rolo, M.; Silva, J. C.; Silva, R.; Varela, J.

2016-03-01

We present a readout and digitization ASIC featuring low-noise and low-power for time-of flight (TOF) applications using SiPMs. The circuit is designed in standard CMOS 110 nm technology, has 64 independent channels and is optimized for time-of-flight measurement in Positron Emission Tomography (TOF-PET). The input amplifier is a low impedance current conveyor based on a regulated common-gate topology. Each channel has quad-buffered analogue interpolation TDCs (time binning 20 ps) and charge integration ADCs with linear response at full scale (1500 pC). The signal amplitude can also be derived from the measurement of time-over-threshold (ToT). Simulation results show that for a single photo-electron signal with charge 200 (550) fC generated by a SiPM with 320 pF capacitance the circuit has 24 (30) dB SNR, 75(39) ps r.m.s. resolution, and 4(8) mW power consumption. The event rate is 600 kHz per channel, with up to 2 MHz dark counts rejection.

The technology on noise reduction of the APD detection circuit

NASA Astrophysics Data System (ADS)

Wu, Xue-ying; Zheng, Yong-chao; Cui, Jian-yong

2013-09-01

The laser pulse detection is widely used in the field of laser range finders, laser communications, laser radar, laser Identification Friend or Foe, et al, for the laser pulse detection has the advantage of high accuracy, high sensitivity and strong anti-interference. The avalanche photodiodes (APD) has the advantage of high quantum efficiency, high response speed and huge gain. The APD is particularly suitable for weak signal detection. The technology that APD acts as the photodetector for weak signal reception and amplification is widely used in laser pulse detection. The APD will convert the laser signal to weak electrical signal. The weak signal is amplified, processed and exported by the circuit. In the circuit design, the optimal signal detection is one key point in photoelectric detection system. The issue discusses how to reduce the noise of the photoelectric signal detection circuit and how to improve the signal-to-noise ratio, related analysis and practice included. The essay analyzes the mathematical model of the signal-to-noise ratio for photoelectric conversion and the noise of the APD photoelectric detection system. By analysis the bandwidth of the detection system is determined, and the circuit devices are selected that match the APD. In the circuit design separated devices with low noise are combined with integrated operational amplifier for the purpose of noise reduction. The methods can effectively suppress the noise, and improve the detection sensitivity.

Stability of the Baseline Holder in Readout Circuits For Radiation Detectors

PubMed Central

Chen, Y.; Cui, Y.; O’Connor, P.; Seo, Y.; Camarda, G. S.; Hossain, A.; Roy, U.; Yang, G.; James, R. B.

2016-01-01

Baseline holder (BLH) circuits are used widely to stabilize the analog output of application-specific integrated circuits (ASICs) for high-count-rate applications. The careful design of BLH circuits is vital to the overall stability of the analog-signal-processing chain in ASICs. Recently, we observed self-triggered fluctuations in an ASIC in which the shaping circuits have a BLH circuit in the feedback loop. In fact, further investigations showed that methods of enhancing small-signal stabilities cause an even worse situation. To resolve this problem, we used large-signal analyses to study the circuit’s stability. We found that a relatively small gain for the error amplifier and a small current in the non-linear stage of the BLH are required to enhance stability in large-signal analysis, which will compromise the properties of the BLH. These findings were verified by SPICE simulations. In this paper, we present our detailed analysis of the BLH circuits, and propose an improved version of them that have only minimal self-triggered fluctuations. We summarize the design considerations both for the stability and the properties of the BLH circuits. PMID:27182081

Realization of rapid debugging for detection circuit of optical fiber gas sensor: Using an analog signal source

NASA Astrophysics Data System (ADS)

Tian, Changbin; Chang, Jun; Wang, Qiang; Wei, Wei; Zhu, Cunguang

2015-03-01

An optical fiber gas sensor mainly consists of two parts: optical part and detection circuit. In the debugging for the detection circuit, the optical part usually serves as a signal source. However, in the debugging condition, the optical part can be easily influenced by many factors, such as the fluctuation of ambient temperature or driving current resulting in instability of the wavelength and intensity for the laser; for dual-beam sensor, the different bends and stresses of the optical fiber will lead to the fluctuation of the intensity and phase; the intensity noise from the collimator, coupler, and other optical devices in the system will also result in the impurity of the optical part based signal source. In order to dramatically improve the debugging efficiency of the detection circuit and shorten the period of research and development, this paper describes an analog signal source, consisting of a single chip microcomputer (SCM), an amplifier circuit, and a voltage-to-current conversion circuit. It can be used to realize the rapid debugging detection circuit of the optical fiber gas sensor instead of optical part based signal source. This analog signal source performs well with many other advantages, such as the simple operation, small size, and light weight.

Prototype Parts of a Digital Beam-Forming Wide-Band Receiver

NASA Technical Reports Server (NTRS)

Kaplan, Steven B.; Pylov, Sergey V.; Pambianchi, Michael

2003-01-01

Some prototype parts of a digital beamforming (DBF) receiver that would operate at multigigahertz carrier frequencies have been developed. The beam-forming algorithm in a DBF receiver processes signals from multiple antenna elements with appropriate time delays and weighting factors chosen to enhance the reception of signals from a specific direction while suppressing signals from other directions. Such a receiver would be used in the directional reception of weak wideband signals -- for example, spread-spectrum signals from a low-power transmitter on an Earth-orbiting spacecraft or other distant source. The prototype parts include superconducting components on integrated-circuit chips, and a multichip module (MCM), within which the chips are to be packaged and connected via special inter-chip-communication circuits. The design and the underlying principle of operation are based on the use of the rapid single-flux quantum (RSFQ) family of logic circuits to obtain the required processing speed and signal-to-noise ratio. RSFQ circuits are superconducting circuits that exploit the Josephson effect. They are well suited for this application, having been proven to perform well in some circuits at frequencies above 100 GHz. In order to maintain the superconductivity needed for proper functioning of the RSFQ circuits, the MCM must be kept in a cryogenic environment during operation.

Structure, production and signaling of leptin

PubMed Central

Münzberg, Heike; Morrison, Christopher D.

2014-01-01

The cloning of leptin in 1994 was an important milestone in obesity research. In those days obesity was stigmatized as a condition caused by lack of character and self-control. Mutations in either leptin or its receptor were the first single gene mutations found to cause morbid obesity, and it is now appreciated that obesity is caused by a dysregulation of central neuronal circuits. From the first discovery of the leptin deficient obese mouse (ob/ob), to the cloning of leptin (ob aka lep) and leptin receptor (db aka lepr) genes, much has been learned about leptin and its action in the central nervous system. The initial high hopes that leptin would cure obesity were quickly dampened by the discovery that most obese humans have increased leptin levels and develop leptin resistance. Nevertheless, leptin target sites in the brain represent an excellent blueprint for distinct neuronal circuits that control energy homeostasis. A better understanding of the regulation and interconnection of these circuits will further guide and improve the development of safe and effective interventions to treat obesity. This review will highlight our current knowledge about the hormone leptin, its signaling pathways and its central actions to mediate distinct physiological functions. PMID:25305050

Gate drive latching circuit for an auxiliary resonant commutation circuit

NASA Technical Reports Server (NTRS)

Delgado, Eladio Clemente (Inventor); Kheraluwala, Mustansir Hussainy (Inventor)

1999-01-01

A gate drive latching circuit for an auxiliary resonant commutation circuit for a power switching inverter includes a current monitor circuit providing a current signal to a pair of analog comparators to implement latching of one of a pair of auxiliary switching devices which are used to provide commutation current for commutating switching inverters in the circuit. Each of the pair of comparators feeds a latching circuit which responds to an active one of the comparators for latching the associated gate drive circuit for one of the pair of auxiliary commutating switches. An initial firing signal is applied to each of the commutating switches to gate each into conduction and the resulting current is monitored to determine current direction and therefore the one of the switches which is carrying current. The comparator provides a latching signal to the one of the auxiliary power switches which is actually conducting current and latches that particular power switch into an on state for the duration of current through the device. The latching circuit is so designed that the only time one of the auxiliary switching devices can be latched on is during the duration of an initial firing command signal.

The Lateral Habenula Circuitry: Reward Processing and Cognitive Control

PubMed Central

Baker, Phillip M.; Jhou, Thomas; Matsumoto, Masayuki; Mizumori, Sheri J.Y.; Stephenson-Jones, Marcus

2016-01-01

There has been a growing interest in understanding the role of the lateral habenula (LHb) in reward processing, affect regulation, and goal-directed behaviors. The LHb gets major inputs from the habenula-projecting globus pallidus and the mPFC, sending its efferents to the dopaminergic VTA and SNc, serotonergic dorsal raphe nuclei, and the GABAergic rostromedial tegmental nucleus. Recent studies have made advances in our understanding of the LHb circuit organization, yet the precise mechanisms of its involvement in complex behaviors are largely unknown. To begin to address this unresolved question, we present here emerging cross-species perspectives with a goal to provide a more refined understanding of the role of the LHb circuits in reward and cognition. We begin by highlighting recent findings from rodent experiments using optogenetics, electrophysiology, molecular, pharmacology, and tracing techniques that reveal diverse neural phenotypes in the LHb circuits that may underlie previously undescribed behavioral functions. We then discuss results from electrophysiological studies in macaques that suggest that the LHb cooperates with the anterior cingulate cortex to monitor action outcomes and signal behavioral adjustment. Finally, we provide an integrated summary of cross-species findings and discuss how further research on the connectivity, neural signaling, and physiology of the LHb circuits can deepen our understanding of the role of the LHb in normal and maladaptive behaviors associated with mental illnesses and drug abuse. PMID:27911751

Central Nervous System Neuropeptide Y Signaling Modulates VLDL Triglyceride Secretion

PubMed Central

Stafford, John M.; Yu, Fang; Printz, Richard; Hasty, Alyssa H.; Swift, Larry L.; Niswender, Kevin D.

2014-01-01

OBJECTIVE Elevated triglyceride (TG) is the major plasma lipid abnormality in obese and diabetic patients and contributes to cardiovascular morbidity in these disorders. We sought to identify novel mechanisms leading to hypertriglyceridemia. Resistance to negative feedback signals from adipose tissue in key central nervous system (CNS) energy homeostatic circuits contributes to the development of obesity. Because triglycerides both represent the largest energy depot in the body and are elevated in both the plasma and adipose in obesity and diabetes, we hypothesized that the same neural circuits that regulate energy balance also regulate the secretion of TGs into plasma. RESEARCH DESIGN AND METHODS In normal fasting rats, the TG secretion rate was estimated by serial blood sampling after intravascular tyloxapol pretreatment. Neuropeptide Y (NPY) signaling in the CNS was modulated by intracerebroventricular injection of NPY, receptor antagonist, and receptor agonist. RESULTS A single intracerebroventricular injection of NPY increased TG secretion by 2.5-fold in the absence of food intake, and this was determined to be VLDL by fast performance liquid chromatography (FPLC). This effect was recapitulated by activating NPY signaling in downstream neurons with an NPY-Y5 receptor agonist. An NPY-Y1 receptor antagonist decreased the elevated TGs in the form of VLDL secretion rate by 50% compared with vehicle. Increased TG secretion was due to increased secretion of VLDL particles, rather than secretion of larger particles, because apolipoprotein B100 was elevated in FPLC fractions corresponding to VLDL. CONCLUSIONS We find that a key neuropeptide system involved in energy homeostasis in the CNS exerts control over VLDL-TG secretion into the bloodstream. PMID:18332095

Post regulation circuit with energy storage

DOEpatents

Ball, Don G.; Birx, Daniel L.; Cook, Edward G.

1992-01-01

A charge regulation circuit provides regulation of an unregulated voltage supply and provides energy storage. The charge regulation circuit according to the present invention provides energy storage without unnecessary dissipation of energy through a resistor as in prior art approaches.

Multi-format all-optical processing based on a large-scale, hybridly integrated photonic circuit.

PubMed

Bougioukos, M; Kouloumentas, Ch; Spyropoulou, M; Giannoulis, G; Kalavrouziotis, D; Maziotis, A; Bakopoulos, P; Harmon, R; Rogers, D; Harrison, J; Poustie, A; Maxwell, G; Avramopoulos, H

2011-06-06

We investigate through numerical studies and experiments the performance of a large scale, silica-on-silicon photonic integrated circuit for multi-format regeneration and wavelength-conversion. The circuit encompasses a monolithically integrated array of four SOAs inside two parallel Mach-Zehnder structures, four delay interferometers and a large number of silica waveguides and couplers. Exploiting phase-incoherent techniques, the circuit is capable of processing OOK signals at variable bit rates, DPSK signals at 22 or 44 Gb/s and DQPSK signals at 44 Gbaud. Simulation studies reveal the wavelength-conversion potential of the circuit with enhanced regenerative capabilities for OOK and DPSK modulation formats and acceptable quality degradation for DQPSK format. Regeneration of 22 Gb/s OOK signals with amplified spontaneous emission (ASE) noise and DPSK data signals degraded with amplitude, phase and ASE noise is experimentally validated demonstrating a power penalty improvement up to 1.5 dB.

DOP-2 D2-Like Receptor Regulates UNC-7 Innexins to Attenuate Recurrent Sensory Motor Neurons during C. elegans Copulation

PubMed Central

Correa, Paola A.; Gruninger, Todd

2015-01-01

Neuromodulation of self-amplifying circuits directs context-dependent behavioral executions. Although recurrent networks are found throughout the Caenorhabditis elegans connectome, few reports describe the mechanisms that regulate reciprocal neural activity during complex behavior. We used C. elegans male copulation to dissect how a goal-oriented motor behavior is regulated by recurrently wired sensory-motor neurons. As the male tail presses against the hermaphrodite's vulva, cholinergic and glutamatergic reciprocal innervations of post cloaca sensilla (PCS) neurons (PCA, PCB, and PCC), hook neurons (HOA, HOB), and their postsynaptic sex muscles execute rhythmic copulatory spicule thrusts. These repetitive spicule movements continue until the male shifts off the vulva or genital penetration is accomplished. However, the signaling mechanism that temporally and spatially restricts repetitive intromission attempts to vulva cues was unclear. Here, we report that confinement of spicule insertion attempts to the vulva is facilitated by D2-like receptor modulation of gap-junctions between PCB and the hook sensillum. We isolated a missense mutation in the UNC-7(L) gap-junction isoform, which perturbs DOP-2 signaling in the PCB neuron and its electrical partner, HOA. The glutamate-gated chloride channel AVR-14 is expressed in HOA. Our analysis of the unc-7 mutant allele indicates that when DOP-2 promotes UNC-7 electrical communication, AVR-14-mediated inhibitory signals pass from HOA to PCB. As a consequence, PCB is less receptive to be stimulated by its recurrent synaptic partner, PCA. Behavioral observations suggest that dopamine neuromodulation of UNC-7 ensures attenuation of recursive intromission attempts when the male disengages or is dislodged from the hermaphrodite genitalia. SIGNIFICANCE STATEMENT Using C. elegans male copulation as a model, we found that the neurotransmitter dopamine stimulates D2-like receptors in two sensory circuits to terminate futile behavioral loops. The D2-like receptors promote inhibitory electrical junction activity between a chemosensory and a mechanosensory circuit. Therefore, both systems are attenuated and the animal ceases the recursive behavior. PMID:26156999

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer.

PubMed

Zhao, Yiru Chen; Madak Erdogan, Zeynep

2016-03-17

With the advent of the -omics approaches our understanding of the chronic diseases like cancer and metabolic syndrome has improved. However, effective mining of the information in the large-scale datasets that are obtained from gene expression microarrays, deep sequencing experiments or metabolic profiling is essential to uncover and then effectively target the critical regulators of diseased cell phenotypes. Estrogen Receptor α (ERα) is one of the master transcription factors regulating the gene programs that are important for estrogen responsive breast cancers. In order to understand to role of ERα signaling in breast cancer metabolism we utilized transcriptomic, cistromic and metabolomic data from MCF-7 cells treated with estradiol. In this report we described generation of samples for RNA-Seq, ChIP-Seq and metabolomics experiments and the integrative computational analysis of the obtained data. This approach is useful in delineating novel molecular mechanisms and gene regulatory circuits that are regulated by a particular transcription factor which impacts metabolism of normal or diseased cells.

The Pleiotropic MET Receptor Network: Circuit Development and the Neural-Medical Interface of Autism

PubMed Central

Eagleson, Kathie L.; Xie, Zhihui; Levitt, Pat

2016-01-01

People with autism spectrum disorder (ASD) and other neurodevelopmental disorders (NDDs) are behaviorally and medically heterogeneous. The combination of polygenicity and gene pleiotropy - the influence of one gene on distinct phenotypes - raises questions of how specific genes and their protein products interact to contribute to NDDs. A preponderance of evidence supports developmental and pathophysiological roles for the MET receptor tyrosine kinase, a multi-functional receptor that mediates distinct biological responses depending upon cell context. MET influences neuron architecture and synapse maturation in the forebrain, and regulates homeostasis in gastrointestinal and immune systems, both commonly disrupted in NDDs. Peak expression of synapse-enriched MET is conserved across rodent and primate forebrain, yet regional differences in primate neocortex are pronounced, with enrichment in circuits that participate in social information processing. A functional risk allele in the MET promoter, enriched in subgroups of children with ASD, reduces transcription and disrupts socially-relevant neural circuits structurally and functionally. In mice, circuit-specific deletion of Met causes distinct atypical behaviors. MET activation increases dendritic complexity and nascent synapse number, but synapse maturation requires reductions in MET. MET mediates its specific biological effects through different intracellular signaling pathways, and has a complex protein interactome that is enriched in ASD and other NDD candidates. The interactome is co-regulated in developing human neocortex. We suggest that a gene as pleiotropic and highly regulated as MET, together with its interactome, is biologically relevant in normal and pathophysiological contexts, impacting central and peripheral phenotypes that contribute to NDD risk and clinical symptoms. PMID:27837921

An Eph receptor sperm-sensing control mechanism for oocyte meiotic maturation in Caenorhabditis elegans.

PubMed

Miller, Michael A; Ruest, Paul J; Kosinski, Mary; Hanks, Steven K; Greenstein, David

2003-01-15

During sexual reproduction in most animals, oocytes arrest in meiotic prophase and resume meiosis (meiotic maturation) in response to sperm or somatic cell signals. Despite progress in delineating mitogen-activated protein kinase (MAPK) and CDK/cyclin activation pathways involved in meiotic maturation, it is less clear how these pathways are regulated at the cell surface. The Caenorhabditis elegans major sperm protein (MSP) signals oocytes, which are arrested in meiotic prophase, to resume meiosis and ovulate. We used DNA microarray data and an in situ binding assay to identify the VAB-1 Eph receptor protein-tyrosine kinase as an MSP receptor. We show that VAB-1 and a somatic gonadal sheath cell-dependent pathway, defined by the CEH-18 POU-class homeoprotein, negatively regulate meiotic maturation and MAPK activation. MSP antagonizes these inhibitory signaling circuits, in part by binding VAB-1 on oocytes and sheath cells. Our results define a sperm-sensing control mechanism that inhibits oocyte maturation, MAPK activation, and ovulation when sperm are unavailable for fertilization. MSP-domain proteins are found in diverse animal taxa, where they may regulate contact-dependent Eph receptor signaling pathways.

Effect of Notch and PARP Pathways' Inhibition in Leukemic Cells.

PubMed

Horvat, Luka; Antica, Mariastefania; Matulić, Maja

2018-06-14

Differentiation of blood cells is one of the most complex processes in the body. It is regulated by the action of transcription factors in time and space which creates a specific signaling network. In the hematopoietic signaling system, Notch is one of the main regulators of lymphocyte development. The aim of this study was to get insight into the regulation of Notch signalization and the influence of poly(ADP-ribose)polymerase (PARP) activity on this process in three leukemia cell lines obtained from B and T cells. PARP1 is an enzyme involved in posttranslational protein modification and chromatin structure changes. B and T leukemia cells were treated with Notch and PARP inhibitors, alone or in combination, for a prolonged period. The cells did not show cell proliferation arrest or apoptosis. Analysis of gene and protein expression set involved in Notch and PARP pathways revealed increase in JAGGED1 expression after PARP1 inhibition in B cell lines and changes in Ikaros family members in both B and T cell lines after γ-secretase inhibition. These data indicate that Notch and PARP inhibition, although not inducing differentiation in leukemia cells, induce changes in signaling circuits and chromatin modelling factors.

DC isolation and protection system and circuit

NASA Technical Reports Server (NTRS)

Wagner, Charles A. (Inventor); Kellogg, Gary V. (Inventor)

1991-01-01

A precision analog electronic circuit that is capable of sending accurate signals to an external device that has hostile electric characteristics, including the presence of very large common mode voltages. The circuit is also capable of surviving applications of normal mode overvoltages of up to 120 VAC/VDC for unlimited periods of time without damage or degradation. First, the circuit isolates the DC signal output from the computer. Means are then provided for amplifying the isolated DC signal. Further means are provided for stabilizing and protecting the isolating and amplifying means, and the isolated and amplified DC signal which is output to the external device, against overvoltages and overcurrents.

Circuit for measuring time differences among events

DOEpatents

Romrell, Delwin M.

1977-01-01

An electronic circuit has a plurality of input terminals. Application of a first input signal to any one of the terminals initiates a timing sequence. Later inputs to the same terminal are ignored but a later input to any other terminal of the plurality generates a signal which can be used to measure the time difference between the later input and the first input signal. Also, such time differences may be measured between the first input signal and an input signal to any other terminal of the plurality or the circuit may be reset at any time by an external reset signal.

Electronic Circuit Experiments and SPICE Simulation of Double Covering Bifurcation of 2-Torus Quasi-Periodic Flow in Phase-Locked Loop Circuit

NASA Astrophysics Data System (ADS)

Kamiyama, Kyohei; Endo, Tetsuro; Imai, Isao; Komuro, Motomasa

2016-06-01

Double covering (DC) bifurcation of a 2-torus quasi-periodic flow in a phase-locked loop circuit was experimentally investigated using an electronic circuit and via SPICE simulation; in the circuit, the input radio-frequency signal was frequency modulated by the sum of two asynchronous sinusoidal baseband signals. We observed both DC and period-doubling bifurcations of a discrete map on two Poincaré sections, which were realized by changing the sample timing from one baseband sinusoidal signal to the other. The results confirm the DC bifurcation of the original flow.

Circuit for Communication over DC Power Line Using High Temperature Electronics

NASA Technical Reports Server (NTRS)

Krasowski, Michael J. (Inventor); Prokop, Norman F. (Inventor)

2014-01-01

A high temperature communications circuit includes a power conductor for concurrently conducting electrical energy for powering circuit components and transmitting a modulated data signal, and a demodulator for demodulating the data signal and generating a serial bit stream based on the data signal. The demodulator includes an absolute value amplifier for conditionally inverting or conditionally passing a signal applied to the absolute value amplifier. The absolute value amplifier utilizes no diodes to control the conditional inversion or passing of the signal applied to the absolute value amplifier.

Postnatal Ablation of Synaptic Retinoic Acid Signaling Impairs Cortical Information Processing and Sensory Discrimination in Mice.

PubMed

Park, Esther; Tjia, Michelle; Zuo, Yi; Chen, Lu

2018-06-06

Retinoic acid (RA) and its receptors (RARs) are well established essential transcriptional regulators during embryonic development. Recent findings in cultured neurons identified an independent and critical post-transcriptional role of RA and RARα in the homeostatic regulation of excitatory and inhibitory synaptic transmission in mature neurons. However, the functional relevance of synaptic RA signaling in vivo has not been established. Here, using somatosensory cortex as a model system and the RARα conditional knock-out mouse as a tool, we applied multiple genetic manipulations to delete RARα postnatally in specific populations of cortical neurons, and asked whether synaptic RA signaling observed in cultured neurons is involved in cortical information processing in vivo Indeed, conditional ablation of RARα in mice via a CaMKIIα-Cre or a layer 5-Cre driver line or via somatosensory cortex-specific viral expression of Cre-recombinase impaired whisker-dependent texture discrimination, suggesting a critical requirement of RARα expression in L5 pyramidal neurons of somatosensory cortex for normal tactile sensory processing. Transcranial two-photon imaging revealed a significant increase in dendritic spine elimination on apical dendrites of somatosensory cortical layer 5 pyramidal neurons in these mice. Interestingly, the enhancement of spine elimination is whisker experience-dependent as whisker trimming rescued the spine elimination phenotype. Additionally, experiencing an enriched environment improved texture discrimination in RARα-deficient mice and reduced excessive spine pruning. Thus, RA signaling is essential for normal experience-dependent cortical circuit remodeling and sensory processing. SIGNIFICANCE STATEMENT The importance of synaptic RA signaling has been demonstrated in in vitro studies. However, whether RA signaling mediated by RARα contributes to neural circuit functions in vivo remains largely unknown. In this study, using a RARα conditional knock-out mouse, we performed multiple regional/cell-type-specific manipulation of RARα expression in the postnatal brain, and show that RARα signaling contributes to normal whisker-dependent texture discrimination as well as regulating spine dynamics of apical dendrites from layer (L5) pyramidal neurons in S1. Deletion of RARα in excitatory neurons in the forebrain induces elevated spine elimination and impaired sensory discrimination. Our study provides novel insights into the role of RARα signaling in cortical processing and experience-dependent spine maturation. Copyright © 2018 the authors 0270-6474/18/385277-12$15.00/0.

FREQUENCY STABILIZING SYSTEM

DOEpatents

Kerns, Q.A.; Anderson, O.A.

1960-05-01

An electronic control circuit is described in which a first signal frequency is held in synchronization with a second varying reference signal. The circuit receives the first and second signals as inputs and produces an output signal having an amplitude dependent upon rate of phase change between the two signals and a polarity dependent on direction of the phase change. The output may thus serve as a correction signal for maintaining the desired synchronization. The response of the system is not dependent on relative phase angle between the two compared signals. By having practically no capacitance in the circuit, there is minimum delay between occurrence of a phase shift and a response in the output signal and therefore very fast synchronization is effected.

Non-homeostatic body weight regulation through a brainstem-restricted receptor for GDF15

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

Hsu, Jer-Yuan; Crawley, Suzanne; Chen, Michael

Under homeostatic conditions, animals use well-defined hypothalamic neural circuits to help maintain stable body weight, by integrating metabolic and hormonal signals from the periphery to balance food consumption and energy expenditure1,2. In stressed or disease conditions, however, animals use alternative neuronal pathways to adapt to the metabolic challenges of altered energy demand3. Recent studies have identified brain areas outside the hypothalamus that are activated under these ‘non-homeostatic’ conditions4,5,6, but the molecular nature of the peripheral signals and brain-localized receptors that activate these circuits remains elusive. Here we identify glial cell-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL) as a brainstem-restricted receptormore » for growth and differentiation factor 15 (GDF15). GDF15 regulates food intake, energy expenditure and body weight in response to metabolic and toxin-induced stresses; we show that Gfral knockout mice are hyperphagic under stressed conditions and are resistant to chemotherapy-induced anorexia and body weight loss. GDF15 activates GFRAL-expressing neurons localized exclusively in the area postrema and nucleus tractus solitarius of the mouse brainstem. It then triggers the activation of neurons localized within the parabrachial nucleus and central amygdala, which constitute part of the ‘emergency circuit’ that shapes feeding responses to stressful conditions7. GDF15 levels increase in response to tissue stress and injury, and elevated levels are associated with body weight loss in numerous chronic human diseases8,9. By isolating GFRAL as the receptor for GDF15-induced anorexia and weight loss, we identify a mechanistic basis for the non-homeostatic regulation of neural circuitry by a peripheral signal associated with tissue damage and stress. These findings provide opportunities to develop therapeutic agents for the treatment of disorders with altered energy demand.« less

Kainate Receptors Inhibit Glutamate Release Via Mobilization of Endocannabinoids in Striatal Direct Pathway Spiny Projection Neurons.

PubMed

Marshall, John J; Xu, Jian; Contractor, Anis

2018-04-18

Kainate receptors are members of the glutamate receptor family that function by both generating ionotropic currents through an integral ion channel pore and coupling to downstream metabotropic signaling pathways. They are highly expressed in the striatum, yet their roles in regulating striatal synapses are not known. Using mice of both sexes, we demonstrate that GluK2-containing kainate receptors expressed in direct pathway spiny projection neurons (dSPNs) inhibit glutamate release at corticostriatal synapses in the dorsolateral striatum. This inhibition requires postsynaptic kainate-receptor-mediated mobilization of a retrograde endocannabinoid (eCB) signal and activation of presynaptic CB1 receptors. This pathway can be activated during repetitive 25 Hz trains of synaptic stimulation, causing short-term depression of corticostriatal synapses. This is the first study to demonstrate a role for kainate receptors in regulating eCB-mediated plasticity at the corticostriatal synapse and demonstrates an important role for these receptors in regulating basal ganglia circuits. SIGNIFICANCE STATEMENT The GRIK2 gene, encoding the GluK2 subunit of the kainate receptor, has been linked to several neuropsychiatric and neurodevelopmental disorders including obsessive compulsive disorder (OCD). Perseverative behaviors associated with OCD are known to result from pathophysiological changes in the striatum and kainate receptor knock-out mice have striatal-dependent phenotypes. However, the role of kainate receptors in striatal synapses is not known. We demonstrate that GluK2-containing kainate receptors regulate corticostriatal synapses by mobilizing endocannabinoids from direct pathway spiny projection neurons. Synaptic activation of GluK2 receptors during trains of synaptic input causes short-term synaptic depression, demonstrating a novel role for these receptors in regulating striatal circuits. Copyright © 2018 the authors 0270-6474/18/383901-10$15.00/0.

A Feedforward Inhibitory Circuit Mediated by CB1-Expressing Fast-Spiking Interneurons in the Nucleus Accumbens.

PubMed

Wright, William J; Schlüter, Oliver M; Dong, Yan

2017-04-01

The nucleus accumbens (NAc) gates motivated behaviors through the functional output of principle medium spiny neurons (MSNs), whereas dysfunctional output of NAc MSNs contributes to a variety of psychiatric disorders. Fast-spiking interneurons (FSIs) are sparsely distributed throughout the NAc, forming local feedforward inhibitory circuits. It remains elusive how FSI-based feedforward circuits regulate the output of NAc MSNs. Here, we investigated a distinct subpopulation of NAc FSIs that express the cannabinoid receptor type-1 (CB1). Using a combination of paired electrophysiological recordings and pharmacological approaches, we characterized and compared feedforward inhibition of NAc MSNs from CB1 + FSIs and lateral inhibition from recurrent MSN collaterals. We observed that CB1 + FSIs exerted robust inhibitory control over a large percentage of nearby MSNs in contrast to local MSN collaterals that provided only sparse and weak inhibitory input to their neighboring MSNs. Furthermore, CB1 + FSI-mediated feedforward inhibition was preferentially suppressed by endocannabinoid (eCB) signaling, whereas MSN-mediated lateral inhibition was unaffected. Finally, we demonstrated that CB1 + FSI synapses onto MSNs are capable of undergoing experience-dependent long-term depression in a voltage- and eCB-dependent manner. These findings demonstrated that CB1 + FSIs are a major source of local inhibitory control of MSNs and a critical component of the feedforward inhibitory circuits regulating the output of the NAc.

A Feedforward Inhibitory Circuit Mediated by CB1-Expressing Fast-Spiking Interneurons in the Nucleus Accumbens

PubMed Central

Wright, William J; Schlüter, Oliver M; Dong, Yan

2017-01-01

The nucleus accumbens (NAc) gates motivated behaviors through the functional output of principle medium spiny neurons (MSNs), whereas dysfunctional output of NAc MSNs contributes to a variety of psychiatric disorders. Fast-spiking interneurons (FSIs) are sparsely distributed throughout the NAc, forming local feedforward inhibitory circuits. It remains elusive how FSI-based feedforward circuits regulate the output of NAc MSNs. Here, we investigated a distinct subpopulation of NAc FSIs that express the cannabinoid receptor type-1 (CB1). Using a combination of paired electrophysiological recordings and pharmacological approaches, we characterized and compared feedforward inhibition of NAc MSNs from CB1+ FSIs and lateral inhibition from recurrent MSN collaterals. We observed that CB1+ FSIs exerted robust inhibitory control over a large percentage of nearby MSNs in contrast to local MSN collaterals that provided only sparse and weak inhibitory input to their neighboring MSNs. Furthermore, CB1+ FSI-mediated feedforward inhibition was preferentially suppressed by endocannabinoid (eCB) signaling, whereas MSN-mediated lateral inhibition was unaffected. Finally, we demonstrated that CB1+ FSI synapses onto MSNs are capable of undergoing experience-dependent long-term depression in a voltage- and eCB-dependent manner. These findings demonstrated that CB1+ FSIs are a major source of local inhibitory control of MSNs and a critical component of the feedforward inhibitory circuits regulating the output of the NAc. PMID:27929113

Myelination and mTOR

PubMed Central

Figlia, Gianluca; Gerber, Daniel

2017-01-01

Abstract Myelinating cells surround axons to accelerate the propagation of action potentials, to support axonal health, and to refine neural circuits. Myelination is metabolically demanding and, consistent with this notion, mTORC1—a signaling hub coordinating cell metabolism—has been implicated as a key signal for myelination. Here, we will discuss metabolic aspects of myelination, illustrate the main metabolic processes regulated by mTORC1, and review advances on the role of mTORC1 in myelination of the central nervous system and the peripheral nervous system. Recent progress has revealed a complex role of mTORC1 in myelinating cells that includes, besides positive regulation of myelin growth, additional critical functions in the stages preceding active myelination. Based on the available evidence, we will also highlight potential nonoverlapping roles between mTORC1 and its known main upstream pathways PI3K‐Akt, Mek‐Erk1/2, and AMPK in myelinating cells. Finally, we will discuss signals that are already known or hypothesized to be responsible for the regulation of mTORC1 activity in myelinating cells. PMID:29210103

Cryogenic Pound Circuits for Cryogenic Sapphire Oscillators

NASA Technical Reports Server (NTRS)

Dick, G. John; Wang, Rabi

2006-01-01

Two modern cryogenic variants of the Pound circuit have been devised to increase the frequency stability of microwave oscillators that include cryogenic sapphire-filled cavity resonators. The original Pound circuit is a microwave frequency discriminator that provides feedback to stabilize a voltage-controlled microwave oscillator with respect to an associated cavity resonator. In the present cryogenic Pound circuits, the active microwave devices are implemented by use of state-of-the-art commercially available tunnel diodes that exhibit low flicker noise (required for high frequency stability) and function well at low temperatures and at frequencies up to several tens of gigahertz. While tunnel diodes are inherently operable as amplitude detectors and amplitude modulators, they cannot, by themselves, induce significant phase modulation. Therefore, each of the present cryogenic Pound circuits includes passive circuitry that transforms the AM into the required PM. Each circuit also contains an AM detector that is used to sample the microwave signal at the input terminal of the high-Q resonator for the purpose of verifying the desired AM null at this point. Finally, each circuit contains a Pound signal detector that puts out a signal, at the modulation frequency, having an amplitude proportional to the frequency error in the input signal. High frequency stability is obtained by processing this output signal into feedback to a voltage-controlled oscillator to continuously correct the frequency error in the input signal.

Switching-type regulator circuit has increased efficiency

NASA Technical Reports Server (NTRS)

Clapp, W. M.

1967-01-01

Switching series regulator circuit uses an inductive network to feed most of the current applied to the control circuit to the load. This circuit eliminates resistive losses and the need for heat sinks.

Overload protection circuit for output driver

DOEpatents

Stewart, Roger G.

1982-05-11

A protection circuit for preventing excessive power dissipation in an output transistor whose conduction path is connected between a power terminal and an output terminal. The protection circuit includes means for sensing the application of a turn on signal to the output transistor and the voltage at the output terminal. When the turn on signal is maintained for a period of time greater than a given period without the voltage at the output terminal reaching a predetermined value, the protection circuit decreases the turn on signal to, and the current conduction through, the output transistor.

Full-Circle Resolver-to-Linear-Analog Converter

NASA Technical Reports Server (NTRS)

Alhorn, Dean C.; Smith, Dennis A.; Howard, David E.

2005-01-01

A circuit generates sinusoidal excitation signals for a shaft-angle resolver and, like the arctangent circuit described in the preceding article, generates an analog voltage proportional to the shaft angle. The disadvantages of the circuit described in the preceding article arise from the fact that it must be made from precise analog subcircuits, including a functional block capable of implementing some trigonometric identities; this circuitry tends to be expensive, sensitive to noise, and susceptible to errors caused by temperature-induced drifts and imprecise matching of gains and phases. These disadvantages are overcome by the design of the present circuit. The present circuit (see figure) includes an excitation circuit, which generates signals Ksin(Omega(t)) and Kcos(Omega(t)) [where K is an amplitude, Omega denotes 2(pi)x a carrier frequency (the design value of which is 10 kHz), and t denotes time]. These signals are applied to the excitation terminals of a shaft-angle resolver, causing the resolver to put out signals C sin(Omega(t)-Theta) and C cos(Omega(t)-Theta). The cosine excitation signal and the cosine resolver output signal are processed through inverting comparator circuits, which are configured to function as inverting squarers, to obtain logic-level or square-wave signals .-LL[cos(Omega(t)] and -LL[cos(Omega(t)-Theta)], respectively. These signals are fed as inputs to a block containing digital logic circuits that effectively measure the phase difference (which equals Theta between the two logic-level signals). The output of this block is a pulse-width-modulated signal, PWM(Theta), the time-averaged value of which ranges from 0 to 5 VDC as Theta ranges from .180 to +180deg. PWM(Theta) is fed to a block of amplifying and level-shifting circuitry, which converts the input PWM waveform to an output waveform that switches between precise reference voltage levels of +10 and -10 V. This waveform is processed by a two-pole, low-pass filter, which removes the carrier-frequency component. The final output signal is a DC potential, proportional to Theta that ranges continuously from -10 V at Theta = -180deg to +10 V at Theta = +180deg..

Automatic control of liquid cooling garment by cutaneous and external auditory meatus temperatures

NASA Technical Reports Server (NTRS)

Fulcher, C. W. G. (Inventor)

1971-01-01

An automatic control apparatus for a liquid cooling garment is described that is responsive to actual physiological needs during work and rest periods of a man clothed in the liquid cooling garment. Four skin temperature readings and a reading taken at the external portion of the auditory meatus are added and used in the control signal for a temperature control valve regulating inlet water temperature for the liquid cooling garment. The control apparatus comprises electronic circuits to which the temperatures are applied as control signals and an electro-pneumatic transducer attached to the control valve.

Probabilistic switching circuits in DNA

PubMed Central

Wilhelm, Daniel; Bruck, Jehoshua

2018-01-01

A natural feature of molecular systems is their inherent stochastic behavior. A fundamental challenge related to the programming of molecular information processing systems is to develop a circuit architecture that controls the stochastic states of individual molecular events. Here we present a systematic implementation of probabilistic switching circuits, using DNA strand displacement reactions. Exploiting the intrinsic stochasticity of molecular interactions, we developed a simple, unbiased DNA switch: An input signal strand binds to the switch and releases an output signal strand with probability one-half. Using this unbiased switch as a molecular building block, we designed DNA circuits that convert an input signal to an output signal with any desired probability. Further, this probability can be switched between 2n different values by simply varying the presence or absence of n distinct DNA molecules. We demonstrated several DNA circuits that have multiple layers and feedback, including a circuit that converts an input strand to an output strand with eight different probabilities, controlled by the combination of three DNA molecules. These circuits combine the advantages of digital and analog computation: They allow a small number of distinct input molecules to control a diverse signal range of output molecules, while keeping the inputs robust to noise and the outputs at precise values. Moreover, arbitrarily complex circuit behaviors can be implemented with just a single type of molecular building block. PMID:29339484

A spatially localized architecture for fast and modular DNA computing

NASA Astrophysics Data System (ADS)

Chatterjee, Gourab; Dalchau, Neil; Muscat, Richard A.; Phillips, Andrew; Seelig, Georg

2017-09-01

Cells use spatial constraints to control and accelerate the flow of information in enzyme cascades and signalling networks. Synthetic silicon-based circuitry similarly relies on spatial constraints to process information. Here, we show that spatial organization can be a similarly powerful design principle for overcoming limitations of speed and modularity in engineered molecular circuits. We create logic gates and signal transmission lines by spatially arranging reactive DNA hairpins on a DNA origami. Signal propagation is demonstrated across transmission lines of different lengths and orientations and logic gates are modularly combined into circuits that establish the universality of our approach. Because reactions preferentially occur between neighbours, identical DNA hairpins can be reused across circuits. Co-localization of circuit elements decreases computation time from hours to minutes compared to circuits with diffusible components. Detailed computational models enable predictive circuit design. We anticipate our approach will motivate using spatial constraints for future molecular control circuit designs.

High temperature charge amplifier for geothermal applications

DOEpatents

Lindblom, Scott C.; Maldonado, Frank J.; Henfling, Joseph A.

2015-12-08

An amplifier circuit in a multi-chip module includes a charge to voltage converter circuit, a voltage amplifier a low pass filter and a voltage to current converter. The charge to voltage converter receives a signal representing an electrical charge and generates a voltage signal proportional to the input signal. The voltage amplifier receives the voltage signal from the charge to voltage converter, then amplifies the voltage signal by the gain factor to output an amplified voltage signal. The lowpass filter passes low frequency components of the amplified voltage signal and attenuates frequency components greater than a cutoff frequency. The voltage to current converter receives the output signal of the lowpass filter and converts the output signal to a current output signal; wherein an amplifier circuit output is selectable between the output signal of the lowpass filter and the current output signal.

Investigation into the common mode rejection ratio of the physiological signal conditioner circuit

NASA Technical Reports Server (NTRS)

Obrien, Edward M.

1992-01-01

The common mode rejection ratio (CMRR) of the single operational amplifier (op amp) differential amplifier and of the three operational amplifier differential amplifier was investigated. The three op amp differential amplifier circuit is used in the signal conditioner circuit which amplifies signals such as the electromyograph or electrocardiogram. The investigation confirmed via SPICE modeling what has been observed by others in the recent literature that the CMRR for the circuit can be maximized without precision resistor values or precisely matched op amps. This can be done if one resistor in the final stage can be adjusted either by a potentiometer or by laser trimming in the case of hybrid circuit fabrication.

System and circuitry to provide stable transconductance for biasing

NASA Technical Reports Server (NTRS)

Garverick, Steven L. (Inventor); Yu, Xinyu (Inventor)

2012-01-01

An amplifier system can include an input amplifier configured to receive an analog input signal and provide an amplified signal corresponding to the analog input signal. A tracking loop is configured to employ delta modulation for tracking the amplified signal, the tracking loop providing a corresponding output signal. A biasing circuit is configured to adjust a bias current to maintain stable transconductance over temperature variations, the biasing circuit providing at least one bias signal for biasing at least one of the input amplifier and the tracking loop, whereby the circuitry receiving the at least one bias signal exhibits stable performance over the temperature variations. In another embodiment the biasing circuit can be utilized in other applications.

Modular high voltage power supply for chemical analysis

DOEpatents

Stamps, James F [Livermore, CA; Yee, Daniel D [Dublin, CA

2007-01-09

A high voltage power supply for use in a system such as a microfluidics system, uses a DC--DC converter in parallel with a voltage-controlled resistor. A feedback circuit provides a control signal for the DC--DC converter and voltage-controlled resistor so as to regulate the output voltage of the high voltage power supply, as well as, to sink or source current from the high voltage supply.

Modular high voltage power supply for chemical analysis

DOEpatents

Stamps, James F [Livermore, CA; Yee, Daniel D [Dublin, CA

2010-05-04

A high voltage power supply for use in a system such as a microfluidics system, uses a DC-DC converter in parallel with a voltage-controlled resistor. A feedback circuit provides a control signal for the DC-DC converter and voltage-controlled resistor so as to regulate the output voltage of the high voltage power supply, as well as, to sink or source current from the high voltage supply.

Modular high voltage power supply for chemical analysis

DOEpatents

Stamps, James F [Livermore, CA; Yee, Daniel D [Dublin, CA

2008-07-15

A high voltage power supply for use in a system such as a microfluidics system, uses a DC-DC converter in parallel with a voltage-controlled resistor. A feedback circuit provides a control signal for the DC-DC converter and voltage-controlled resistor so as to regulate the output voltage of the high voltage power supply, as well as, to sink or source current from the high voltage supply.

Increasing Signal Specificity of the TOL Network of Pseudomonas putida mt-2 by Rewiring the Connectivity of the Master Regulator XylR

PubMed Central

de las Heras, Aitor; Fraile, Sofia; de Lorenzo, Victor

2012-01-01

Prokaryotic transcription factors (TFs) that bind small xenobiotic molecules (e.g., TFs that drive genes that respond to environmental pollutants) often display a promiscuous effector profile for analogs of the bona fide chemical signals. XylR, the master TF for expression of the m-xylene biodegradation operons encoded in the TOL plasmid pWW0 of Pseudomonas putida, responds not only to the aromatic compound but also, albeit to a lesser extent, to many other aromatic compounds, such as 3-methylbenzylalcohol (3MBA). We have examined whether such a relaxed regulatory scenario can be reshaped into a high-capacity/high-specificity regime by changing the connectivity of this effector-sensing TF within the rest of the circuit rather than modifying XylR structure itself. To this end, the natural negative feedback loop that operates on xylR transcription was modified with a translational attenuator that brings down the response to 3MBA while maintaining the transcriptional output induced by m-xylene (as measured with a luxCDABE reporter system). XylR expression was then subject to a positive feedback loop in which the TF was transcribed from its own target promoters, each known to hold different input/output transfer functions. In the first case (xylR under the strong promoter of the upper TOL operon, Pu), the reporter system displayed an increased transcriptional capacity in the resulting network for both the optimal and the suboptimal XylR effectors. In contrast, when xylR was expressed under the weaker Ps promoter, the resulting circuit unmistakably discriminated m-xylene from 3MBA. The non-natural connectivity engineered in the network resulted both in a higher promoter activity and also in a much-increased signal-to-background ratio. These results indicate that the working regimes of given genetic circuits can be dramatically altered through simple changes in the way upstream transcription factors are self-regulated by positive or negative feedback loops. PMID:23071444

Microfluidic study of environmental control of genetic competence in Streptococcus mutans

NASA Astrophysics Data System (ADS)

Son, Minjun; Ghoreishilangroudi, Seyedehdelaram; Ahn, Sang-Joon; Burne, Robert; Hagen, Stephen

2015-03-01

The bacterial pathogen Streptococcus mutans has the ability to enter a transient state of genetic competence in which it can integrate exogenous DNA. It regulates the competent state in response to several environmental inputs that include two quorum sensing peptides (CSP and XIP) as well as pH and other variables. However the interplay of these variables in regulating the competent state is poorly understood. We are using microfluidics to isolate and control environmental inputs and examine how the competence regulatory circuit responds at the single cell level. Our studies reveal that the pH of the growth environment plays a critical role in determining how cells respond to the quorum sensing signals: The response to both peptides is sharply tuned to a narrow window of near-neutral pH. Within this optimal pH range, a population responds unimodally to a XIP stimulus, and bimodally to CSP; outside this range the response to both signals is suppressed. Because a growing S. mutans culture acidifies its medium, our findings suggest that the passage of the pH through the sensitivity window transiently activates the competence circuit. In this way a sharply tuned environmental response gives S. mutans fine control over the duration of its competent state. This work is supported by the NIH under NIDCR awards R01 DE023339.

Scaling up digital circuit computation with DNA strand displacement cascades.

PubMed

Qian, Lulu; Winfree, Erik

2011-06-03

To construct sophisticated biochemical circuits from scratch, one needs to understand how simple the building blocks can be and how robustly such circuits can scale up. Using a simple DNA reaction mechanism based on a reversible strand displacement process, we experimentally demonstrated several digital logic circuits, culminating in a four-bit square-root circuit that comprises 130 DNA strands. These multilayer circuits include thresholding and catalysis within every logical operation to perform digital signal restoration, which enables fast and reliable function in large circuits with roughly constant switching time and linear signal propagation delays. The design naturally incorporates other crucial elements for large-scale circuitry, such as general debugging tools, parallel circuit preparation, and an abstraction hierarchy supported by an automated circuit compiler.

Experimental industrial signal acquisition board in a large scientific device

NASA Astrophysics Data System (ADS)

Zeng, Xiangzhen; Ren, Bin

2018-02-01

In order to measure the industrial signal of neutrino experiment, a set of general-purpose industrial data acquisition board has been designed. It includes the function of switch signal input and output, and the function of analog signal input. The main components are signal isolation amplifier and filter circuit, ADC circuit, microcomputer systems and isolated communication interface circuit. Through the practical experiments, it shows that the system is flexible, reliable, convenient and economical, and the system has characters of high definition and strong anti-interference ability. Thus, the system fully meets the design requirements.

Method and apparatus for granting processors access to a resource

DOEpatents

Blumrich, Matthias A.; Salapura, Valentina

2010-03-16

An apparatus and method for granting one or more requesting entities access to a resource in a predetermined time interval. The apparatus includes a first circuit receiving one or more request signals, and implementing logic for assigning a priority to the one or more request signals, and, generating a set of first_request signals based on the priorities assigned. One or more priority select circuits for receiving the set of first_request signals and generating corresponding one or more fixed grant signals representing one or more highest priority request signals when asserted during the predetermined time interval. A second circuit device receives the one or more fixed grant signals generates one or more grant signals associated with one or more highest priority request signals assigned, the grant signals for enabling one or more respective requesting entities access to the resource in the predetermined time interval, wherein the priority assigned to the one or more request signals changes each successive predetermined time interval. In one embodiment, the assigned priority is based on a numerical pattern, the first circuit changing the numerical pattern with respect to the first_request signals generated at each successive predetermined time interval.

On the Role of Glutamate in Presynaptic Development: Possible Contributions of Presynaptic NMDA Receptors.

PubMed

Fedder, Karlie N; Sabo, Shasta L

2015-12-14

Proper formation and maturation of synapses during development is a crucial step in building the functional neural circuits that underlie perception and behavior. It is well established that experience modifies circuit development. Therefore, understanding how synapse formation is controlled by synaptic activity is a key question in neuroscience. In this review, we focus on the regulation of excitatory presynaptic terminal development by glutamate, the predominant excitatory neurotransmitter in the brain. We discuss the evidence that NMDA receptor activation mediates these effects of glutamate and present the hypothesis that local activation of presynaptic NMDA receptors (preNMDARs) contributes to glutamate-dependent control of presynaptic development. Abnormal glutamate signaling and aberrant synapse development are both thought to contribute to the pathogenesis of a variety of neurodevelopmental disorders, including autism spectrum disorders, intellectual disability, epilepsy, anxiety, depression, and schizophrenia. Therefore, understanding how glutamate signaling and synapse development are linked is important for understanding the etiology of these diseases.

Complete Disruption of the Kainate Receptor Gene Family Results in Corticostriatal Dysfunction in Mice.

PubMed

Xu, Jian; Marshall, John J; Fernandes, Herman B; Nomura, Toshihiro; Copits, Bryan A; Procissi, Daniele; Mori, Susumu; Wang, Lei; Zhu, Yongling; Swanson, Geoffrey T; Contractor, Anis

2017-02-21

Kainate receptors are members of the glutamate receptor family that regulate synaptic function in the brain. They modulate synaptic transmission and the excitability of neurons; however, their contributions to neural circuits that underlie behavior are unclear. To understand the net impact of kainate receptor signaling, we generated knockout mice in which all five kainate receptor subunits were ablated (5ko). These mice displayed compulsive and perseverative behaviors, including over-grooming, as well as motor problems, indicative of alterations in striatal circuits. There were deficits in corticostriatal input to spiny projection neurons (SPNs) in the dorsal striatum and correlated reductions in spine density. The behavioral alterations were not present in mice only lacking the primary receptor subunit expressed in adult striatum (GluK2 KO), suggesting that signaling through multiple receptor types is required for proper striatal function. This demonstrates that alterations in striatal function dominate the behavioral phenotype in mice without kainate receptors. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

A High-Temperature Piezoresistive Pressure Sensor with an Integrated Signal-Conditioning Circuit.

PubMed

Yao, Zong; Liang, Ting; Jia, Pinggang; Hong, Yingping; Qi, Lei; Lei, Cheng; Zhang, Bin; Xiong, Jijun

2016-06-18

This paper focuses on the design and fabrication of a high-temperature piezoresistive pressure sensor with an integrated signal-conditioning circuit, which consists of an encapsulated pressure-sensitive chip, a temperature compensation circuit and a signal-conditioning circuit. A silicon on insulation (SOI) material and a standard MEMS process are used in the pressure-sensitive chip fabrication, and high-temperature electronic components are adopted in the temperature-compensation and signal-conditioning circuits. The entire pressure sensor achieves a hermetic seal and can be operated long-term in the range of -50 °C to 220 °C. Unlike traditional pressure sensor output voltage ranges (in the dozens to hundreds of millivolts), the output voltage of this sensor is from 0 V to 5 V, which can significantly improve the signal-to-noise ratio and measurement accuracy in practical applications of long-term transmission based on experimental verification. Furthermore, because this flexible sensor's output voltage is adjustable, general follow-up pressure transmitter devices for voltage converters need not be used, which greatly reduces the cost of the test system. Thus, the proposed high-temperature piezoresistive pressure sensor with an integrated signal-conditioning circuit is expected to be highly applicable to pressure measurements in harsh environments.

A High-Temperature Piezoresistive Pressure Sensor with an Integrated Signal-Conditioning Circuit

PubMed Central

Yao, Zong; Liang, Ting; Jia, Pinggang; Hong, Yingping; Qi, Lei; Lei, Cheng; Zhang, Bin; Xiong, Jijun

2016-01-01

This paper focuses on the design and fabrication of a high-temperature piezoresistive pressure sensor with an integrated signal-conditioning circuit, which consists of an encapsulated pressure-sensitive chip, a temperature compensation circuit and a signal-conditioning circuit. A silicon on insulation (SOI) material and a standard MEMS process are used in the pressure-sensitive chip fabrication, and high-temperature electronic components are adopted in the temperature-compensation and signal-conditioning circuits. The entire pressure sensor achieves a hermetic seal and can be operated long-term in the range of −50 °C to 220 °C. Unlike traditional pressure sensor output voltage ranges (in the dozens to hundreds of millivolts), the output voltage of this sensor is from 0 V to 5 V, which can significantly improve the signal-to-noise ratio and measurement accuracy in practical applications of long-term transmission based on experimental verification. Furthermore, because this flexible sensor’s output voltage is adjustable, general follow-up pressure transmitter devices for voltage converters need not be used, which greatly reduces the cost of the test system. Thus, the proposed high-temperature piezoresistive pressure sensor with an integrated signal-conditioning circuit is expected to be highly applicable to pressure measurements in harsh environments. PMID:27322288

Two-Component Signal Transduction Systems That Regulate the Temporal and Spatial Expression of Myxococcus xanthus Sporulation Genes.

PubMed

Sarwar, Zaara; Garza, Anthony G

2016-02-01

When starved for nutrients, Myxococcus xanthus produces a biofilm that contains a mat of rod-shaped cells, known as peripheral rods, and aerial structures called fruiting bodies, which house thousands of dormant and stress-resistant spherical spores. Because rod-shaped cells differentiate into spherical, stress-resistant spores and spore differentiation occurs only in nascent fruiting bodies, many genes and multiple levels of regulation are required. Over the past 2 decades, many regulators of the temporal and spatial expression of M. xanthus sporulation genes have been uncovered. Of these sporulation gene regulators, two-component signal transduction circuits, which typically contain a histidine kinase sensor protein and a transcriptional regulator known as response regulator, are among the best characterized. In this review, we discuss prototypical two-component systems (Nla6S/Nla6 and Nla28S/Nla28) that regulate an early, preaggregation phase of sporulation gene expression during fruiting body development. We also discuss orphan response regulators (ActB and FruA) that regulate a later phase of sporulation gene expression, which begins during the aggregation stage of fruiting body development. In addition, we summarize the research on a complex two-component system (Esp) that is important for the spatial regulation of sporulation. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

A novel function for Wnt signaling modulating neuronal firing activity and the temporal structure of spontaneous oscillation in the entorhinal-hippocampal circuit.

PubMed

Oliva, Carolina A; Inestrosa, Nibaldo C

2015-07-01

During early and late postnatal developments, the establishment of functional neuronal connectivity depends on molecules like Wnt that help the recently formed synapses to establish and consolidate their new cellular interactions. However, unlike other molecules, whether Wnt can modulate the firing properties of cells is unknown. Here, for the first time we explore the physiological effect of the canonical and non-canonical Wnt pathways on a circuit that is currently generating oscillatory activity, the entorhinal cortex-hippocampal circuit. Our results indicate that Wnt pathways have strong influence in the circuital and cellular properties depending on the Wnt protein isoforms, concentration, and type of neuronal circuit. Antibodies against canonical and non-canonical ligands, as well as WASP-1 and sFRP-2, demonstrate that constitutive release of Wnts contributes to the maintenance of the network and intrinsic properties of the circuit. Furthermore, we found that the excess of Wnt3a or the permanent intracellular activation of the pathway with BIO-6 accelerates the period of the oscillation by disrupting the oscillatory units (Up states) in short units, presumably by affecting the synaptic mechanisms that couples neurons into the oscillatory cycle, but without affecting the spike generation. Instead, low doses of Wnt5a increase the period of the oscillation in EC by incorporating new cells into the network activity, probably modifying firing activity in other places of the circuit. Moreover, we found that Wnt signaling operates under different principles in the hippocampus. Using pyrvinium pamoate, a Wnt/β-catenin dependent pathway inhibitor, we demonstrated that this pathway is essential to keep the firing activity in the circuit CA3, and in less degree of CA1 circuit. However, CA1 circuit possesses homeostatic mechanisms to up-regulate the firing activity when it has been suppressed in CA3, and to down-modulate the cellular excitability when exacerbated circuital activity has dominated. In summary, the amount of Wnt that is being released can exert a fine tuning of the physiological output, modulating firing activity, improving reliability of communication between neurons, and maintaining a continuous self-regulatory cycle of synaptic structure-function that can be present during all postnatal life. Copyright © 2015 Elsevier Inc. All rights reserved.

Regulation of signal transduction by reactive oxygen species in the cardiovascular system.

PubMed

Brown, David I; Griendling, Kathy K

2015-01-30

Oxidative stress has long been implicated in cardiovascular disease, but more recently, the role of reactive oxygen species (ROS) in normal physiological signaling has been elucidated. Signaling pathways modulated by ROS are complex and compartmentalized, and we are only beginning to identify the molecular modifications of specific targets. Here, we review the current literature on ROS signaling in the cardiovascular system, focusing on the role of ROS in normal physiology and how dysregulation of signaling circuits contributes to cardiovascular diseases, including atherosclerosis, ischemia-reperfusion injury, cardiomyopathy, and heart failure. In particular, we consider how ROS modulate signaling pathways related to phenotypic modulation, migration and adhesion, contractility, proliferation and hypertrophy, angiogenesis, endoplasmic reticulum stress, apoptosis, and senescence. Understanding the specific targets of ROS may guide the development of the next generation of ROS-modifying therapies to reduce morbidity and mortality associated with oxidative stress. © 2015 American Heart Association, Inc.

Regulation of signal transduction by reactive oxygen species in the cardiovascular system

PubMed Central

Brown, David I.; Griendling, Kathy K.

2015-01-01

Oxidative stress has long been implicated in cardiovascular disease, but more recently, the role of reactive oxygen species in normal physiological signaling has been elucidated. Signaling pathways modulated by reactive oxygen species (ROS) are complex and compartmentalized, and we are only beginning to identify the molecular modifications of specific targets. Here we review the current literature regarding ROS signaling in the cardiovascular system, focusing on the role of ROS in normal physiology and how dysregulation of signaling circuits contributes to cardiovascular diseases including atherosclerosis, ischemia-reperfusion injury, cardiomyopathy and heart failure. In particular, we consider how ROS modulate signaling pathways related to phenotypic modulation, migration and adhesion, contractility, proliferation and hypertrophy, angiogenesis, endoplasmic reticulum stress, apoptosis and senescence. Understanding the specific targets of ROS may guide the development of the next generation of ROS-modifying therapies to reduce morbidity and mortality associated with oxidative stress. PMID:25634975

Label-Free Neuroproteomics of the Hippocampal-Accumbal Circuit Reveals Deficits in Neurotransmitter and Neuropeptide Signaling in Mice Lacking Ethanol-Sensitive Adenosine Transporter.

PubMed

Oliveros, Alfredo; Starski, Phillip; Lindberg, Daniel; Choi, Sun; Heppelmann, Carrie J; Dasari, Surendra; Choi, Doo-Sup

2017-04-07

The neural circuit of the dorsal hippocampus (dHip) and nucleus accumbens (NAc) contributes to cue-induced learning and addictive behaviors, as demonstrated by the escalation of ethanol-seeking behaviors observed following deletion of the adenosine equilibrative nucleoside transporter 1 (ENT1 -/- ) in mice. Here we perform quantitative LC-MS/MS neuroproteomics in the dHip and NAc of ENT1 -/- mice. Using Ingenuity Pathway Analysis, we identified proteins associated with increased long-term potentiation, ARP2/3-mediated actin cytoskeleton signaling and protein expression patterns suggesting deficits in glutamate degradation, GABAergic signaling, as well as significant changes in bioenergetics and energy homeostasis (oxidative phosphorylation, TCA cycle, and glycolysis). These pathways are consistent with previously reported behavioral and biochemical phenotypes that typify mice lacking ENT1. Moreover, we validated decreased expression of the SNARE complex protein VAMP1 (synaptobrevin-1) in the dHip as well as decreased expression of pro-dynorphin (PDYN), neuroendocrine convertase (PCSK1), and Leu-Enkephalin (dynorphin-A) in the NAc. Taken together, our proteomic approach provides novel pathways indicating that ENT1-regulated signaling is essential for neurotransmitter release and neuropeptide processing, both of which underlie learning and reward-seeking behaviors.

Majority-voted logic fail-sense circuit

NASA Technical Reports Server (NTRS)

Mclyman, W. T.

1977-01-01

Fail-sense circuit has majority-voted logic component which receives three error voltage signals that are sensed at single point by three error amplifiers. If transistor shorts, only one signal is required to operate; if transistor opens, two signals are required.

Signal replication in a DNA nanostructure

NASA Astrophysics Data System (ADS)

Mendoza, Oscar; Houmadi, Said; Aimé, Jean-Pierre; Elezgaray, Juan

2017-01-01

Logic circuits based on DNA strand displacement reaction are the basic building blocks of future nanorobotic systems. The circuits tethered to DNA origami platforms present several advantages over solution-phase versions where couplings are always diffusion-limited. Here we consider a possible implementation of one of the basic operations needed in the design of these circuits, namely, signal replication. We show that with an appropriate preparation of the initial state, signal replication performs in a reproducible way. We also show the existence of side effects concomitant to the high effective concentrations in tethered circuits, such as slow leaky reactions and cross-activation.

Induction voidmeter

DOEpatents

Anderson, Thomas T.; Roop, Conard J.; Schmidt, Kenneth J.; Brewer, John

1986-01-01

An induction voidmeter for detecting voids in a conductive fluid may comprise: a four arm bridge circuit having two adjustable circuit elements connected as opposite arms of said bridge circuit, an input branch, and an output branch; two induction coils, bifilarly wound together, connected as the remaining two opposing arms of said bridge circuit and positioned such that the conductive fluid passes through said coils; applying an AC excitation signal to said input branch; and detecting the output signal generated in response to said excitation signal across said output branch. The induction coils may be located outside or inside a non-magnetic pipe containing the conductive fluid.

Engineering naturally occurring trans-acting non-coding RNAs to sense molecular signals

PubMed Central

Qi, Lei; Lucks, Julius B.; Liu, Chang C.; Mutalik, Vivek K.; Arkin, Adam P.

2012-01-01

Non-coding RNAs (ncRNAs) are versatile regulators in cellular networks. While most trans-acting ncRNAs possess well-defined mechanisms that can regulate transcription or translation, they generally lack the ability to directly sense cellular signals. In this work, we describe a set of design principles for fusing ncRNAs to RNA aptamers to engineer allosteric RNA fusion molecules that modulate the activity of ncRNAs in a ligand-inducible way in Escherichia coli. We apply these principles to ncRNA regulators that can regulate translation (IS10 ncRNA) and transcription (pT181 ncRNA), and demonstrate that our design strategy exhibits high modularity between the aptamer ligand-sensing motif and the ncRNA target-recognition motif, which allows us to reconfigure these two motifs to engineer orthogonally acting fusion molecules that respond to different ligands and regulate different targets in the same cell. Finally, we show that the same ncRNA fused with different sensing domains results in a sensory-level NOR gate that integrates multiple input signals to perform genetic logic. These ligand-sensing ncRNA regulators provide useful tools to modulate the activity of structurally related families of ncRNAs, and building upon the growing body of RNA synthetic biology, our ability to design aptamer–ncRNA fusion molecules offers new ways to engineer ligand-sensing regulatory circuits. PMID:22383579

Engineering self-contained DNA circuit for proximity recognition and localized signal amplification of target biomolecules

PubMed Central

Ang, Yan Shan; Yung, Lin-Yue Lanry

2014-01-01

Biomolecular interactions have important cellular implications, however, a simple method for the sensing of such proximal events is lacking in the current molecular toolbox. We designed a dynamic DNA circuit capable of recognizing targets in close proximity to initiate a pre-programmed signal transduction process resulting in localized signal amplification. The entire circuit was engineered to be self-contained, i.e. it can self-assemble onto individual target molecules autonomously and form localized signal with minimal cross-talk. α-thrombin was used as a model protein to evaluate the performance of the individual modules and the overall circuit for proximity interaction under physiologically relevant buffer condition. The circuit achieved good selectivity in presence of non-specific protein and interfering serum matrix and successfully detected for physiologically relevant α-thrombin concentration (50 nM–5 μM) in a single mixing step without any further washing. The formation of localized signal at the interaction site can be enhanced kinetically through the control of temperature and probe concentration. This work provides a basic general framework from which other circuit modules can be adapted for the sensing of other biomolecular or cellular interaction of interest. PMID:25056307

Design and implementation of JOM-3 Overhauser magnetometer analog circuit

NASA Astrophysics Data System (ADS)

Zhang, Xiao; Jiang, Xue; Zhao, Jianchang; Zhang, Shuang; Guo, Xin; Zhou, Tingting

2017-09-01

Overhauser magnetometer, a kind of static-magnetic measurement system based on the Overhauser effect, has been widely used in archaeological exploration, mineral resources exploration, oil and gas basin structure detection, prediction of engineering exploration environment, earthquakes and volcanic eruotions, object magnetic measurement and underground buried booty exploration. Overhauser magnetometer plays an important role in the application of magnetic field measurement for its characteristics of small size, low power consumption and high sensitivity. This paper researches the design and the application of the analog circuit of JOM-3 Overhauser magnetometer. First, the Larmor signal output by the probe is very weak. In order to obtain the signal with high signal to noise rstio(SNR), the design of pre-amplifier circuit is the key to improve the quality of the system signal. Second, in this paper, the effectual step which could improve the frequency characters of bandpass filter amplifier circuit were put forward, and theoretical analysis was made for it. Third, the shaping circuit shapes the amplified sine signal into a square wave signal which is suitable for detecting the rising edge. Fourth, this design elaborated the optimized choice of tuning circuit, so the measurement range of the magnetic field can be covered. Last, integrated analog circuit testing system was formed to detect waveform of each module. By calculating the standard deviation, the sensitivity of the improved Overhauser magnetometer is 0.047nT for Earth's magnetic field observation. Experimental results show that the new magnetometer is sensitive to earth field measurement.

Field Effect Transistor /FET/ circuit for variable gin amplifiers

NASA Technical Reports Server (NTRS)

Spaid, G. H.

1969-01-01

Amplifier circuit using two FETs combines improved input and output impedances with relatively large signal handling capability and an immunity from adverse effects of automatic gain control. Circuit has sources and drains in parallel plus a resistive divider for signal and bias to either of the gate terminals.

Trade Electricity. Signal Wiring--Level 1. Standardized Curriculum.

ERIC Educational Resources Information Center

New York City Board of Education, Brooklyn, NY. Office of Occupational and Career Education.

This curriculum guide consists of nine modules on signal wiring, one of the three divisions of the standardized trade electricity curriculum in high schools in New York City. The modules cover the following subjects: bells, double contact pushbuttons, annunciator circuits, open circuit burglar alarms, closed circuit burglar alarms, fire alarms,…

Pulse shaping circuit for active counting of superheated emulsion

NASA Astrophysics Data System (ADS)

Murai, Ikuo; Sawamura, Teruko

2005-08-01

A pulse shaping circuit for active counting of superheated emulsions is described. A piezoelectric transducer is used for sensing bubble formation acoustically and the acoustic signal is transformed to a shaping pulse for counting. The circuit has a short signal processing time in the order of 10 ms.

Single-Event Transient Testing of Low Dropout PNP Series Linear Voltage Regulators

NASA Technical Reports Server (NTRS)

Adell, Philippe; Allen, Gregory

2013-01-01

As demand for high-speed, on-board, digital-processing integrated circuits on spacecraft increases (field-programmable gate arrays and digital signal processors in particular), the need for the next generation point-of-load (POL) regulator becomes a prominent design issue. Shrinking process nodes have resulted in core rails dropping to values close to 1.0 V, drastically reducing margin to standard switching converters or regulators that power digital ICs. The goal of this task is to perform SET characterization of several commercial POL converters, and provide a discussion of the impact of these results to state-of-the-art digital processing IC through laser and heavy ion testing

Cassette for handling banknotes or the like

DOEpatents

Lundblad, Leif

1981-08-11

A cassette for banknotes and like valuable articles is provided with a displaceable lid (6) and locking means (10) for latching the lid of the cassette when the cassette is located outside a housing (25) in which it is intended to be placed. An operating means (8) is arranged to co-act with the locking means and with a latching element (15). The latching element is arranged to be released in dependence upon a pre-set program. A signal circuit is arranged to send a code signal to a detector circuit (23) when electrical contact elements on the cassette and the housing co-act with one another, which detector circuit, when the signal coincides with the signal program in the detector circuit, causes a signal to be sent for moving the latching means to a non-latching position.

Nulling Hall-Effect Current-Measuring Circuit

NASA Technical Reports Server (NTRS)

Sullender, Craig C.; Vazquez, Juan M.; Berru, Robert I.

1993-01-01

Circuit measures electrical current via combination of Hall-effect-sensing and magnetic-field-nulling techniques. Known current generated by feedback circuit adjusted until it causes cancellation or near cancellation of magnetic field produced in toroidal ferrite core by current measured. Remaining magnetic field measured by Hall-effect sensor. Circuit puts out analog signal and digital signal proportional to current measured. Accuracy of measurement does not depend on linearity of sensing components.

Wide-temperature integrated operational amplifier

NASA Technical Reports Server (NTRS)

Mojarradi, Mohammad (Inventor); Levanas, Greg (Inventor); Chen, Yuan (Inventor); Cozy, Raymond S. (Inventor); Greenwell, Robert (Inventor); Terry, Stephen (Inventor); Blalock, Benjamin J. (Inventor)

2009-01-01

The present invention relates to a reference current circuit. The reference circuit comprises a low-level current bias circuit, a voltage proportional-to-absolute temperature generator for creating a proportional-to-absolute temperature voltage (VPTAT), and a MOSFET-based constant-IC regulator circuit. The MOSFET-based constant-IC regulator circuit includes a constant-IC input and constant-IC output. The constant-IC input is electrically connected with the VPTAT generator such that the voltage proportional-to-absolute temperature is the input into the constant-IC regulator circuit. Thus the constant-IC output maintains the constant-IC ratio across any temperature range.

Acute engagement of Gq-mediated signaling in the bed nucleus of the stria terminalis induces anxiety-like behavior.

PubMed

Mazzone, C M; Pati, D; Michaelides, M; DiBerto, J; Fox, J H; Tipton, G; Anderson, C; Duffy, K; McKlveen, J M; Hardaway, J A; Magness, S T; Falls, W A; Hammack, S E; McElligott, Z A; Hurd, Y L; Kash, T L

2018-01-01

The bed nucleus of the stria terminalis (BNST) is a brain region important for regulating anxiety-related behavior in both humans and rodents. Here we used a chemogenetic strategy to investigate how engagement of G protein-coupled receptor (GPCR) signaling cascades in genetically defined GABAergic BNST neurons modulates anxiety-related behavior and downstream circuit function. We saw that stimulation of vesicular γ-aminobutyric acid (GABA) transporter (VGAT)-expressing BNST neurons using hM3Dq, but neither hM4Di nor rM3Ds designer receptors exclusively activated by a designer drug (DREADD), promotes anxiety-like behavior. Further, we identified that activation of hM3Dq receptors in BNST VGAT neurons can induce a long-term depression-like state of glutamatergic synaptic transmission, indicating DREADD-induced changes in synaptic plasticity. Further, we used DREADD-assisted metabolic mapping to profile brain-wide network activity following activation of G q -mediated signaling in BNST VGAT neurons and saw increased activity within ventral midbrain structures, including the ventral tegmental area and hindbrain structures such as the locus coeruleus and parabrachial nucleus. These results highlight that G q -mediated signaling in BNST VGAT neurons can drive downstream network activity that correlates with anxiety-like behavior and points to the importance of identifying endogenous GPCRs within genetically defined cell populations. We next used a microfluidics approach to profile the receptorome of single BNST VGAT neurons. This approach yielded multiple G q -coupled receptors that are associated with anxiety-like behavior and several potential novel candidates for regulation of anxiety-like behavior. From this, we identified that stimulation of the G q -coupled receptor 5-HT 2C R in the BNST is sufficient to elevate anxiety-like behavior in an acoustic startle task. Together, these results provide a novel profile of receptors within genetically defined BNST VGAT neurons that may serve as therapeutic targets for regulating anxiety states and provide a blueprint for examining how G-protein-mediated signaling in a genetically defined cell type can be used to assess behavior and brain-wide circuit function.

Corticosterone Signaling and a Lateral Habenula-Ventral Tegmental Area Circuit Modulate Compulsive Self-Injurious Behavior in a Rat Model.

PubMed

Guo, Yujie; Tang, Xun; Zhang, Jichuan; Jin, Sen; Li, Jinnan; Ding, Lufeng; Zhang, Keming; Yang, Chaoyu; Zhou, Hua; He, Xiaobin; Xu, Fuqiang; Bi, Guo-Qiang; Xu, Lin; Lau, Pak-Ming

2018-06-06

Self-injurious behavior (SIB) is commonly observed in patients with neuropsychiatric disorders, as well as in nonclinical populations with stress-related mental-health problems. However, the exact circuitry mechanisms underlying SIB have remained poorly understood. Here, with bilateral injection of muscimol into the entopeduncular nucleus (EP), we established a rat model of SIB. Following the muscimol injection, the male rats exhibited in a dose-dependent manner stereotypic self-biting behavior that lasted for hours and often resulted in wounds of various severities. The SIB was associated with an elevated level of serum corticosterone and could be exacerbated by enhancing the corticosterone signaling and, conversely, alleviated by inhibiting the corticosterone signaling. Activity mapping using c-fos immunostaining, combined with connectivity mapping using herpes simplex virus-based anterograde tracing from the EP and pseudorabies virus-based retrograde tracing from the masseter muscle, revealed the potential involvement of many brain areas in SIB. In particular, the lateral habenula (LHb) and the ventral tegmental area (VTA), the two connected brain areas involved in stress response and reward processing, showed a significant increase in neuronal activation during SIB. Furthermore, suppressing the LHb activity or modulating the GABAergic transmission in the VTA could significantly reduce the occurrence of SIB. These results demonstrate the importance of stress hormone signaling and the LHb-VTA circuit in modulating SIB resulting from EP malfunction, and suggest potential targets for therapeutic intervention of SIB and related disorders. SIGNIFICANCE STATEMENT Self-injurious behavior (SIB) occurs in ∼4% of the general population, with substantially higher occurrence among adolescents and patients of neuropsychiatric disorders. Stress has been linked to the occurrence of SIB, yet the underlying mechanisms have remained unclear. Using a rat model of SIB induced by disruption of activity in the entopeduncular nucleus (EP), we found that the behavior is regulated by stress and linked to corticosterone signaling. Viral tracing and c-fos immunostaining revealed the involvement of various subcortical areas, especially the EP-lateral habenula (LHb)-ventral tegmental area (VTA) circuit, in SIB. Furthermore, regulating activity in the LHb or the VTA alleviates SIB. These results may have implications in the development of new strategies for treating SIB. Copyright © 2018 the authors 0270-6474/18/385252-16$15.00/0.

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.

System and Method for Multi-Wavelength Optical Signal Detection

NASA Technical Reports Server (NTRS)

McGlone, Thomas D. (Inventor)

2017-01-01

The system and method for multi-wavelength optical signal detection enables the detection of optical signal levels significantly below those processed at the discrete circuit level by the use of mixed-signal processing methods implemented with integrated circuit technologies. The present invention is configured to detect and process small signals, which enables the reduction of the optical power required to stimulate detection networks, and lowers the required laser power to make specific measurements. The present invention provides an adaptation of active pixel networks combined with mixed-signal processing methods to provide an integer representation of the received signal as an output. The present invention also provides multi-wavelength laser detection circuits for use in various systems, such as a differential absorption light detection and ranging system.

Feedback loop compensates for rectifier nonlinearity

NASA Technical Reports Server (NTRS)

1966-01-01

Signal processing circuit with two negative feedback loops rectifies two sinusoidal signals which are 180 degrees out of phase and produces a single full-wave rectified output signal. Each feedback loop incorporates a feedback rectifier to compensate for the nonlinearity of the circuit.

Activation of YUCCA5 by the Transcription Factor TCP4 Integrates Developmental and Environmental Signals to Promote Hypocotyl Elongation in Arabidopsis.

PubMed

Challa, Krishna Reddy; Aggarwal, Pooja; Nath, Utpal

2016-09-05

Cell expansion is an essential process in plant morphogenesis and is regulated by the coordinated action of environmental stimuli and endogenous factors, such as the phytohormones auxin and brassinosteroid. Although the biosynthetic pathways that generate these hormones and their downstream signaling mechanisms have been extensively studied, the upstream transcriptional network that modulates their levels and connects their action to cell morphogenesis is less clear. Here we show that the miR319-regulated TCP (TEOSINTE BRANCHED 1, CYCLODEA, PROLIFERATING CELL FACTORS) transcription factors, notably TCP4, directly activate YUCCA5 transcription and integrate the auxin response to a brassinosteroid-dependent molecular circuit that promotes cell elongation in Arabidopsis hypocotyls. Further, TCP4 modulates the common transcriptional network downstream to auxin-BR signaling, which is also triggered by environmental cues, such as light, to promote cell expansion. Our study links TCP function with the hormone response during cell morphogenesis and shows that developmental and environmental signals converge on a common transcriptional network to promote cell elongation. {copyright, serif} 2016 American Society of Plant Biologists. All rights reserved.

Crossed SMPS MOSFET-based protection circuit for high frequency ultrasound transceivers and transducers

PubMed Central

2014-01-01

Background The ultrasonic transducer is one of the core components of ultrasound systems, and the transducer’s sensitivity is significantly related the loss of electronic components such as the transmitter, receiver, and protection circuit. In an ultrasonic device, protection circuits are commonly used to isolate the electrical noise between an ultrasound transmitter and transducer and to minimize unwanted discharged pulses in order to protect the ultrasound receiver. However, the performance of the protection circuit and transceiver obviously degrade as the operating frequency or voltage increases. We therefore developed a crossed SMPS (Switching Mode Power Supply) MOSFET-based protection circuit in order to maximize the sensitivity of high frequency transducers in ultrasound systems. The high frequency pulse signals need to trigger the transducer, and high frequency pulse signals must be received by the transducer. We therefore selected the SMPS MOSFET, which is the main component of the protection circuit, to minimize the loss in high frequency operation. The crossed configuration of the protection circuit can drive balanced bipolar high voltage signals from the pulser and transfer the balanced low voltage echo signals from the transducer. Methods The equivalent circuit models of the SMPS MOSFET-based protection circuit are shown in order to select the proper device components. The schematic diagram and operation mechanism of the protection circuit is provided to show how the protection circuit is constructed. The P-Spice circuit simulation was also performed in order to estimate the performance of the crossed MOSFET-based protection circuit. Results We compared the performance of our crossed SMPS MOSFET-based protection circuit with a commercial diode-based protection circuit. At 60 MHz, our expander and limiter circuits have lower insertion loss than the commercial diode-based circuits. The pulse-echo test is typical method to evaluate the sensitivity of ultrasonic transducers. Therefore, we performed a pulse-echo test using a single element transducer in order to utilize the crossed SMPS MOSFET-based protection circuit in an ultrasound system. Conclusions The SMPS-based protection circuit could be a viable alternative that provides better sensitivity, especially for high frequency ultrasound applications. PMID:24924595

Crossed SMPS MOSFET-based protection circuit for high frequency ultrasound transceivers and transducers.

PubMed

Choi, Hojong; Shung, K Kirk

2014-06-12

The ultrasonic transducer is one of the core components of ultrasound systems, and the transducer's sensitivity is significantly related the loss of electronic components such as the transmitter, receiver, and protection circuit. In an ultrasonic device, protection circuits are commonly used to isolate the electrical noise between an ultrasound transmitter and transducer and to minimize unwanted discharged pulses in order to protect the ultrasound receiver. However, the performance of the protection circuit and transceiver obviously degrade as the operating frequency or voltage increases. We therefore developed a crossed SMPS (Switching Mode Power Supply) MOSFET-based protection circuit in order to maximize the sensitivity of high frequency transducers in ultrasound systems.The high frequency pulse signals need to trigger the transducer, and high frequency pulse signals must be received by the transducer. We therefore selected the SMPS MOSFET, which is the main component of the protection circuit, to minimize the loss in high frequency operation. The crossed configuration of the protection circuit can drive balanced bipolar high voltage signals from the pulser and transfer the balanced low voltage echo signals from the transducer. The equivalent circuit models of the SMPS MOSFET-based protection circuit are shown in order to select the proper device components. The schematic diagram and operation mechanism of the protection circuit is provided to show how the protection circuit is constructed. The P-Spice circuit simulation was also performed in order to estimate the performance of the crossed MOSFET-based protection circuit. We compared the performance of our crossed SMPS MOSFET-based protection circuit with a commercial diode-based protection circuit. At 60 MHz, our expander and limiter circuits have lower insertion loss than the commercial diode-based circuits. The pulse-echo test is typical method to evaluate the sensitivity of ultrasonic transducers. Therefore, we performed a pulse-echo test using a single element transducer in order to utilize the crossed SMPS MOSFET-based protection circuit in an ultrasound system. The SMPS-based protection circuit could be a viable alternative that provides better sensitivity, especially for high frequency ultrasound applications.

A PDF/NPF neuropeptide signaling circuitry of male Drosophila melanogaster controls rival-induced prolonged mating.

PubMed

Kim, Woo Jae; Jan, Lily Yeh; Jan, Yuh Nung

2013-12-04

A primary function of males for many species involves mating with females for reproduction. Drosophila melanogaster males respond to the presence of other males by prolonging mating duration to increase the chance of passing on their genes. To understand the basis of such complex behaviors, we examine the genetic network and neural circuits that regulate rival-induced Longer-Mating-Duration (LMD). Here, we identify a small subset of clock neurons in the male brain that regulate LMD via neuropeptide signaling. LMD requires the function of pigment-dispersing factor (PDF) in four s-LNv neurons and its receptor PDFR in two LNd neurons per hemisphere, as well as the function of neuropeptide F (NPF) in two neurons within the sexually dimorphic LNd region and its receptor NPFR1 in four s-LNv neurons per hemisphere. Moreover, rival exposure modifies the neuronal activities of a subset of clock neurons involved in neuropeptide signaling for LMD. Copyright © 2013 Elsevier Inc. All rights reserved.

A PDF/NPF neuropeptide signaling circuitry of male Drosophila melanogaster controls rival-induced prolonged mating

PubMed Central

Kim, Woo Jae; Jan, Lily Yeh; Jan, Yuh Nung

2013-01-01

SUMMARY A primary function of males for many species involves mating with females for reproduction. Drosophila melanogaster males respond to the presence of other males by prolonging mating duration to increase the chance of passing on their genes. To understand the basis of such complex behaviors, we examine the genetic network and neural circuits that regulate rival-induced longer mating duration (LMD). Here we identify a small subset of clock neurons in the male brain that regulate LMD via neuropeptide signaling. LMD requires the function of pigment-dispersing factor (PDF) in four s-LNv neurons and its receptor PDFR in two LNd neurons per hemisphere, as well as the function of neuropeptide F (NPF) in two neurons within the sexually dimorphic LNd region and its receptor NPFR1 in four s-LNv neurons per hemisphere. Moreover, rival exposure modifies the neuronal activities of a subset of clock neurons involved in neuropeptide signaling for LMD. PMID:24314729

Integral control of plant gravitropism through the interplay of hormone signaling and gene regulation.

PubMed

Rodrigo, Guillermo; Jaramillo, Alfonso; Blázquez, Miguel A

2011-08-17

The interplay between hormone signaling and gene regulatory networks is instrumental in promoting the development of living organisms. In particular, plants have evolved mechanisms to sense gravity and orient themselves accordingly. Here, we present a mathematical model that reproduces plant gravitropic responses based on known molecular genetic interactions for auxin signaling coupled with a physical description of plant reorientation. The model allows one to analyze the spatiotemporal dynamics of the system, triggered by an auxin gradient that induces differential growth of the plant with respect to the gravity vector. Our model predicts two important features with strong biological implications: 1), robustness of the regulatory circuit as a consequence of integral control; and 2), a higher degree of plasticity generated by the molecular interplay between two classes of hormones. Our model also predicts the ability of gibberellins to modulate the tropic response and supports the integration of the hormonal role at the level of gene regulation. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Regulation of branching dynamics by axon-intrinsic asymmetries in Tyrosine Kinase Receptor signaling

PubMed Central

Zschätzsch, Marlen; Oliva, Carlos; Langen, Marion; De Geest, Natalie; Özel, Mehmet Neset; Williamson, W Ryan; Lemon, William C; Soldano, Alessia; Munck, Sebastian; Hiesinger, P Robin; Sanchez-Soriano, Natalia; Hassan, Bassem A

2014-01-01

Axonal branching allows a neuron to connect to several targets, increasing neuronal circuit complexity. While axonal branching is well described, the mechanisms that control it remain largely unknown. We find that in the Drosophila CNS branches develop through a process of excessive growth followed by pruning. In vivo high-resolution live imaging of developing brains as well as loss and gain of function experiments show that activation of Epidermal Growth Factor Receptor (EGFR) is necessary for branch dynamics and the final branching pattern. Live imaging also reveals that intrinsic asymmetry in EGFR localization regulates the balance between dynamic and static filopodia. Elimination of signaling asymmetry by either loss or gain of EGFR function results in reduced dynamics leading to excessive branch formation. In summary, we propose that the dynamic process of axon branch development is mediated by differential local distribution of signaling receptors. DOI: http://dx.doi.org/10.7554/eLife.01699.001 PMID:24755286

Cdk5 Is Required for Memory Function and Hippocampal Plasticity via the cAMP Signaling Pathway

PubMed Central

Gao, Jun; Joseph, Nadine; Xie, Zhigang; Zhou, Ying; Durak, Omer; Zhang, Lei; Zhu, J. Julius; Clauser, Karl R.; Carr, Steven A.; Tsai, Li-Huei

2011-01-01

Memory formation is modulated by pre- and post-synaptic signaling events in neurons. The neuronal protein kinase Cyclin-Dependent Kinase 5 (Cdk5) phosphorylates a variety of synaptic substrates and is implicated in memory formation. It has also been shown to play a role in homeostatic regulation of synaptic plasticity in cultured neurons. Surprisingly, we found that Cdk5 loss of function in hippocampal circuits results in severe impairments in memory formation and retrieval. Moreover, Cdk5 loss of function in the hippocampus disrupts cAMP signaling due to an aberrant increase in phosphodiesterase (PDE) proteins. Dysregulation of cAMP is associated with defective CREB phosphorylation and disrupted composition of synaptic proteins in Cdk5-deficient mice. Rolipram, a PDE4 inhibitor that prevents cAMP depletion, restores synaptic plasticity and memory formation in Cdk5-deficient mice. Collectively, our results demonstrate a critical role for Cdk5 in the regulation of cAMP-mediated hippocampal functions essential for synaptic plasticity and memory formation. PMID:21984943

Vehicle security apparatus and method

DOEpatents

Veligdan, James T.

1996-02-13

A vehicle security apparatus for use in a motor vehicle, the apparatus comprising an optical key, a receptacle, a receiver and at least one optical fiber. The optical key has a transmitter having at least one first preprogrammed coded signal stored in a first electric circuit. The receptacle receives the optical key and at least one transmittable coded optical signal from the transmitter corresponding to the at least one preprogrammed coded signal stored in the first electric circuit. The receiver compares the at least one transmittable coded optical signal to at least one second preprogrammed coded signal stored in a second electric circuit and the receiver is adapted to trigger switching effects for at least one of enabling starting the motor vehicle and starting the motor vehicle upon determination that the at least one transmittable coded optical signal corresponds to the at least one second preprogrammed signal in the second electric circuit. The at least one optical fiber is operatively connected between the receptacle and the receiver for carrying the optical signal from the receptacle to the receiver. Also disclosed is a method for permitting only authorized use of a motor vehicle.

FlpStop, a tool for conditional gene control in Drosophila

PubMed Central

Fisher, Yvette E; Yang, Helen H; Isaacman-Beck, Jesse; Xie, Marjorie; Gohl, Daryl M; Clandinin, Thomas R

2017-01-01

Manipulating gene function cell type-specifically is a common experimental goal in Drosophila research and has been central to studies of neural development, circuit computation, and behavior. However, current cell type-specific gene disruption techniques in flies often reduce gene activity incompletely or rely on cell division. Here we describe FlpStop, a generalizable tool for conditional gene disruption and rescue in post-mitotic cells. In proof-of-principle experiments, we manipulated apterous, a regulator of wing development. Next, we produced conditional null alleles of Glutamic acid decarboxylase 1 (Gad1) and Resistant to dieldrin (Rdl), genes vital for GABAergic neurotransmission, as well as cacophony (cac) and paralytic (para), voltage-gated ion channels central to neuronal excitability. To demonstrate the utility of this approach, we manipulated cac in a specific visual interneuron type and discovered differential regulation of calcium signals across subcellular compartments. Thus, FlpStop will facilitate investigations into the interactions between genes, circuits, and computation. DOI: http://dx.doi.org/10.7554/eLife.22279.001 PMID:28211790

Circuit protects regulated power supply against overload current

NASA Technical Reports Server (NTRS)

Airth, H. B.

1966-01-01

Sensing circuit in which a tunnel diode controls a series regulator transistor protects a low voltage transistorized dc regulator from damage by excessive load currents. When a fault occurs, the faulty circuit is limited to a preset percentage of the current when limiting first occurs.

Diode-quad bridge circuit means

NASA Technical Reports Server (NTRS)

Harrison, D. R.; Dimeff, J. (Inventor)

1975-01-01

Diode-quad bridge circuit means is described for use as a transducer circuit or as a discriminator circuit. It includes: (1) a diode bridge having first, second, third, and fourth bridge terminals consecutively coupled together by four diodes polarized in circulating relationship; (2) a first impedance connected between the second bridge terminal and a circuit ground; (3) a second impedance connected between the fourth bridge terminal and the circuit ground; (4) a signal source having a first source terminal capacitively coupled to the first and third bridge terminals, and a second source terminal connected to the circuit ground; and (5) an output terminal coupled to the first bridge terminal and at which an output signal may be taken.

AgRP to Kiss1 neuron signaling links nutritional state and fertility

PubMed Central

Padilla, Stephanie L.; Qiu, Jian; Nestor, Casey C; Zhang, Chunguang; Smith, Arik W.; Whiddon, Benjamin B.; Rønnekleiv, Oline K.; Kelly, Martin J.; Palmiter, Richard D.

2017-01-01

Mammalian reproductive function depends upon a neuroendocrine circuit that evokes the pulsatile release of gonadotropin hormones (luteinizing hormone and follicle-stimulating hormone) from the pituitary. This reproductive circuit is sensitive to metabolic perturbations. When challenged with starvation, insufficient energy reserves attenuate gonadotropin release, leading to infertility. The reproductive neuroendocrine circuit is well established, composed of two populations of kisspeptin-expressing neurons (located in the anteroventral periventricular hypothalamus, Kiss1AVPV, and arcuate hypothalamus, Kiss1ARH), which drive the pulsatile activity of gonadotropin-releasing hormone (GnRH) neurons. The reproductive axis is primarily regulated by gonadal steroid and circadian cues, but the starvation-sensitive input that inhibits this circuit during negative energy balance remains controversial. Agouti-related peptide (AgRP)-expressing neurons are activated during starvation and have been implicated in leptin-associated infertility. To test whether these neurons relay information to the reproductive circuit, we used AgRP-neuron ablation and optogenetics to explore connectivity in acute slice preparations. Stimulation of AgRP fibers revealed direct, inhibitory synaptic connections with Kiss1ARH and Kiss1AVPV neurons. In agreement with this finding, Kiss1ARH neurons received less presynaptic inhibition in the absence of AgRP neurons (neonatal toxin-induced ablation). To determine whether enhancing the activity of AgRP neurons is sufficient to attenuate fertility in vivo, we artificially activated them over a sustained period and monitored fertility. Chemogenetic activation with clozapine N-oxide resulted in delayed estrous cycles and decreased fertility. These findings are consistent with the idea that, during metabolic deficiency, AgRP signaling contributes to infertility by inhibiting Kiss1 neurons. PMID:28196880

Low-noise pulse conditioner

DOEpatents

Bird, David A.

1983-01-01

A low-noise pulse conditioner is provided for driving electronic digital processing circuitry directly from differentially induced input pulses. The circuit uses a unique differential-to-peak detector circuit to generate a dynamic reference signal proportional to the input peak voltage. The input pulses are compared with the reference signal in an input network which operates in full differential mode with only a passive input filter. This reduces the introduction of circuit-induced noise, or jitter, generated in ground referenced input elements normally used in pulse conditioning circuits, especially speed transducer processing circuits.

7 CFR 1703.102 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... information, and is normally found on the terminal of a circuit and on the premises of the end user. Distance... telecommunications equipment at the end of a circuit or path of a signal, including but not limited to facilities..., the purpose of which is to accomplish the goal for which the circuit or signal was established...

7 CFR 1703.102 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... information, and is normally found on the terminal of a circuit and on the premises of the end user. Distance... telecommunications equipment at the end of a circuit or path of a signal, including but not limited to facilities..., the purpose of which is to accomplish the goal for which the circuit or signal was established...

7 CFR 1703.102 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... information, and is normally found on the terminal of a circuit and on the premises of the end user. Distance... telecommunications equipment at the end of a circuit or path of a signal, including but not limited to facilities..., the purpose of which is to accomplish the goal for which the circuit or signal was established...

Circuit for echo and noise suppression of accoustic signals transmitted through a drill string

DOEpatents

Drumheller, Douglas S.; Scott, Douglas D.

1993-01-01

An electronic circuit for digitally processing analog electrical signals produced by at least one acoustic transducer is presented. In a preferred embodiment of the present invention, a novel digital time delay circuit is utilized which employs an array of First-in-First-out (FiFo) microchips. Also, a bandpass filter is used at the input to this circuit for isolating drill string noise and eliminating high frequency output.

Data acquisition channel apparatus

NASA Astrophysics Data System (ADS)

Higgins, C. H.; Skipper, J. D.

1985-10-01

Dicussed is a hybrid integrated circuit data acquisition channel apparatus employing an operational amplifier fed by a low current differential bipolar transistor preamplifier having separate feedback gain and signal gain determining elements and providing an amplified signal output to a sample and hold and analog-to-digital converter circuits. The disclosed apparatus operates with low energy and small space requirements and is capable of operations without the sample and hold circuit where the nature of the applied input signal permits.

Regulated Capacitor Charging Circuit Using a High Reactance Transformer

DTIC Science & Technology

1999-06-01

REGULATED CAPACITOR CHARGING CIRCUIT USING A HIGH REACTANCE TRANSFORMER1 Diana L. Loree and James P. O’Loughlin Air Force Research Laboratory...Directed Energy Directorate Kirtland Air Force Base, NM 87117-5776 Abstract A high reactance transformer circuit is used to provide for the compact...simple, economic and reliable charging of a capacitor energy store to a predetermined and regulated voltage. The circuit can be operated from a

Origins of heterogeneity in Streptococcus mutans competence: interpreting an environment-sensitive signaling pathway

NASA Astrophysics Data System (ADS)

Hagen, Stephen J.; Son, Minjun

2017-02-01

Bacterial pathogens rely on chemical signaling and environmental cues to regulate disease-causing behavior in complex microenvironments. The human pathogen Streptococcus mutans employs a particularly complex signaling and sensing scheme to regulate genetic competence and other virulence behaviors in the oral biofilms it inhabits. Individual S. mutans cells make the decision to enter the competent state by integrating chemical and physical cues received from their microenvironment along with endogenously produced peptide signals. Studies at the single-cell level, using microfluidics to control the extracellular environment, provide physical insight into how the cells process these inputs to generate complex and often heterogeneous outputs. Fine changes in environmental stimuli can dramatically alter the behavior of the competence circuit. Small shifts in pH can switch the quorum sensing response on or off, while peptide-rich media appear to switch the output from a unimodal to a bimodal behavior. Therefore, depending on environmental cues, the quorum sensing circuitry can either synchronize virulence across the population, or initiate and amplify heterogeneity in that behavior. Much of this complex behavior can be understood within the framework of a quorum sensing system that can operate both as an intercellular signaling mechanism and intracellularly as a noisy bimodal switch.

Electronic filters, signal conversion apparatus, hearing aids and methods

NASA Technical Reports Server (NTRS)

Morley, Jr., Robert E. (Inventor); Engebretson, A. Maynard (Inventor); Engel, George L. (Inventor); Sullivan, Thomas J. (Inventor)

1994-01-01

An electronic filter for filtering an electrical signal. Signal processing circuitry therein includes a logarithmic filter having a series of filter stages with inputs and outputs in cascade and respective circuits associated with the filter stages for storing electrical representations of filter parameters. The filter stages include circuits for respectively adding the electrical representations of the filter parameters to the electrical signal to be filtered thereby producing a set of filter sum signals. At least one of the filter stages includes circuitry for producing a filter signal in substantially logarithmic form at its output by combining a filter sum signal for that filter stage with a signal from an output of another filter stage. The signal processing circuitry produces an intermediate output signal, and a multiplexer connected to the signal processing circuit multiplexes the intermediate output signal with the electrical signal to be filtered so that the logarithmic filter operates as both a logarithmic prefilter and a logarithmic postfilter. Other electronic filters, signal conversion apparatus, electroacoustic systems, hearing aids and methods are also disclosed.

Endothelial cells dynamically compete for the tip cell position during angiogenic sprouting.

PubMed

Jakobsson, Lars; Franco, Claudio A; Bentley, Katie; Collins, Russell T; Ponsioen, Bas; Aspalter, Irene M; Rosewell, Ian; Busse, Marta; Thurston, Gavin; Medvinsky, Alexander; Schulte-Merker, Stefan; Gerhardt, Holger

2010-10-01

Sprouting angiogenesis requires the coordinated behaviour of endothelial cells, regulated by Notch and vascular endothelial growth factor receptor (VEGFR) signalling. Here, we use computational modelling and genetic mosaic sprouting assays in vitro and in vivo to investigate the regulation and dynamics of endothelial cells during tip cell selection. We find that endothelial cells compete for the tip cell position through relative levels of Vegfr1 and Vegfr2, demonstrating a biological role for differential Vegfr regulation in individual endothelial cells. Differential Vegfr levels affect tip selection only in the presence of a functional Notch system by modulating the expression of the ligand Dll4. Time-lapse microscopy imaging of mosaic sprouts identifies dynamic position shuffling of tip and stalk cells in vitro and in vivo, indicating that the VEGFR-Dll4-Notch signalling circuit is constantly re-evaluated as cells meet new neighbours. The regular exchange of the leading tip cell raises novel implications for the concept of guided angiogenic sprouting.

Investigating neuronal function with optically controllable proteins

PubMed Central

Zhou, Xin X.; Pan, Michael; Lin, Michael Z.

2015-01-01

In the nervous system, protein activities are highly regulated in space and time. This regulation allows for fine modulation of neuronal structure and function during development and adaptive responses. For example, neurite extension and synaptogenesis both involve localized and transient activation of cytoskeletal and signaling proteins, allowing changes in microarchitecture to occur rapidly and in a localized manner. To investigate the role of specific protein regulation events in these processes, methods to optically control the activity of specific proteins have been developed. In this review, we focus on how photosensory domains enable optical control over protein activity and have been used in neuroscience applications. These tools have demonstrated versatility in controlling various proteins and thereby cellular functions, and possess enormous potential for future applications in nervous systems. Just as optogenetic control of neuronal firing using opsins has changed how we investigate the function of cellular circuits in vivo, optical control may yet yield another revolution in how we study the circuitry of intracellular signaling in the brain. PMID:26257603

ELECTRONIC MULTIPLIER CIRCUIT

DOEpatents

Thomas, R.E.

1959-08-25

An electronic multiplier circuit is described in which an output voltage having an amplitude proportional to the product or quotient of the input signals is accomplished in a novel manner which facilitates simplicity of circuit construction and a high degree of accuracy in accomplishing the multiplying and dividing function. The circuit broadly comprises a multiplier tube in which the plate current is proportional to the voltage applied to a first control grid multiplied by the difference between voltage applied to a second control grid and the voltage applied to the first control grid. Means are provided to apply a first signal to be multiplied to the first control grid together with means for applying the sum of the first signal to be multiplied and a second signal to be multiplied to the second control grid whereby the plate current of the multiplier tube is proportional to the product of the first and second signals to be multiplied.

NbN A/D Conversion of IR Focal Plane Sensor Signal at 10 K

NASA Technical Reports Server (NTRS)

Eaton, L.; Durand, D.; Sandell, R.; Spargo, J.; Krabach, T.

1994-01-01

We are implementing a 12 bit SFQ counting ADC with parallel-to-serial readout using our established 10 K NbN capability. This circuit provides a key element of the analog signal processor (ASP) used in large infrared focal plane arrays. The circuit processes the signal data stream from a Si:As BIB detector array. A 10 mega samples per second (MSPS) pixel data stream flows from the chip at a 120 megabit bit rate in a format that is compatible with other superconductive time dependent processor (TDP) circuits being developed. We will discuss our planned ASP demonstration, the circuit design, and test results.

Genetic Circuits that Govern Bisexual and Unisexual Reproduction in Cryptococcus neoformans

PubMed Central

Feretzaki, Marianna; Heitman, Joseph

2013-01-01

Cryptococcus neoformans is a human fungal pathogen with a defined sexual cycle. Nutrient-limiting conditions and pheromones induce a dimorphic transition from unicellular yeast to multicellular hyphae and the production of infectious spores. Sexual reproduction involves cells of either opposite (bisexual) or one (unisexual) mating type. Bisexual and unisexual reproduction are governed by shared components of the conserved pheromone-sensing Cpk1 MAPK signal transduction cascade and by Mat2, the major transcriptional regulator of the pathway. However, the downstream targets of the pathway are largely unknown, and homology-based approaches have failed to yield downstream transcriptional regulators or other targets. In this study, we applied insertional mutagenesis via Agrobacterium tumefaciens transkingdom DNA delivery to identify mutants with unisexual reproduction defects. In addition to elements known to be involved in sexual development (Crg1, Ste7, Mat2, and Znf2), three key regulators of sexual development were identified by our screen: Znf3, Spo11, and Ubc5. Spo11 and Ubc5 promote sporulation during both bisexual and unisexual reproduction. Genetic and phenotypic analyses provide further evidence implicating both genes in the regulation of meiosis. Phenotypic analysis of sexual development showed that Znf3 is required for hyphal development during unisexual reproduction and also plays a central role during bisexual reproduction. Znf3 promotes cell fusion and pheromone production through a pathway parallel to and independent of the pheromone signaling cascade. Surprisingly, Znf3 participates in transposon silencing during unisexual reproduction and may serve as a link between RNAi silencing and sexual development. Our studies illustrate the power of unbiased genetic screens to reveal both novel and conserved circuits that operate sexual reproduction. PMID:23966871

Genetic circuits that govern bisexual and unisexual reproduction in Cryptococcus neoformans.

PubMed

Feretzaki, Marianna; Heitman, Joseph

2013-01-01

Cryptococcus neoformans is a human fungal pathogen with a defined sexual cycle. Nutrient-limiting conditions and pheromones induce a dimorphic transition from unicellular yeast to multicellular hyphae and the production of infectious spores. Sexual reproduction involves cells of either opposite (bisexual) or one (unisexual) mating type. Bisexual and unisexual reproduction are governed by shared components of the conserved pheromone-sensing Cpk1 MAPK signal transduction cascade and by Mat2, the major transcriptional regulator of the pathway. However, the downstream targets of the pathway are largely unknown, and homology-based approaches have failed to yield downstream transcriptional regulators or other targets. In this study, we applied insertional mutagenesis via Agrobacterium tumefaciens transkingdom DNA delivery to identify mutants with unisexual reproduction defects. In addition to elements known to be involved in sexual development (Crg1, Ste7, Mat2, and Znf2), three key regulators of sexual development were identified by our screen: Znf3, Spo11, and Ubc5. Spo11 and Ubc5 promote sporulation during both bisexual and unisexual reproduction. Genetic and phenotypic analyses provide further evidence implicating both genes in the regulation of meiosis. Phenotypic analysis of sexual development showed that Znf3 is required for hyphal development during unisexual reproduction and also plays a central role during bisexual reproduction. Znf3 promotes cell fusion and pheromone production through a pathway parallel to and independent of the pheromone signaling cascade. Surprisingly, Znf3 participates in transposon silencing during unisexual reproduction and may serve as a link between RNAi silencing and sexual development. Our studies illustrate the power of unbiased genetic screens to reveal both novel and conserved circuits that operate sexual reproduction.

Hunger and Satiety Signaling: Modeling Two Hypothalamomedullary Pathways for Energy Homeostasis.

PubMed

Nakamura, Kazuhiro; Nakamura, Yoshiko

2018-06-04

The recent discovery of the medullary circuit driving "hunger responses" - reduced thermogenesis and promoted feeding - has greatly expanded our knowledge on the central neural networks for energy homeostasis. However, how hypothalamic hunger and satiety signals generated under fasted and fed conditions, respectively, control the medullary autonomic and somatic motor mechanisms remains unknown. Here, in reviewing this field, we propose two hypothalamomedullary neural pathways for hunger and satiety signaling. To trigger hunger signaling, neuropeptide Y activates a group of neurons in the paraventricular hypothalamic nucleus (PVH), which then stimulate an excitatory pathway to the medullary circuit to drive the hunger responses. In contrast, melanocortin-mediated satiety signaling activates a distinct group of PVH neurons, which then stimulate a putatively inhibitory pathway to the medullary circuit to counteract the hunger signaling. The medullary circuit likely contains inhibitory and excitatory premotor neurons whose alternate phasic activation generates the coordinated masticatory motor rhythms to promote feeding. © 2018 The Authors. BioEssays Published by WILEY Periodicals, Inc.

ZERO SUPPRESSION FOR RECORDERS

DOEpatents

Fort, W.G.S.

1958-12-30

A zero-suppression circuit for self-balancing recorder instruments is presented. The essential elements of the circuit include a converter-amplifier having two inputs, one for a reference voltage and the other for the signal voltage under analysis, and a servomotor with two control windings, one coupled to the a-c output of the converter-amplifier and the other receiving a reference input. Each input circuit to the converter-amplifier has a variable potentiometer and the sliders of the potentiometer are ganged together for movement by the servoinotor. The particular noveity of the circuit resides in the selection of resistance values for the potentiometer and a resistor in series with the potentiometer of the signal circuit to ensure the full value of signal voltage variation is impressed on a recorder mechanism driven by servomotor.

A System for Controlling the Oxygen Content of a Gas Produced by Combustion

NASA Technical Reports Server (NTRS)

Singh, J. J.; Davis, W. T.; Puster, R. L. (Inventor)

1984-01-01

A mixture of air, CH4 and OH(2) is burned in a combustion chamber to produce a product gas in the test section. The OH(2) content of the product gas is compared with the OH(2) content of reference air in an OH(2) sensor. If there is a difference an error signal is produced at the output of a control circuit which by the means of a solenoid valve, regulates the flow of OH(2) into the combustion chamber to make the error signal zero. The product gas in the test section has the same oxygen content as air.

Compact Feed Circuit with Quarter Wavelength Transmission Line Matrix Controlling Beams in Three Directions Including Boresight

NASA Astrophysics Data System (ADS)

Tsuji, Masatoshi

A compact feed circuit with a λ/4 transmission line matrix circuit for use in array antennas to control beams in three directions, including boresight, is presented. The feed circuit antenna is composed of five switches and λ/4 transmission lines, and the feeding matrix circuit yields phase differences of ±90° and 0°. The feed circuit can obtain a reliable output signal, as there is only a small degree of deviation of output signal with variations in the line width. The feed circuit is simulated, fabricated, and evaluated for ISM band, and the measured characteristics agree well with the results of the simulation. The size of feed circuit is 45 (H) × 48 (W) × 3 (T) mm.

The contribution of hypothalamic macroglia to the regulation of energy homeostasis

PubMed Central

Buckman, Laura B.; Ellacott, Kate L. J.

2014-01-01

The hypothalamus is critical for the regulation of energy homeostasis. Genetic and pharmacologic studies have identified a number of key hypothalamic neuronal circuits that integrate signals controlling food intake and energy expenditure. Recently, studies have begun to emerge demonstrating a role for non-neuronal cell types in the regulation of energy homeostasis. In particular the potential importance of different glial cell types is increasingly being recognized. A number of studies have described changes in the activity of hypothalamic macroglia (principally astrocytes and tanycytes) in response to states of positive and negative energy balance, such as obesity and fasting. This article will review these studies and discuss how these findings are changing our understanding of the cellular mechanisms by which energy homeostasis is regulated. PMID:25374514

Circuit for echo and noise suppression of acoustic signals transmitted through a drill string

DOEpatents

Drumheller, D.S.; Scott, D.D.

1993-12-28

An electronic circuit for digitally processing analog electrical signals produced by at least one acoustic transducer is presented. In a preferred embodiment of the present invention, a novel digital time delay circuit is utilized which employs an array of First-in-First-out (FiFo) microchips. Also, a bandpass filter is used at the input to this circuit for isolating drill string noise and eliminating high frequency output. 20 figures.

Hybrid measurement chains for the SAS-C spacecraft. [advantages over analog signal processing circuits

NASA Technical Reports Server (NTRS)

Goeke, R. F.

1975-01-01

Spacecraft electronic systems usually demand tight packaging. It was this consideration which initially forced us to consider hybrid circuits for the analog signal processing circuits in the Small Astronomy Satellite-C (SAS-C) scientific payload. We gradually discovered that increased reliability, low power consumption, and reduced program costs all followed. This paper will attempt to share our laboratory's first experience with hybrid circuits and indicate those areas which we found to be important.

Dopamine D2 Receptor Signaling in the Nucleus Accumbens Comprises a Metabolic-Cognitive Brain Interface Regulating Metabolic Components of Glucose Reinforcement.

PubMed

Michaelides, Michael; Miller, Michael L; DiNieri, Jennifer A; Gomez, Juan L; Schwartz, Elizabeth; Egervari, Gabor; Wang, Gene Jack; Mobbs, Charles V; Volkow, Nora D; Hurd, Yasmin L

2017-11-01

Appetitive drive is influenced by coordinated interactions between brain circuits that regulate reinforcement and homeostatic signals that control metabolism. Glucose modulates striatal dopamine (DA) and regulates appetitive drive and reinforcement learning. Striatal DA D2 receptors (D2Rs) also regulate reinforcement learning and are implicated in glucose-related metabolic disorders. Nevertheless, interactions between striatal D2R and peripheral glucose have not been previously described. Here we show that manipulations involving striatal D2R signaling coincide with perseverative and impulsive-like responding for sucrose, a disaccharide consisting of fructose and glucose. Fructose conveys orosensory (ie, taste) reinforcement but does not convey metabolic (ie, nutrient-derived) reinforcement. Glucose however conveys orosensory reinforcement but unlike fructose, it is a major metabolic energy source, underlies sustained reinforcement, and activates striatal circuitry. We found that mice with deletion of dopamine- and cAMP-regulated neuronal phosphoprotein (DARPP-32) exclusively in D2R-expressing cells exhibited preferential D2R changes in the nucleus accumbens (NAc), a striatal region that critically regulates sucrose reinforcement. These changes coincided with perseverative and impulsive-like responding for sucrose pellets and sustained reinforcement learning of glucose-paired flavors. These mice were also characterized by significant glucose intolerance (ie, impaired glucose utilization). Systemic glucose administration significantly attenuated sucrose operant responding and D2R activation or blockade in the NAc bidirectionally modulated blood glucose levels and glucose tolerance. Collectively, these results implicate NAc D2R in regulating both peripheral glucose levels and glucose-dependent reinforcement learning behaviors and highlight the notion that glucose metabolic impairments arising from disrupted NAc D2R signaling are involved in compulsive and perseverative feeding behaviors.

CMOS image sensor with contour enhancement

NASA Astrophysics Data System (ADS)

Meng, Liya; Lai, Xiaofeng; Chen, Kun; Yuan, Xianghui

2010-10-01

Imitating the signal acquisition and processing of vertebrate retina, a CMOS image sensor with bionic pre-processing circuit is designed. Integration of signal-process circuit on-chip can reduce the requirement of bandwidth and precision of the subsequent interface circuit, and simplify the design of the computer-vision system. This signal pre-processing circuit consists of adaptive photoreceptor, spatial filtering resistive network and Op-Amp calculation circuit. The adaptive photoreceptor unit with a dynamic range of approximately 100 dB has a good self-adaptability for the transient changes in light intensity instead of intensity level itself. Spatial low-pass filtering resistive network used to mimic the function of horizontal cell, is composed of the horizontal resistor (HRES) circuit and OTA (Operational Transconductance Amplifier) circuit. HRES circuit, imitating dendrite of the neuron cell, comprises of two series MOS transistors operated in weak inversion region. Appending two diode-connected n-channel transistors to a simple transconductance amplifier forms the OTA Op-Amp circuit, which provides stable bias voltage for the gate of MOS transistors in HRES circuit, while serves as an OTA voltage follower to provide input voltage for the network nodes. The Op-Amp calculation circuit with a simple two-stage Op-Amp achieves the image contour enhancing. By adjusting the bias voltage of the resistive network, the smoothing effect can be tuned to change the effect of image's contour enhancement. Simulations of cell circuit and 16×16 2D circuit array are implemented using CSMC 0.5μm DPTM CMOS process.

Test Bench for Coupling and Shielding Magnetic Fields

NASA Astrophysics Data System (ADS)

Jordan, J.; Esteve, V.; Dede, E.; Sanchis, E.; Maset, E.; Ferreres, A.; Ejea, J. B.; Cases, C.

2016-05-01

This paper describes a test bench for training purposes, which uses a magnetic field generator to couple this magnetic field to a victim circuit. It can be very useful to test for magnetic susceptibility as well. The magnetic field generator consists of a board, which generates a variable current that flows into a printed circuit board with spiral tracks (noise generator). The victim circuit consists of a coaxial cable concentric with the spiral tracks and its generated magnetic field. The coaxial cable is part of a circuit which conducts a signal produced by a signal generator and a resistive load. In the paper three cases are studied. First, the transmitted signal from the signal generator uses the central conductor of the coaxial cable and the shield is floating. Second, the shield is short circuited at its ends (and thus forming a loop). Third, when connecting the shield in series with the inner conductor and therefore having the current flowing into the coax via the inner conductor and returning via the shield.

O-Glycosylation-mediated signaling circuit drives metastatic castration-resistant prostate cancer.

PubMed

Tzeng, Sheue-Fen; Tsai, Chin-Hsien; Chao, Tai-Kuang; Chou, Yu-Ching; Yang, Yu-Chih; Tsai, Mong-Hsun; Cha, Tai-Lung; Hsiao, Pei-Wen

2018-06-15

Disseminated castration-resistant prostate cancer (CRPC) is a common disease in men that is characterized by limited survival and resistance to androgen-deprivation therapy. The increase in human epidermal growth factor receptor 2 (HER2) signaling contributes to androgen receptor activity in a subset of patients with CRPC; however, enigmatically, HER2-targeted therapies have demonstrated a lack of efficacy in patients with CRPC. Aberrant glycosylation is a hallmark of cancer and involves key processes that support cancer progression. Using transcriptomic analysis of prostate cancer data sets, histopathologic examination of clinical specimens, and in vivo experiments of xenograft models, we reveal in this study a coordinated increase in glycan-binding protein, galectin-4, specific glycosyltransferases of core 1 synthase, glycoprotein- N-acetylgalactosamine 3-β-galactosyltransferase 1 (C1GALT1) and ST3 beta-galactoside α-2,3-sialyltransferase 1 (ST3GAL1), and resulting mucin-type O-glycans during the progression of CRPC. Furthermore, galectin-4 engaged with C1GALT1-dependent O-glycans to promote castration resistance and metastasis by activating receptor tyrosine kinase signaling and cancer cell stemness properties mediated by SRY-box 9 (SOX9). This galectin-glycan interaction up-regulated the MYC-dependent expression of C1GALT1 and ST3GAL1, which altered cellular mucin-type O-glycosylation to allow for galectin-4 binding. In clinical prostate cancer, high-level expression of C1GALT1 and galectin-4 together predict poor overall survival compared with low-level expression of C1GALT1 and galectin-4. In summary, MYC regulates abnormal O-glycosylation, thus priming cells for binding to galectin-4 and downstream signaling, which promotes castration resistance and metastasis.-Tzeng, S.-F., Tsai, C.-H., Chao, T.-K., Chou, Y.-C., Yang, Y.-C., Tsai, M.-H., Cha, T.-L., Hsiao, P.-W. O-Glycosylation-mediated signaling circuit drives metastatic castration-resistant prostate cancer.

Averaging of phase noise in PSK signals by an opto-electrical feed-forward circuit

NASA Astrophysics Data System (ADS)

Inoue, K.; Ohta, M.

2013-10-01

This paper proposes an opto-electrical feed-forward circuit that reduces phase noise in binary PSK signals by averaging the noise. Random and independent phase noise is averaged over several bit slots by externally modulating a phase-fluctuating PSK signal with feed-forward signal obtained from signal processing of the outputs of delay interferometers. The simulation results demonstrate a reduction in the phase noise.

JAK/Stat signaling regulates heart precursor diversification in Drosophila

PubMed Central

Johnson, Aaron N.; Mokalled, Mayssa H.; Haden, Tom N.; Olson, Eric N.

2011-01-01

Intercellular signal transduction pathways regulate the NK-2 family of transcription factors in a conserved gene regulatory network that directs cardiogenesis in both flies and mammals. The Drosophila NK-2 protein Tinman (Tin) was recently shown to regulate Stat92E, the Janus kinase (JAK) and Signal transducer and activator of transcription (Stat) pathway effector, in the developing mesoderm. To understand whether the JAK/Stat pathway also regulates cardiogenesis, we performed a systematic characterization of JAK/Stat signaling during mesoderm development. Drosophila embryos with mutations in the JAK/Stat ligand upd or in Stat92E have non-functional hearts with luminal defects and inappropriate cell aggregations. Using strong Stat92E loss-of-function alleles, we show that the JAK/Stat pathway regulates tin expression prior to heart precursor cell diversification. tin expression can be subdivided into four phases and, in Stat92E mutant embryos, the broad phase 2 expression pattern in the dorsal mesoderm does not restrict to the constrained phase 3 pattern. These embryos also have an expanded pericardial cell domain. We show the E(spl)-C gene HLHm5 is expressed in a pattern complementary to tin during phase 3 and that this expression is JAK/Stat dependent. In addition, E(spl)-C mutant embryos phenocopy the cardiac defects of Stat92E embryos. Mechanistically, JAK/Stat signals activate E(spl)-C genes to restrict Tin expression and the subsequent expression of the T-box transcription factor H15 to direct heart precursor diversification. This study is the first to characterize a role for the JAK/Stat pathway during cardiogenesis and identifies an autoregulatory circuit in which tin limits its own expression domain. PMID:21965617

Nrp2 is sufficient to instruct circuit formation of mitral-cells to mediate odour-induced attractive social responses.

PubMed

Inokuchi, Kasumi; Imamura, Fumiaki; Takeuchi, Haruki; Kim, Ryang; Okuno, Hiroyuki; Nishizumi, Hirofumi; Bito, Haruhiko; Kikusui, Takefumi; Sakano, Hitoshi

2017-07-21

Odour information induces various innate responses that are critical to the survival of the individual and for the species. An axon guidance molecule, Neuropilin 2 (Nrp2), is known to mediate targeting of olfactory sensory neurons (primary neurons), to the posteroventral main olfactory bulb (PV MOB) in mice. Here we report that Nrp2-positive (Nrp2 + ) mitral cells (MCs, second-order neurons) play crucial roles in transmitting attractive social signals from the PV MOB to the anterior part of medial amygdala (MeA). Semaphorin 3F, a repulsive ligand to Nrp2, regulates both migration of Nrp2 + MCs to the PV MOB and their axonal projection to the anterior MeA. In the MC-specific Nrp2 knockout mice, circuit formation of Nrp2 + MCs and odour-induced attractive social responses are impaired. In utero, electroporation demonstrates that activation of the Nrp2 gene in MCs is sufficient to instruct their circuit formation from the PV MOB to the anterior MeA.

Frequency Domain Multiplexing for Use With NaI[Tl] Detectors

NASA Astrophysics Data System (ADS)

Belling, Samuel; Coherent Collaboration

2017-09-01

A process used in many forms of signal communication known as multiplexing is adapted for the purpose of combining signals from NaI[Tl] detectors so that fewer digitizer channels can be used to process the signal information from large experiments within the COHERENT collaboration. Each signal is passed through a ringing circuit to modulate it with a characteristic frequency. Information about the signal can be extracted from its amplitude, frequency, and phase. Simulations in LTSpice show that an operational amplifier circuit with a parallel LRC feedback loop can serve as the modulating circuit. Several such circuits can be constructed and housed compactly in a unit, and fed to an inverting, summing amplifier with tunable gain, such that the signals are carried by one cable. The signals are analyzed based on a Fourier transform after being digitized. The results show that the energy, channel, and time of the original interaction can be recovered by this process. In some cases it is possible through filtering and deconvolution to recover the shape of the original signal. The effort is ongoing, but with the design presented it is possible to multiplex 10 detectors into a single digitizer channel. NSF REU Program at Duke University.

Quadrature demodulation based circuit implementation of pulse stream for ultrasonic signal FRI sparse sampling

NASA Astrophysics Data System (ADS)

Shoupeng, Song; Zhou, Jiang

2017-03-01

Converting ultrasonic signal to ultrasonic pulse stream is the key step of finite rate of innovation (FRI) sparse sampling. At present, ultrasonic pulse-stream-forming techniques are mainly based on digital algorithms. No hardware circuit that can achieve it has been reported. This paper proposes a new quadrature demodulation (QD) based circuit implementation method for forming an ultrasonic pulse stream. Elaborating on FRI sparse sampling theory, the process of ultrasonic signal is explained, followed by a discussion and analysis of ultrasonic pulse-stream-forming methods. In contrast to ultrasonic signal envelope extracting techniques, a quadrature demodulation method (QDM) is proposed. Simulation experiments were performed to determine its performance at various signal-to-noise ratios (SNRs). The circuit was then designed, with mixing module, oscillator, low pass filter (LPF), and root of square sum module. Finally, application experiments were carried out on pipeline sample ultrasonic flaw testing. The experimental results indicate that the QDM can accurately convert ultrasonic signal to ultrasonic pulse stream, and reverse the original signal information, such as pulse width, amplitude, and time of arrival. This technique lays the foundation for ultrasonic signal FRI sparse sampling directly with hardware circuitry.

Vehicle security apparatus and method

DOEpatents

Veligdan, J.T.

1996-02-13

A vehicle security apparatus for use in a motor vehicle is disclosed, the apparatus comprising an optical key, a receptacle, a receiver and at least one optical fiber. The optical key has a transmitter having at least one first preprogrammed coded signal stored in a first electric circuit. The receptacle receives the optical key and at least one transmittable coded optical signal from the transmitter corresponding to the at least one preprogrammed coded signal stored in the first electric circuit. The receiver compares the at least one transmittable coded optical signal to at least one second preprogrammed coded signal stored in a second electric circuit and the receiver is adapted to trigger switching effects for at least one of enabling starting the motor vehicle and starting the motor vehicle upon determination that the at least one transmittable coded optical signal corresponds to the at least one second preprogrammed signal in the second electric circuit. The at least one optical fiber is operatively connected between the receptacle and the receiver for carrying the optical signal from the receptacle to the receiver. Also disclosed is a method for permitting only authorized use of a motor vehicle. 7 figs.

Obesity treatment: novel peripheral targets

PubMed Central

Field, Benjamin C T; Chaudhri, Owais B; Bloom, Stephen R

2009-01-01

Our knowledge of the complex mechanisms underlying energy homeostasis has expanded enormously in recent years. Food intake and body weight are tightly regulated by the hypothalamus, brainstem and reward circuits, on the basis both of cognitive inputs and of diverse humoral and neuronal signals of nutritional status. Several gut hormones, including cholecystokinin, glucagon-like peptide-1, peptide YY, oxyntomodulin, amylin, pancreatic polypeptide and ghrelin, have been shown to play an important role in regulating short-term food intake. These hormones therefore represent potential targets in the development of novel anti-obesity drugs. This review focuses on the role of gut hormones in short- and long-term regulation of food intake, and on the current state of development of gut hormone-based obesity therapies. PMID:20002077

Stability analysis and compensation of a boost regulator with two-loop control

NASA Technical Reports Server (NTRS)

Wester, G. W.

1974-01-01

A useful stability measure has been demonstrated by Wester (1973) for switching regulators with a single feedback loop by applying the Nyquist criterion to the approximate loop gain determined by a time-averaging technique. This approach is extended and applied to the characterization, stability analysis, and compensation design of a switching regulator with two-loop control. The role and relative significance of each control loop is clarified on the basis of a description of circuit operation, and the major and minor loops are identified. In view of the inapplicability of linear feedback theory, describing functions of the feedback loops and power stage are derived, using small-signal analysis. Several phenomena revealed from an analysis of the major loop gain are discussed.

Annealing effects on hydrogenated diamond NOR logic circuits

NASA Astrophysics Data System (ADS)

Liu, J. W.; Oosato, H.; Liao, M. Y.; Imura, M.; Watanabe, E.; Koide, Y.

2018-04-01

Here, hydrogenated diamond (H-diamond) NOR logic circuits composed of two p-type enhancement-mode (E-mode) metal-oxide-semiconductor field-effect-transistors (MOSFETs) and a load resistor are fabricated and characterized. The fabrication process and the annealing effect on the electrical properties of the NOR logic circuit are demonstrated. There are distinct logical characteristics for the as-received and 300 °C annealed NOR logic circuits. When one or both input voltages for the E-mode MOSFETs are -10.0 V and "high" signals, output voltages respond 0 V and "low" signals. Instead, when both input voltages are 0 V and "low" signals, output voltage responds -10.0 V and a "high" signal. After annealing at 400 °C, the NOR logical characteristics are damaged, which is possibly attributed to the degradation of the H-diamond MOSFETs.

Digital automatic gain amplifier

NASA Technical Reports Server (NTRS)

Holley, L. D.; Ward, J. O. (Inventor)

1978-01-01

A circuit is described for adjusting the amplitude of a reference signal to a predetermined level so as to permit subsequent data signals to be interpreted correctly. The circuit includes an operational amplifier having a feedback circuit connected between an output terminal and an input terminal; a bank of relays operably connected to a plurality of resistors; and a comparator comparing an output voltage of the amplifier with a reference voltage and generating a compared signal responsive thereto. Means is provided for selectively energizing the relays according to the compared signal from the comparator until the output signal from the amplifier equals to the reference signal. A second comparator is provided for comparing the output of the amplifier with a second voltage source so as to illuminate a lamp when the output signal from the amplifier exceeds the second voltage.

Dendrosomatic Sonic Hedgehog Signaling in Hippocampal Neurons Regulates Axon Elongation

PubMed Central

Petralia, Ronald S.; Ott, Carolyn; Wang, Ya-Xian; Lippincott-Schwartz, Jennifer; Mattson, Mark P.

2015-01-01

The presence of Sonic Hedgehog (Shh) and its signaling components in the neurons of the hippocampus raises a question about what role the Shh signaling pathway may play in these neurons. We show here that activation of the Shh signaling pathway stimulates axon elongation in rat hippocampal neurons. This Shh-induced effect depends on the pathway transducer Smoothened (Smo) and the transcription factor Gli1. The axon itself does not respond directly to Shh; instead, the Shh signal transduction originates from the somatodendritic region of the neurons and occurs in neurons with and without detectable primary cilia. Upon Shh stimulation, Smo localization to dendrites increases significantly. Shh pathway activation results in increased levels of profilin1 (Pfn1), an actin-binding protein. Mutations in Pfn1's actin-binding sites or reduction of Pfn1 eliminate the Shh-induced axon elongation. These findings indicate that Shh can regulate axon growth, which may be critical for development of hippocampal neurons. SIGNIFICANCE STATEMENT Although numerous signaling mechanisms have been identified that act directly on axons to regulate their outgrowth, it is not known whether signals transduced in dendrites may also affect axon outgrowth. We describe here a transcellular signaling pathway in embryonic hippocampal neurons in which activation of Sonic Hedgehog (Shh) receptors in dendrites stimulates axon growth. The pathway involves the dendritic-membrane-associated Shh signal transducer Smoothened (Smo) and the transcription factor Gli, which induces the expression of the gene encoding the actin-binding protein profilin 1. Our findings suggest scenarios in which stimulation of Shh in dendrites results in accelerated outgrowth of the axon, which therefore reaches its presumptive postsynaptic target cell more quickly. By this mechanism, Shh may play critical roles in the development of hippocampal neuronal circuits. PMID:26658865

Auto-programmable impulse neural circuits

NASA Technical Reports Server (NTRS)

Watula, D.; Meador, J.

1990-01-01

Impulse neural networks use pulse trains to communicate neuron activation levels. Impulse neural circuits emulate natural neurons at a more detailed level than that typically employed by contemporary neural network implementation methods. An impulse neural circuit which realizes short term memory dynamics is presented. The operation of that circuit is then characterized in terms of pulse frequency modulated signals. Both fixed and programmable synapse circuits for realizing long term memory are also described. The implementation of a simple and useful unsupervised learning law is then presented. The implementation of a differential Hebbian learning rule for a specific mean-frequency signal interpretation is shown to have a straightforward implementation using digital combinational logic with a variation of a previously developed programmable synapse circuit. This circuit is expected to be exploited for simple and straightforward implementation of future auto-adaptive neural circuits.

The cholinergic anti-inflammatory pathway revisited.

PubMed

Murray, K; Reardon, C

2018-03-01

Inflammatory bowel disease negatively affects the quality of life of millions of patients around the world. Although the precise etiology of the disease remains elusive, aberrant immune system activation is an underlying cause. As such, therapies that selectively inhibit immune cell activation without broad immunosuppression are desired. Inhibition of immune cell activation preventing pro-inflammatory cytokine production through neural stimulation has emerged as one such treatment. These therapeutics are based on the discovery of the cholinergic anti-inflammatory pathway, a reflex arc that induces efferent vagal nerve signaling to reduce immune cell activation and consequently mortality during septic shock. Despite the success of preclinical and clinical trials, the neural circuitry and mechanisms of action of these immune-regulatory circuits are controversial. At the heart of this controversy is the protective effect of vagal nerve stimulation despite an apparent lack of neuroanatomical connections between the vagus and target organs. Additional studies have further emphasized the importance of sympathetic innervation of these organs, and that alternative neural circuits could be involved in neural regulation of the immune system. Such controversies also extend to the regulation of intestinal inflammation, with the importance of efferent vagus nerve signals in question. Experiments that better characterize these pathways have now been performed by Willemze et al. in this issue of Neurogastroenterology & Motility. These continued efforts will be critical to the development of better neurostimulator based therapeutics for inflammatory bowel disease. © 2018 John Wiley & Sons Ltd.

Hypothalamic Integration of Metabolic, Endocrine, and Circadian Signals in Fish: Involvement in the Control of Food Intake

PubMed Central

Delgado, María J.; Cerdá-Reverter, José M.; Soengas, José L.

2017-01-01

The regulation of food intake in fish is a complex process carried out through several different mechanisms in the central nervous system (CNS) with hypothalamus being the main regulatory center. As in mammals, a complex hypothalamic circuit including two populations of neurons: one co-expressing neuropeptide Y (NPY) and Agouti-related peptide (AgRP) and the second one population co-expressing pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) is involved in the integration of information relating to food intake control. The production and release of these peptides control food intake, and the production results from the integration of information of different nature such as levels of nutrients and hormones as well as circadian signals. The present review summarizes the knowledge and recent findings about the presence and functioning of these mechanisms in fish and their differences vs. the known mammalian model. PMID:28694769

Affective Brain-Computer Interfaces As Enabling Technology for Responsive Psychiatric Stimulation

PubMed Central

Widge, Alik S.; Dougherty, Darin D.; Moritz, Chet T.

2014-01-01

There is a pressing clinical need for responsive neurostimulators, which sense a patient’s brain activity and deliver targeted electrical stimulation to suppress unwanted symptoms. This is particularly true in psychiatric illness, where symptoms can fluctuate throughout the day. Affective BCIs, which decode emotional experience from neural activity, are a candidate control signal for responsive stimulators targeting the limbic circuit. Present affective decoders, however, cannot yet distinguish pathologic from healthy emotional extremes. Indiscriminate stimulus delivery would reduce quality of life and may be actively harmful. We argue that the key to overcoming this limitation is to specifically decode volition, in particular the patient’s intention to experience emotional regulation. Those emotion-regulation signals already exist in prefrontal cortex (PFC), and could be extracted with relatively simple BCI algorithms. We describe preliminary data from an animal model of PFC-controlled limbic brain stimulation and discuss next steps for pre-clinical testing and possible translation. PMID:25580443

Auto-Routable, Configurable, Daisy Chainable Data Acquisition System

NASA Technical Reports Server (NTRS)

Shuler, Robert L. (Inventor)

2005-01-01

A method and apparatus for an acquisition system includes a plurality of sensor input signal lines. At least one of the plurality of sensor input signal lines operatively connects to at least one of a plurality of amplifier circuits. At least one of the plurality of amplifier circuits operatively connects to at least one of a plurality of filter circuits.

Analog Module Architecture for Space-Qualified Field-Programmable Mixed-Signal Arrays

NASA Technical Reports Server (NTRS)

Edwards, R. Timothy; Strohbehn, Kim; Jaskulek, Steven E.; Katz, Richard

1999-01-01

Spacecraft require all manner of both digital and analog circuits. Onboard digital systems are constructed almost exclusively from field-programmable gate array (FPGA) circuits providing numerous advantages over discrete design including high integration density, high reliability, fast turn-around design cycle time, lower mass, volume, and power consumption, and lower parts acquisition and flight qualification costs. Analog and mixed-signal circuits perform tasks ranging from housekeeping to signal conditioning and processing. These circuits are painstakingly designed and built using discrete components due to a lack of options for field-programmability. FPAA (Field-Programmable Analog Array) and FPMA (Field-Programmable Mixed-signal Array) parts exist but not in radiation-tolerant technology and not necessarily in an architecture optimal for the design of analog circuits for spaceflight applications. This paper outlines an architecture proposed for an FPAA fabricated in an existing commercial digital CMOS process used to make radiation-tolerant antifuse-based FPGA devices. The primary concerns are the impact of the technology and the overall array architecture on the flexibility of programming, the bandwidth available for high-speed analog circuits, and the accuracy of the components for high-performance applications.

Brassinosteroid-Induced Transcriptional Repression and Dephosphorylation-Dependent Protein Degradation Negatively Regulate BIN2-Interacting AIF2 (a BR Signaling-Negative Regulator) bHLH Transcription Factor.

PubMed

Kim, Yoon; Song, Ji-Hye; Park, Seon-U; Jeong, You-Seung; Kim, Soo-Hwan

2017-02-01

Brassinosteroids (BRs) are plant polyhydroxy-steroids that play important roles in plant growth and development via extensive signal integration through direct interactions between regulatory components of different signaling pathways. Recent studies have shown that diverse helix-loop-helix/basic helix-loop-helix (HLH/bHLH) family proteins are actively involved in control of BR signaling pathways and interact with other signaling pathways. In this study, we show that ATBS1-INTERACTING FACTOR 2 (AIF2), a nuclear-localized atypical bHLH transcription factor, specifically interacts with BRASSINOSTEROID-INSENSITIVE 2 (BIN2) among other BR signaling molecules. Overexpression of AIF2 down-regulated transcript expression of growth-promoting genes, thus resulting in retardation of growth. AIF2 renders plants hyposensitive to BR-induced root growth inhibition, but shows little effects on BR-promoted hypocotyl elongation. Notably, AIF2 was dephosphorylated by BR, and the dephosphorylated AIF2 was subject to proteasome-mediated degradation. AIF2 degradation was greatly induced by BR and ABA, but relatively slightly by other hormones such as auxin, gibberellin, cytokinin and ethylene. Moreover, AIF2 transcription was significantly suppressed by a BRI1/BZR1-mediated BR signaling pathway through a direct binding of BRASSINAZOLE RESISTANT 1 (BZR1) to the BR response element (BRRE) region of the AIF2 promoter. In conclusion, our study suggests that BIN2-driven AIF2 phosphorylation could augment the BIN2/AIF2-mediated negative circuit of BR signaling pathways, and the BR-induced transcriptional repression and protein degradation negatively regulate AIF2 transcription factor, reinforcing the BZR1/BES1-mediated positive BR signaling pathway. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Electronic filters, repeated signal charge conversion apparatus, hearing aids and methods

NASA Technical Reports Server (NTRS)

Morley, Jr., Robert E. (Inventor); Engebretson, A. Maynard (Inventor); Engel, George L. (Inventor); Sullivan, Thomas J. (Inventor)

1993-01-01

An electronic filter for filtering an electrical signal. Signal processing circuitry therein includes a logarithmic filter having a series of filter stages with inputs and outputs in cascade and respective circuits associated with the filter stages for storing electrical representations of filter parameters. The filter stages include circuits for respectively adding the electrical representations of the filter parameters to the electrical signal to be filtered thereby producing a set of filter sum signals. At least one of the filter stages includes circuitry for producing a filter signal in substantially logarithmic form at its output by combining a filter sum signal for that filter stage with a signal from an output of another filter stage. The signal processing circuitry produces an intermediate output signal, and a multiplexer connected to the signal processing circuit multiplexes the intermediate output signal with the electrical signal to be filtered so that the logarithmic filter operates as both a logarithmic prefilter and a logarithmic postfilter. Other electronic filters, signal conversion apparatus, electroacoustic systems, hearing aids and methods are also disclosed.

Dopamine-Modulated Recurrent Corticoefferent Feedback in Primary Sensory Cortex Promotes Detection of Behaviorally Relevant Stimuli

PubMed Central

Handschuh, Juliane

2014-01-01

Dopaminergic neurotransmission in primary auditory cortex (AI) has been shown to be involved in learning and memory functions. Moreover, dopaminergic projections and D1/D5 receptor distributions display a layer-dependent organization, suggesting specific functions in the cortical circuitry. However, the circuit effects of dopaminergic neurotransmission in sensory cortex and their possible roles in perception, learning, and memory are largely unknown. Here, we investigated layer-specific circuit effects of dopaminergic neuromodulation using current source density (CSD) analysis in AI of Mongolian gerbils. Pharmacological stimulation of D1/D5 receptors increased auditory-evoked synaptic currents in infragranular layers, prolonging local thalamocortical input via positive feedback between infragranular output and granular input. Subsequently, dopamine promoted sustained cortical activation by prolonged recruitment of long-range corticocortical networks. A detailed circuit analysis combining layer-specific intracortical microstimulation (ICMS), CSD analysis, and pharmacological cortical silencing revealed that cross-laminar feedback enhanced by dopamine relied on a positive, fast-acting recurrent corticoefferent loop, most likely relayed via local thalamic circuits. Behavioral signal detection analysis further showed that activation of corticoefferent output by infragranular ICMS, which mimicked auditory activation under dopaminergic influence, was most effective in eliciting a behaviorally detectable signal. Our results show that D1/D5-mediated dopaminergic modulation in sensory cortex regulates positive recurrent corticoefferent feedback, which enhances states of high, persistent activity in sensory cortex evoked by behaviorally relevant stimuli. In boosting horizontal network interactions, this potentially promotes the readout of task-related information from cortical synapses and improves behavioral stimulus detection. PMID:24453315

Understanding Biological Regulation Through Synthetic Biology.

PubMed

Bashor, Caleb J; Collins, James J

2018-05-20

Engineering synthetic gene regulatory circuits proceeds through iterative cycles of design, building, and testing. Initial circuit designs must rely on often-incomplete models of regulation established by fields of reductive inquiry-biochemistry and molecular and systems biology. As differences in designed and experimentally observed circuit behavior are inevitably encountered, investigated, and resolved, each turn of the engineering cycle can force a resynthesis in understanding of natural network function. Here, we outline research that uses the process of gene circuit engineering to advance biological discovery. Synthetic gene circuit engineering research has not only refined our understanding of cellular regulation but furnished biologists with a toolkit that can be directed at natural systems to exact precision manipulation of network structure. As we discuss, using circuit engineering to predictively reorganize, rewire, and reconstruct cellular regulation serves as the ultimate means of testing and understanding how cellular phenotype emerges from systems-level network function.

Central nervous system mechanisms linking the consumption of palatable high-fat diets to the defense of greater adiposity.

PubMed

Ryan, Karen K; Woods, Stephen C; Seeley, Randy J

2012-02-08

The central nervous system (CNS) plays key role in the homeostatic regulation of body weight. Satiation and adiposity signals, providing acute and chronic information about available fuel, are produced in the periphery and act in the brain to influence energy intake and expenditure, resulting in the maintenance of stable adiposity. Diet-induced obesity (DIO) does not result from a failure of these central homeostatic circuits. Rather, the threshold for defended adiposity is increased in environments providing ubiquitous access to palatable, high-fat foods, making it difficult to achieve and maintain weight loss. Consequently, mechanisms by which nutritional environments interact with central homeostatic circuits to influence the threshold for defended adiposity represent critical targets for therapeutic intervention. Copyright © 2012 Elsevier Inc. All rights reserved.

Arbitrary waveform generator to improve laser diode driver performance

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

Fulkerson, Jr, Edward Steven

2015-11-03

An arbitrary waveform generator modifies the input signal to a laser diode driver circuit in order to reduce the overshoot/undershoot and provide a "flat-top" signal to the laser diode driver circuit. The input signal is modified based on the original received signal and the feedback from the laser diode by measuring the actual current flowing in the laser diode after the original signal is applied to the laser diode.

Mitochondrial proticity and ROS signaling: lessons from the uncoupling proteins.

PubMed

Mailloux, Ryan J; Harper, Mary-Ellen

2012-09-01

Fifty years since Peter Mitchell proposed the theory of chemiosmosis, the transformation of cellular redox potential into ATP synthetic capacity is still a widely recognized function of mitochondria. Mitchell used the term 'proticity' to describe the force and flow of the proton circuit across the inner membrane. When the proton gradient is coupled to ATP synthase activity, the conversion of fuel to ATP is efficient. However, uncoupling proteins (UCPs) can cause proton leaks resulting in poor fuel conversion efficiency, and some UCPs might control mitochondrial reactive oxygen species (ROS) production. Once viewed as toxic metabolic waste, ROS are now implicated in cell signaling and regulation. Here, we discuss the role of mitochondrial proticity in the context of ROS production and signaling. Copyright © 2012 Elsevier Ltd. All rights reserved.

Distinctive striatal dopamine signaling after dieting and gastric bypass.

PubMed

Hankir, Mohammed K; Ashrafian, Hutan; Hesse, Swen; Horstmann, Annette; Fenske, Wiebke K

2015-05-01

Highly palatable and/or calorically dense foods, such as those rich in fat, engage the striatum to govern and set complex behaviors. Striatal dopamine signaling has been implicated in hedonic feeding and the development of obesity. Dieting and bariatric surgery have markedly different outcomes on weight loss, yet how these interventions affect central homeostatic and food reward processing remains poorly understood. Here, we propose that dieting and gastric bypass produce distinct changes in peripheral factors with known roles in regulating energy homeostasis, resulting in differential modulation of nigrostriatal and mesolimbic dopaminergic reward circuits. Enhancement of intestinal fat metabolism after gastric bypass may also modify striatal dopamine signaling contributing to its unique long-term effects on feeding behavior and body weight in obese individuals. Copyright © 2015 Elsevier Ltd. All rights reserved.

Signal Digitizer and Cross-Correlation Application Specific Integrated Circuit

NASA Technical Reports Server (NTRS)

Baranauskas, Gytis (Inventor); Lim, Boon H. (Inventor); Baranauskas, Dalius (Inventor); Zelenin, Denis (Inventor); Kangaslahti, Pekka (Inventor); Tanner, Alan B. (Inventor)

2017-01-01

According to one embodiment, a cross-correlator comprises a plurality of analog front ends (AFEs), a cross-correlation circuit and a data serializer. Each of the AFEs comprises a variable gain amplifier (VGA) and a corresponding analog-to-digital converter (ADC) in which the VGA receives and modifies a unique analog signal associates with a measured analog radio frequency (RF) signal and the ADC produces digital data associated with the modified analog signal. Communicatively coupled to the AFEs, the cross-correlation circuit performs a cross-correlation operation on the digital data produced from different measured analog RF signals. The data serializer is communicatively coupled to the summing and cross-correlating matrix and continuously outputs a prescribed amount of the correlated digital data.

Circadian pacemaking in cells and circuits of the suprachiasmatic nucleus.

PubMed

Hastings, M H; Brancaccio, M; Maywood, E S

2014-01-01

The suprachiasmatic nucleus (SCN) of the hypothalamus is the principal circadian pacemaker of the brain. It co-ordinates the daily rhythms of sleep and wakefulness, as well as physiology and behaviour, that set the tempo to our lives. Disturbance of this daily pattern, most acutely with jet-lag but more insidiously with rotational shift-work, can have severely deleterious effects for mental function and long-term health. The present review considers recent developments in our understanding of the properties of the SCN that make it a robust circadian time-keeper. It first focuses on the intracellular transcriptional/ translational feedback loops (TTFL) that constitute the cellular clockwork of the SCN neurone. Daily timing by these loops pivots around the negative regulation of the Period (Per) and Cryptochrome (Cry) genes by their protein products. The period of the circadian cycle is set by the relative stability of Per and Cry proteins, and this can be controlled by both genetic and pharmacological interventions. It then considers the function of these feedback loops in the context of cytosolic signalling by cAMP and intracellular calcium ([Ca(2+) ]i ), which are both outputs from, and inputs to, the TTFL, as well as the critical role of vasoactive intestinal peptide (VIP) signalling in synchronising cellular clocks across the SCN. Synchronisation by VIP in the SCN is paracrine, operating over an unconventionally long time frame (i.e. 24 h) and wide spatial domain, mediated via the cytosolic pathways upstream of the TTFL. Finally, we show how intersectional pharmacogenetics can be used to control G-protein-coupled signalling in individual SCN neurones, and how manipulation of Gq/[Ca(2+) ]i -signalling in VIP neurones can re-programme the circuit-level encoding of circadian time. Circadian pacemaking in the SCN therefore provides an unrivalled context in which to understand how a complex, adaptive behaviour can be organised by the dynamic activity of a relatively few gene products, operating in a clearly defined neuronal circuit, with both cell-autonomous and emergent, circuit-level properties. © 2014 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of The British Society for Neuroendocrinology.

Reward signal in a recurrent circuit drives appetitive long-term memory formation.

PubMed

Ichinose, Toshiharu; Aso, Yoshinori; Yamagata, Nobuhiro; Abe, Ayako; Rubin, Gerald M; Tanimoto, Hiromu

2015-11-17

Dopamine signals reward in animal brains. A single presentation of a sugar reward to Drosophila activates distinct subsets of dopamine neurons that independently induce short- and long-term olfactory memories (STM and LTM, respectively). In this study, we show that a recurrent reward circuit underlies the formation and consolidation of LTM. This feedback circuit is composed of a single class of reward-signaling dopamine neurons (PAM-α1) projecting to a restricted region of the mushroom body (MB), and a specific MB output cell type, MBON-α1, whose dendrites arborize that same MB compartment. Both MBON-α1 and PAM-α1 neurons are required during the acquisition and consolidation of appetitive LTM. MBON-α1 additionally mediates the retrieval of LTM, which is dependent on the dopamine receptor signaling in the MB α/β neurons. Our results suggest that a reward signal transforms a nascent memory trace into a stable LTM using a feedback circuit at the cost of memory specificity.

Mixed Signal Learning by Spike Correlation Propagation in Feedback Inhibitory Circuits

PubMed Central

Hiratani, Naoki; Fukai, Tomoki

2015-01-01

The brain can learn and detect mixed input signals masked by various types of noise, and spike-timing-dependent plasticity (STDP) is the candidate synaptic level mechanism. Because sensory inputs typically have spike correlation, and local circuits have dense feedback connections, input spikes cause the propagation of spike correlation in lateral circuits; however, it is largely unknown how this secondary correlation generated by lateral circuits influences learning processes through STDP, or whether it is beneficial to achieve efficient spike-based learning from uncertain stimuli. To explore the answers to these questions, we construct models of feedforward networks with lateral inhibitory circuits and study how propagated correlation influences STDP learning, and what kind of learning algorithm such circuits achieve. We derive analytical conditions at which neurons detect minor signals with STDP, and show that depending on the origin of the noise, different correlation timescales are useful for learning. In particular, we show that non-precise spike correlation is beneficial for learning in the presence of cross-talk noise. We also show that by considering excitatory and inhibitory STDP at lateral connections, the circuit can acquire a lateral structure optimal for signal detection. In addition, we demonstrate that the model performs blind source separation in a manner similar to the sequential sampling approximation of the Bayesian independent component analysis algorithm. Our results provide a basic understanding of STDP learning in feedback circuits by integrating analyses from both dynamical systems and information theory. PMID:25910189

Distortion of the convolution spectra of PSK signals in frequency multipliers

NASA Astrophysics Data System (ADS)

Viniarskii, V. F.; Marchenko, V. F.; Petrin, Iu. M.

1983-09-01

The influence of the input and output circuits of frequency multipliers on the convolution spectrum of binary and ternary PSK signals is examined. It is shown that transient processes caused by the phase switching of the input signal lead to the amplitude-phase modulation of the harmonic signal. Experimental results are presented on the balance circuits of MOS varactor doublers and triplers.

Neural Networks For Demodulation Of Phase-Modulated Signals

NASA Technical Reports Server (NTRS)

Altes, Richard A.

1995-01-01

Hopfield neural networks proposed for demodulating quadrature phase-shift-keyed (QPSK) signals carrying digital information. Networks solve nonlinear integral equations prior demodulation circuits cannot solve. Consists of set of N operational amplifiers connected in parallel, with weighted feedback from output terminal of each amplifier to input terminals of other amplifiers. Used to solve signal processing problems. Implemented as analog very-large-scale integrated circuit that achieves rapid convergence. Alternatively, implemented as digital simulation of such circuit. Also used to improve phase estimation performance over that of phase-locked loop.

High-Voltage-Input Level Translator Using Standard CMOS

NASA Technical Reports Server (NTRS)

Yager, Jeremy A.; Mojarradi, Mohammad M.; Vo, Tuan A.; Blalock, Benjamin J.

2011-01-01

proposed integrated circuit would translate (1) a pair of input signals having a low differential potential and a possibly high common-mode potential into (2) a pair of output signals having the same low differential potential and a low common-mode potential. As used here, "low" and "high" refer to potentials that are, respectively, below or above the nominal supply potential (3.3 V) at which standard complementary metal oxide/semiconductor (CMOS) integrated circuits are designed to operate. The input common-mode potential could lie between 0 and 10 V; the output common-mode potential would be 2 V. This translation would make it possible to process the pair of signals by use of standard 3.3-V CMOS analog and/or mixed-signal (analog and digital) circuitry on the same integrated-circuit chip. A schematic of the circuit is shown in the figure. Standard 3.3-V CMOS circuitry cannot withstand input potentials greater than about 4 V. However, there are many applications that involve low-differential-potential, high-common-mode-potential input signal pairs and in which standard 3.3-V CMOS circuitry, which is relatively inexpensive, would be the most appropriate circuitry for performing other functions on the integrated-circuit chip that handles the high-potential input signals. Thus, there is a need to combine high-voltage input circuitry with standard low-voltage CMOS circuitry on the same integrated-circuit chip. The proposed circuit would satisfy this need. In the proposed circuit, the input signals would be coupled into both a level-shifting pair and a common-mode-sensing pair of CMOS transistors. The output of the level-shifting pair would be fed as input to a differential pair of transistors. The resulting differential current output would pass through six standoff transistors to be mirrored into an output branch by four heterojunction bipolar transistors. The mirrored differential current would be converted back to potential by a pair of diode-connected transistors, which, by virtue of being identical to the input transistors, would reproduce the input differential potential at the output

TRPC6 fulfills a calcineurin signaling circuit during pathologic cardiac remodeling

PubMed Central

Kuwahara, Koichiro; Wang, Yanggan; McAnally, John; Richardson, James A.; Bassel-Duby, Rhonda; Hill, Joseph A.; Olson, Eric N.

2006-01-01

The heart responds to injury and chronic pressure overload by pathologic growth and remodeling, which frequently result in heart failure and sudden death. Calcium-dependent signaling pathways promote cardiac growth and associated changes in gene expression in response to stress. The calcium/calmodulin-dependent phosphatase calcineurin, which signals to nuclear factor of activated T cells (NFAT) transcription factors, serves as a transducer of calcium signals and is sufficient and necessary for pathologic cardiac hypertrophy and remodeling. Transient receptor potential (TRP) proteins regulate cation entry into cells in response to a variety of signals, and in skeletal muscle, expression of TRP cation channel, subfamily C, member 3 (TRPC3) is increased in response to neurostimulation and calcineurin signaling. Here we show that TRPC6 was upregulated in mouse hearts in response to activated calcineurin and pressure overload, as well as in failing human hearts. Two conserved NFAT consensus sites in the promoter of the TRPC6 gene conferred responsiveness to cardiac stress. Cardiac-specific overexpression of TRPC6 in transgenic mice resulted in heightened sensitivity to stress, a propensity for lethal cardiac growth and heart failure, and an increase in NFAT-dependent expression of β–myosin heavy chain, a sensitive marker for pathologic hypertrophy. These findings implicate TRPC6 as a positive regulator of calcineurin-NFAT signaling and a key component of a calcium-dependent regulatory loop that drives pathologic cardiac remodeling. PMID:17099778

Neural control of locomotion and training-induced plasticity after spinal and cerebral lesions.

PubMed

Knikou, Maria

2010-10-01

Standing and walking require a plethora of sensorimotor interactions that occur throughout the nervous system. Sensory afferent feedback plays a crucial role in the rhythmical muscle activation pattern, as it affects through spinal reflex circuits the spinal neuronal networks responsible for inducing and maintaining rhythmicity, drives short-term and long-term re-organization of the brain and spinal cord circuits, and contributes to recovery of walking after locomotor training. Therefore, spinal circuits integrating sensory signals are adjustable networks with learning capabilities. In this review, I will synthesize the mechanisms underlying phase-dependent modulation of spinal reflexes in healthy humans as well as those with spinal or cerebral lesions along with findings on afferent regulation of spinal reflexes and central pattern generator in reduced animal preparations. Recovery of walking after locomotor training has been documented in numerous studies but the re-organization of spinal interneuronal and cortical circuits need to be further explored at cellular and physiological levels. For maximizing sensorimotor recovery in people with spinal or cerebral lesions, a multidisciplinary approach (rehabilitation, pharmacology, and electrical stimulation) delivered during various sensorimotor constraints is needed. Copyright 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Circuit For Control Of Electromechanical Prosthetic Hand

NASA Technical Reports Server (NTRS)

Bozeman, Richard J., Jr.

1995-01-01

Proposed circuit for control of electromechanical prosthetic hand derives electrical control signals from shoulder movements. Updated, electronic version of prosthesis, that includes two hooklike fingers actuated via cables from shoulder harness. Circuit built around favored shoulder harness, provides more dexterous movement, without incurring complexity of computer-controlled "bionic" or hydraulically actuated devices. Additional harness and potentiometer connected to similar control circuit mounted on other shoulder. Used to control stepping motor rotating hand about prosthetic wrist to one of number of angles consistent with number of digital outputs. Finger-control signals developed by circuit connected to first shoulder harness transmitted to prosthetic hand via sliprings at prosthetic wrist joint.

Extended Range Passive Wireless Tag System and Method

NASA Technical Reports Server (NTRS)

Fink, Patrick W. (Inventor); Lin, Gregory Y. (Inventor); Kennedy, Timothy F. (Inventor)

2013-01-01

A passive wireless tag assembly comprises a plurality of antennas and transmission lines interconnected with circuitry and constructed and arranged in a Van Atta array or configuration to reflect an interrogator signal in the direction from where it came. The circuitry may comprise at least one surface acoustic wave (SAW)-based circuit that functions as a signal reflector and is operatively connected with an information circuit. In another embodiment, at least one delay circuit and/or at least one passive modulation circuit(s) are utilized. In yet another embodiment, antennas connected to SAW-based devices are mounted to at least one of the orthogonal surfaces of a corner reflector.

Contact stress sensor

DOEpatents

Kotovsky, Jack

2014-02-11

A method for producing a contact stress sensor that includes one or more MEMS fabricated sensor elements, where each sensor element of includes a thin non-recessed portion, a recessed portion and a pressure sensitive element adjacent to the recessed portion. An electric circuit is connected to the pressure sensitive element. The circuit includes a pressure signal circuit element configured to provide a signal upon movement of the pressure sensitive element.

Contact stress sensor

DOEpatents

Kotovsky, Jack [Oakland, CA

2012-02-07

A contact stress sensor includes one or more MEMS fabricated sensor elements, where each sensor element of includes a thin non-recessed portion, a recessed portion and a pressure sensitive element adjacent to the recessed portion. An electric circuit is connected to the pressure sensitive element. The circuit includes a thermal compensator and a pressure signal circuit element configured to provide a signal upon movement of the pressure sensitive element.

Safe arming system for two-explosive munitions

DOEpatents

Jaroska, Miles F.; Niven, William A.; Morrison, Jasper J.

1978-01-01

A system for safely and positively detonating high-explosive munitions, including a source of electrical signals, a split-phase square-loop transformer responsive solely to a unique series of signals from the source for charging an energy storage circuit through a voltage doubling circuit, and a spark-gap trigger for initiating discharge of the energy in the storage circuit to actuate a detonator and thereby fire the munitions.

Graphene radio frequency receiver integrated circuit.

PubMed

Han, Shu-Jen; Garcia, Alberto Valdes; Oida, Satoshi; Jenkins, Keith A; Haensch, Wilfried

2014-01-01

Graphene has attracted much interest as a future channel material in radio frequency electronics because of its superior electrical properties. Fabrication of a graphene integrated circuit without significantly degrading transistor performance has proven to be challenging, posing one of the major bottlenecks to compete with existing technologies. Here we present a fabrication method fully preserving graphene transistor quality, demonstrated with the implementation of a high-performance three-stage graphene integrated circuit. The circuit operates as a radio frequency receiver performing signal amplification, filtering and downconversion mixing. All circuit components are integrated into 0.6 mm(2) area and fabricated on 200 mm silicon wafers, showing the unprecedented graphene circuit complexity and silicon complementary metal-oxide-semiconductor process compatibility. The demonstrated circuit performance allow us to use graphene integrated circuit to perform practical wireless communication functions, receiving and restoring digital text transmitted on a 4.3-GHz carrier signal.

Functional Laser Trimming Of Thin Film Resistors On Silicon ICs

NASA Astrophysics Data System (ADS)

Mueller, Michael J.; Mickanin, Wes

1986-07-01

Modern Laser Wafer Trimming (LWT) technology achieves exceptional analog circuit performance and precision while maintain-ing the advantages of high production throughput and yield. Microprocessor-driven instrumentation has both emphasized the role of data conversion circuits and demanded sophisticated signal conditioning functions. Advanced analog semiconductor circuits with bandwidths over 1 GHz, and high precision, trimmable, thin-film resistors meet many of todays emerging circuit requirements. Critical to meeting these requirements are optimum choices of laser characteristics, proper materials, trimming process control, accurate modeling of trimmed resistor performance, and appropriate circuit design. Once limited exclusively to hand-crafted, custom integrated circuits, designs are now available in semi-custom circuit configurations. These are similar to those provided for digital designs and supported by computer-aided design (CAD) tools. Integrated with fully automated measurement and trimming systems, these quality circuits can now be produced in quantity to meet the requirements of communications, instrumentation, and signal processing markets.

Graphene radio frequency receiver integrated circuit

NASA Astrophysics Data System (ADS)

Han, Shu-Jen; Garcia, Alberto Valdes; Oida, Satoshi; Jenkins, Keith A.; Haensch, Wilfried

2014-01-01

Graphene has attracted much interest as a future channel material in radio frequency electronics because of its superior electrical properties. Fabrication of a graphene integrated circuit without significantly degrading transistor performance has proven to be challenging, posing one of the major bottlenecks to compete with existing technologies. Here we present a fabrication method fully preserving graphene transistor quality, demonstrated with the implementation of a high-performance three-stage graphene integrated circuit. The circuit operates as a radio frequency receiver performing signal amplification, filtering and downconversion mixing. All circuit components are integrated into 0.6 mm2 area and fabricated on 200 mm silicon wafers, showing the unprecedented graphene circuit complexity and silicon complementary metal-oxide-semiconductor process compatibility. The demonstrated circuit performance allow us to use graphene integrated circuit to perform practical wireless communication functions, receiving and restoring digital text transmitted on a 4.3-GHz carrier signal.

Signal processing: opportunities for superconductive circuits

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

Ralston, R.W.

1985-03-01

Prime motivators in the evolution of increasingly sophisticated communication and detection systems are the needs for handling ever wider signal bandwidths and higher data processing speeds. These same needs drive the development of electronic device technology. Until recently the superconductive community has been tightly focused on digital devices for high speed computers. The purpose of this paper is to describe opportunities and challenges which exist for both analog and digital devices in a less familiar area, that of wideband signal processing. The function and purpose of analog signal-processing components, including matched filters, correlators and Fourier transformers, will be described andmore » examples of superconductive implementations given. A canonic signal-processing system is then configured using these components in combination with analog/digital converters and digital output circuits to highlight the important issues of dynamic range, accuracy and equivalent computation rate. Superconductive circuits hold promise for processing signals of 10-GHz bandwidth. Signal processing systems, however, can be properly designed and implemented only through a synergistic combination of the talents of device physicists, circuit designers, algorithm architects and system engineers. An immediate challenge to the applied superconductivity community is to begin sharing ideas with these other researchers.« less

Electronic bidirectional valve circuit prevents crossover distortion and threshold effect

NASA Technical Reports Server (NTRS)

Kernick, A.

1966-01-01

Four-terminal network forms a bidirectional valve which will switch or alternate an ac signal without crossover distortion or threshold effect. In this network, an isolated control signal is sufficient for circuit turn-on.

Nonreciprocal signal routing in an active quantum network

NASA Astrophysics Data System (ADS)

Metelmann, A.; Türeci, H. E.

2018-04-01

As superconductor quantum technologies are moving towards large-scale integrated circuits, a robust and flexible approach to routing photons at the quantum level becomes a critical problem. Active circuits, which contain parametrically driven elements selectively embedded in the circuit, offer a viable solution. Here, we present a general strategy for routing nonreciprocally quantum signals between two sites of a given lattice of oscillators, implementable with existing superconducting circuit components. Our approach makes use of a dual lattice of overdamped oscillators linking the nodes of the main lattice. Solutions for spatially selective driving of the lattice elements can be found, which optimally balance coherent and dissipative hopping of microwave photons to nonreciprocally route signals between two given nodes. In certain lattices these optimal solutions are obtained at the exceptional point of the dynamical matrix of the network. We also demonstrate that signal and noise transmission characteristics can be separately optimized.

Toward Wireless Health Monitoring via an Analog Signal Compression-Based Biosensing Platform.

PubMed

Zhao, Xueyuan; Sadhu, Vidyasagar; Le, Tuan; Pompili, Dario; Javanmard, Mehdi

2018-06-01

Wireless all-analog biosensor design for the concurrent microfluidic and physiological signal monitoring is presented in this paper. The key component is an all-analog circuit capable of compressing two analog sources into one analog signal by the analog joint source-channel coding (AJSCC). Two circuit designs are discussed, including the stacked-voltage-controlled voltage source (VCVS) design with the fixed number of levels, and an improved design, which supports a flexible number of AJSCC levels. Experimental results are presented on the wireless biosensor prototype, composed of printed circuit board realizations of the stacked-VCVS design. Furthermore, circuit simulation and wireless link simulation results are presented on the improved design. Results indicate that the proposed wireless biosensor is well suited for sensing two biological signals simultaneously with high accuracy, and can be applied to a wide variety of low-power and low-cost wireless continuous health monitoring applications.

Cognitive Radio Low-Energy Signal Analysis Sensor Integrated Circuits (CLASIC): A Broadband Mixed-Signal Iterative Down Conversion Spectrum Analyzer for Signal Recognition Applications

DTIC Science & Technology

2015-12-01

AFRL-RY-WP-TR-2015-0144 COGNITIVE RADIO LOW-ENERGY SIGNAL ANALYSIS SENSOR INTEGRATED CIRCUITS (CLASIC) A Broadband Mixed-Signal Iterative Down...See additional restrictions described on inside pages STINFO COPY AIR FORCE RESEARCH LABORATORY SENSORS DIRECTORATE WRIGHT-PATTERSON AIR FORCE...Signature// TODD KASTLE, Chief Spectrum Warfare Division Sensors Directorate This report is published in the interest of scientific and technical

HMBA Enhances Prostratin-Induced Activation of Latent HIV-1 via Suppressing the Expression of Negative Feedback Regulator A20/TNFAIP3 in NF-κB Signaling.

PubMed

Chen, Duchu; Wang, Huiping; Aweya, Jude Juventus; Chen, Yanheng; Chen, Meihua; Wu, Xiaomeng; Chen, Xiaonan; Lu, Jing; Chen, Ruichuan; Liu, Min

2016-01-01

In the past decade, much emphasis has been put on the transcriptional activation of HIV-1, which is proposed as a promised strategy for eradicating latent HIV-1 provirus. Two drugs, prostratin and hexamethylene bisacetamide (HMBA), have shown potent effects as inducers for releasing HIV-1 latency when used alone or in combination, although their cellular target(s) are currently not well understood, especially under drug combination. Here, we have shown that HMBA and prostratin synergistically release HIV-1 latency via different mechanisms. While prostratin strongly stimulates HMBA-induced HIV-1 transcription via improved P-TEFb activation, HMBA is capable of boosting NF-κB-dependent transcription initiation by suppressing prostratin-induced expression of the deubiquitinase A20, a negative feedback regulator in the NF-κB signaling pathway. In addition, HMBA was able to increase prostratin-induced phosphorylation and degradation of NF-κB inhibitor IκBα, thereby enhancing and prolonging prostratin-induced nuclear translocation of NF-κB, a prerequisite for stimulation of transcription initiation. Thus, by blocking the negative feedback circuit, HMBA functions as a signaling enhancer of the NF-κB signaling pathway.

WIPI3 and WIPI4 β-propellers are scaffolds for LKB1-AMPK-TSC signalling circuits in the control of autophagy

PubMed Central

Bakula, Daniela; Müller, Amelie J.; Zuleger, Theresia; Takacs, Zsuzsanna; Franz-Wachtel, Mirita; Thost, Ann-Katrin; Brigger, Daniel; Tschan, Mario P.; Frickey, Tancred; Robenek, Horst; Macek, Boris; Proikas-Cezanne, Tassula

2017-01-01

Autophagy is controlled by AMPK and mTOR, both of which associate with ULK1 and control the production of phosphatidylinositol 3-phosphate (PtdIns3P), a prerequisite for autophagosome formation. Here we report that WIPI3 and WIPI4 scaffold the signal control of autophagy upstream of PtdIns3P production and have a role in the PtdIns3P effector function of WIPI1-WIPI2 at nascent autophagosomes. In response to LKB1-mediated AMPK stimulation, WIPI4-ATG2 is released from a WIPI4-ATG2/AMPK-ULK1 complex and translocates to nascent autophagosomes, controlling their size, to which WIPI3, in complex with FIP200, also contributes. Upstream, WIPI3 associates with AMPK-activated TSC complex at lysosomes, regulating mTOR. Our WIPI interactome analysis reveals the scaffold functions of WIPI proteins interconnecting autophagy signal control and autophagosome formation. Our functional kinase screen uncovers a novel regulatory link between LKB1-mediated AMPK stimulation that produces a direct signal via WIPI4, and we show that the AMPK-related kinases NUAK2 and BRSK2 regulate autophagy through WIPI4. PMID:28561066

GATING CIRCUITS

DOEpatents

Merrill, L.C.

1958-10-14

Control circuits for vacuum tubes are described, and a binary counter having an improved trigger circuit is reported. The salient feature of the binary counter is the application of the input signal to the cathode of each of two vacuum tubes through separate capacitors and the connection of each cathode to ground through separate diodes. The control of the binary counter is achieved in this manner without special pulse shaping of the input signal. A further advantage of the circuit is the simplicity and minimum nuruber of components required, making its use particularly desirable in computer machines.

MET Receptor Tyrosine Kinase as an Autism Genetic Risk Factor

PubMed Central

Peng, Yun; Huentelman, Matthew; Smith, Christopher; Qiu, Shenfeng

2014-01-01

In this chapter, we will briefly discuss recent literature on the role of MET receptor tyrosine kinase (RTK) in brain development and how perturbation of MET signaling may alter normal neurodevelopmental outcomes. Recent human genetic studies have established MET as a risk factor for autism, and the molecular and cellular underpinnings of this genetic risk are only beginning to emerge from obscurity. Unlike many autism risk genes that encode synaptic proteins, the spatial and temporal expression pattern of MET RTK indicates this signaling system is ideally situated to regulate neuronal growth, functional maturation, and establishment of functional brain circuits, particularly in those brain structures involved in higher levels of cognition, social skills, and executive functions. PMID:24290385

49 CFR 236.5 - Design of control circuits on closed circuit principle.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Design of control circuits on closed circuit... THE INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Rules and Instructions: All Systems General § 236.5 Design of control circuits on...

49 CFR 236.5 - Design of control circuits on closed circuit principle.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Design of control circuits on closed circuit... THE INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Rules and Instructions: All Systems General § 236.5 Design of control circuits on...

49 CFR 236.5 - Design of control circuits on closed circuit principle.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Design of control circuits on closed circuit... THE INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Rules and Instructions: All Systems General § 236.5 Design of control circuits on...

49 CFR 236.5 - Design of control circuits on closed circuit principle.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Design of control circuits on closed circuit... THE INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Rules and Instructions: All Systems General § 236.5 Design of control circuits on...

49 CFR 236.5 - Design of control circuits on closed circuit principle.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Design of control circuits on closed circuit... THE INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Rules and Instructions: All Systems General § 236.5 Design of control circuits on...

Hybrid ECG signal conditioner

NASA Technical Reports Server (NTRS)

Rinard, G. A.; Steffen, D. A.; Sturm, R. E.

1979-01-01

Circuit with high common-mode rejection has ability to filter and amplify accepted analog electrocardiogram (ECG) signals of varying amplitude, shape, and polarity. In addition, low power circuit develops standardized pulses that can be counted and averaged by heart/breath rate processor.

Apparatus for Controlling Low Power Voltages in Space Based Processing Systems

NASA Technical Reports Server (NTRS)

Petrick, David J. (Inventor)

2017-01-01

A low power voltage control circuit for use in space missions includes a switching device coupled between an input voltage and an output voltage. The switching device includes a control input coupled to an enable signal, wherein the control input is configured to selectively turn the output voltage on or off based at least in part on the enable signal. A current monitoring circuit is coupled to the output voltage and configured to produce a trip signal, wherein the trip signal is active when a load current flowing through the switching device is determined to exceed a predetermined threshold and is inactive otherwise. The power voltage control circuit is constructed of space qualified components.

Analog bus driver and multiplexer

NASA Technical Reports Server (NTRS)

Pain, Bedabrata (Inventor); Hancock, Bruce (Inventor); Cunningham, Thomas J. (Inventor)

2012-01-01

For a source-follower signal chain, the ohmic drop in the selection switch causes unacceptable voltage offset, non-linearity, and reduced small signal gain. For an op amp signal chain, the required bias current and the output noise rises rapidly with increasing the array format due to a rapid increase in the effective capacitance caused by the Miller effect boosting up the contribution of the bus capacitance. A new switched source-follower signal chain circuit overcomes limitations of existing op-amp based or source follower based circuits used in column multiplexers and data readout. This will improve performance of CMOS imagers, and focal plane read-out integrated circuits for detectors of infrared or ultraviolet light.

Current Regulator For Sodium-Vapor Lamps

NASA Technical Reports Server (NTRS)

Mclyman, W. T.

1989-01-01

Regulating circuit maintains nearly-constant alternating current in sodium-vapor lamp. Regulator part of dc-to-ac inverter circuit used to supply power to street lamp from battery charged by solar-cell array.

48 CFR 225.7006 - Restriction on air circuit breakers for naval vessels.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Restriction on air circuit breakers for naval vessels. 225.7006 Section 225.7006 Federal Acquisition Regulations System DEFENSE... on air circuit breakers for naval vessels. ...

48 CFR 225.7006 - Restriction on air circuit breakers for naval vessels.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Restriction on air circuit breakers for naval vessels. 225.7006 Section 225.7006 Federal Acquisition Regulations System DEFENSE... on air circuit breakers for naval vessels. ...

Dissecting the Signaling Mechanisms Underlying Recognition and Preference of Food Odors

PubMed Central

Harris, Gareth; Shen, Yu; Ha, Heonick; Donato, Alessandra; Wallis, Samuel; Zhang, Xiaodong

2014-01-01

Food is critical for survival. Many animals, including the nematode Caenorhabditis elegans, use sensorimotor systems to detect and locate preferred food sources. However, the signaling mechanisms underlying food-choice behaviors are poorly understood. Here, we characterize the molecular signaling that regulates recognition and preference between different food odors in C. elegans. We show that the major olfactory sensory neurons, AWB and AWC, play essential roles in this behavior. A canonical Gα-protein, together with guanylate cyclases and cGMP-gated channels, is needed for the recognition of food odors. The food-odor-evoked signal is transmitted via glutamatergic neurotransmission from AWC and through AMPA and kainate-like glutamate receptor subunits. In contrast, peptidergic signaling is required to generate preference between different food odors while being dispensable for the recognition of the odors. We show that this regulation is achieved by the neuropeptide NLP-9 produced in AWB, which acts with its putative receptor NPR-18, and by the neuropeptide NLP-1 produced in AWC. In addition, another set of sensory neurons inhibits food-odor preference. These mechanistic logics, together with a previously mapped neural circuit underlying food-odor preference, provide a functional network linking sensory response, transduction, and downstream receptors to process complex olfactory information and generate the appropriate behavioral decision essential for survival. PMID:25009271

Seeing through the smoke: Human and animal studies of cannabis use and endocannabinoid signalling in corticolimbic networks.

PubMed

Silveira, Mason M; Arnold, Jonathon C; Laviolette, Steven R; Hillard, Cecilia J; Celorrio, Marta; Aymerich, María S; Adams, Wendy K

2017-05-01

Public opinion surrounding the recreational use and therapeutic potential of cannabis is shifting. This review describes new work examining the behavioural and neural effects of cannabis and the endocannabinoid system, highlighting key regions within corticolimbic brain circuits. First, we consider the role of human genetic factors and cannabis strain chemotypic differences in contributing to interindividual variation in the response to cannabinoids, such as THC, and review studies demonstrating that THC-induced impairments in decision-making processes are mediated by actions at prefrontal CB 1 receptors. We further describe evidence that signalling through prefrontal or ventral hippocampal CB 1 receptors modulates mesolimbic dopamine activity, aberrations of which may contribute to emotional processing deficits in schizophrenia. Lastly, we review studies suggesting that endocannabinoid tone in the amygdala is a critical regulator of anxiety, and report new data showing that FAAH activity is integral to this response. Together, these findings underscore the importance of cannabinoid signalling in the regulation of cognitive and affective behaviours, and encourage further research given their social, political, and therapeutic implications. Copyright © 2016 Elsevier Ltd. All rights reserved.

Seeing through the smoke: human and animal studies of cannabis use and endocannabinoid signalling in corticolimbic networks

PubMed Central

Silveira, Mason M.; Arnold, Jonathon C.; Laviolette, Steven R.; Hillard, Cecilia J.; Celorrio, Marta; Aymerich, María S.; Adams, Wendy K.

2016-01-01

Public opinion surrounding the recreational use and therapeutic potential of cannabis is shifting. This review describes new work examining the behavioural and neural effects of cannabis and the endocannabinoid system, highlighting key regions within corticolimbic brain circuits. First, we consider the role of human genetic factors and cannabis strain chemotypic differences in contributing to interindividual variation in the response to cannabinoids, such as THC, and review studies demonstrating that THC-induced impairments in decision-making processes are mediated by actions at prefrontal CB1 receptors. We further describe evidence that signalling through prefrontal or ventral hippocampal CB1 receptors modulates mesolimbic dopamine activity, aberrations of which may contribute to emotional processing deficits in schizophrenia. Lastly, we review studies suggesting that endocannabinoid tone in the amygdala is a critical regulator of anxiety, and report new data showing that FAAH activity is integral to this response. Together, these findings underscore the importance of cannabinoid signalling in the regulation of cognitive and affective behaviours, and encourage further research given their social, political, and therapeutic implications. PMID:27639448

The constant current loop - A new paradigm for resistance signal conditioning

NASA Astrophysics Data System (ADS)

Anderson, Karl F.

A practical single constant current loop circuit for the signal conditioning of variable-resistance transducers has been synthesized, analyzed, and demonstrated. The strain gage and the resistance temperature device are examples of variable-resistance sensors. Lead wires connect variable-resistance sensors to remotely located signal-conditioning hardware. The presence of lead wires in the conventional Wheatstone bridge signal-conditioning circuit introduces undesired effects that reduce the quality of the data from the remote sensors. A practical approach is presented for suppressing essentially all lead wire resistance effects while indicating only the change in resistance value. An adaptation of the current loop circuit is presented that simultaneously provides an output signal voltage directly proportional to transducer resistance change and provides temperature information that is unaffected by transducer and lead wire resistance variations.

The constant current loop - A new paradigm for resistance signal conditioning

NASA Technical Reports Server (NTRS)

Anderson, Karl F.

1993-01-01

A practical single constant current loop circuit for the signal conditioning of variable-resistance transducers has been synthesized, analyzed, and demonstrated. The strain gage and the resistance temperature device are examples of variable-resistance sensors. Lead wires connect variable-resistance sensors to remotely located signal-conditioning hardware. The presence of lead wires in the conventional Wheatstone bridge signal-conditioning circuit introduces undesired effects that reduce the quality of the data from the remote sensors. A practical approach is presented for suppressing essentially all lead wire resistance effects while indicating only the change in resistance value. An adaptation of the current loop circuit is presented that simultaneously provides an output signal voltage directly proportional to transducer resistance change and provides temperature information that is unaffected by transducer and lead wire resistance variations.

Enabling complex genetic circuits to respond to extrinsic environmental signals.

PubMed

Hoynes-O'Connor, Allison; Shopera, Tatenda; Hinman, Kristina; Creamer, John Philip; Moon, Tae Seok

2017-07-01

Genetic circuits have the potential to improve a broad range of metabolic engineering processes and address a variety of medical and environmental challenges. However, in order to engineer genetic circuits that can meet the needs of these real-world applications, genetic sensors that respond to relevant extrinsic and intrinsic signals must be implemented in complex genetic circuits. In this work, we construct the first AND and NAND gates that respond to temperature and pH, two signals that have relevance in a variety of real-world applications. A previously identified pH-responsive promoter and a temperature-responsive promoter were extracted from the E. coli genome, characterized, and modified to suit the needs of the genetic circuits. These promoters were combined with components of the type III secretion system in Salmonella typhimurium and used to construct a set of AND gates with up to 23-fold change. Next, an antisense RNA was integrated into the circuit architecture to invert the logic of the AND gate and generate a set of NAND gates with up to 1168-fold change. These circuits provide the first demonstration of complex pH- and temperature-responsive genetic circuits, and lay the groundwork for the use of similar circuits in real-world applications. Biotechnol. Bioeng. 2017;114: 1626-1631. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Age–dependent regulation of synaptic connections by dopamine D2 receptors

PubMed Central

Jia, Jie–Min; Zhao, Jun; Hu, Zhonghua; Lindberg, Daniel; Li, Zheng

2013-01-01

Dopamine D2 receptors (D2R) are G protein–coupled receptors that modulate synaptic transmission and play an important role in various brain functions including affect learning and working memory. Abnormal D2R signaling has been implicated in psychiatric disorders such as schizophrenia. Here we report a new function of D2R in dendritic spine morphogenesis. Activation of D2R reduces spine number via GluN2B– and cAMP–dependent mechanisms in mice. Notably, this regulation takes place only during adolescence. During this period, D2R overactivation caused by mutations in the schizophrenia–risk–gene dysbindin leads to spine deficiency, dysconnectivity within the entorhinal–hippocampal circuit and impairment of spatial working memory. Notably, these defects can be ameliorated by D2R blockers administered during adolescence. These findings uncover a novel age–dependent function of D2R in spine development, provide evidence that D2R dysfunction during adolescence impairs neuronal circuits and working memory, and suggest that adolescent interventions of aberrant D2R activity protect against cognitive impairment. PMID:24121738

Overload protection for switching regulators

NASA Technical Reports Server (NTRS)

Lachochi, E.

1980-01-01

Circuit protects all output lines of switching regulator against overloads without requiring current sensors on every line. If overload is sensed, device short circuits bias on switching transistor so that power is rapidly cut off from loads. Circuit also includes delay network to inhibit erroneous operation during startup.

Evolutionary Analysis of DELLA-Associated Transcriptional Networks.

PubMed

Briones-Moreno, Asier; Hernández-García, Jorge; Vargas-Chávez, Carlos; Romero-Campero, Francisco J; Romero, José M; Valverde, Federico; Blázquez, Miguel A

2017-01-01

DELLA proteins are transcriptional regulators present in all land plants which have been shown to modulate the activity of over 100 transcription factors in Arabidopsis, involved in multiple physiological and developmental processes. It has been proposed that DELLAs transduce environmental information to pre-wired transcriptional circuits because their stability is regulated by gibberellins (GAs), whose homeostasis largely depends on environmental signals. The ability of GAs to promote DELLA degradation coincides with the origin of vascular plants, but the presence of DELLAs in other land plants poses at least two questions: what regulatory properties have DELLAs provided to the behavior of transcriptional networks in land plants, and how has the recruitment of DELLAs by GA signaling affected this regulation. To address these issues, we have constructed gene co-expression networks of four different organisms within the green lineage with different properties regarding DELLAs: Arabidopsis thaliana and Solanum lycopersicum (both with GA-regulated DELLA proteins), Physcomitrella patens (with GA-independent DELLA proteins) and Chlamydomonas reinhardtii (a green alga without DELLA), and we have examined the relative evolution of the subnetworks containing the potential DELLA-dependent transcriptomes. Network analysis indicates a relative increase in parameters associated with the degree of interconnectivity in the DELLA-associated subnetworks of land plants, with a stronger effect in species with GA-regulated DELLA proteins. These results suggest that DELLAs may have played a role in the coordination of multiple transcriptional programs along evolution, and the function of DELLAs as regulatory 'hubs' became further consolidated after their recruitment by GA signaling in higher plants.

49 CFR 236.2 - Grounds.

Code of Federal Regulations, 2011 CFR

2011-10-01

... circuit, except circuits which include any track rail and except the common return wires of single-wire, single-break, signal control circuits using a grounded common, and alternating current power distribution...

49 CFR 236.2 - Grounds.

Code of Federal Regulations, 2013 CFR

2013-10-01

... circuit, except circuits which include any track rail and except the common return wires of single-wire, single-break, signal control circuits using a grounded common, and alternating current power distribution...

49 CFR 236.2 - Grounds.

Code of Federal Regulations, 2012 CFR

2012-10-01

... circuit, except circuits which include any track rail and except the common return wires of single-wire, single-break, signal control circuits using a grounded common, and alternating current power distribution...

Central nervous system regulation of intestinal lipid and lipoprotein metabolism.

PubMed

Farr, Sarah; Taher, Jennifer; Adeli, Khosrow

2016-02-01

In response to nutrient availability, the small intestine and brain closely communicate to modulate energy homeostasis and metabolism. The gut-brain axis involves complex nutrient sensing mechanisms and an integration of neuronal and hormonal signaling. This review summarizes recent evidence implicating the gut-brain axis in regulating lipoprotein metabolism, with potential implications for the dyslipidemia of insulin resistant states. The intestine and brain possess distinct mechanisms for sensing lipid availability, which triggers subsequent regulation of feeding, glucose homeostasis, and adipose tissue metabolism. More recently, central receptors, neuropeptides, and gut hormones that communicate with the brain have been shown to modulate hepatic and intestinal lipoprotein metabolism via parasympathetic and sympathetic signaling. Gut-derived glucagon-like peptides appear to be particularly important in modulating the intestinal secretion of chylomicron particles via a novel brain-gut axis. Dysregulation of these pathways may contribute to postprandial diabetic dyslipidemia. Emerging evidence implicates the central and enteric nervous systems in controlling many aspects of lipid and lipoprotein metabolism. Bidirectional communication between the gut and brain involving neuronal pathways and gut peptides is critical for regulating feeding and metabolism, and forms a neuroendocrine circuit to modulate dietary fat absorption and intestinal production of atherogenic chylomicron particles.

Photo-Spectrometer Realized In A Standard Cmos Ic Process

DOEpatents

Simpson, Michael L.; Ericson, M. Nance; Dress, William B.; Jellison, Gerald E.; Sitter, Jr., David N.; Wintenberg, Alan L.

1999-10-12

A spectrometer, comprises: a semiconductor having a silicon substrate, the substrate having integrally formed thereon a plurality of layers forming photo diodes, each of the photo diodes having an independent spectral response to an input spectra within a spectral range of the semiconductor and each of the photo diodes formed only from at least one of the plurality of layers of the semiconductor above the substrate; and, a signal processing circuit for modifying signals from the photo diodes with respective weights, the weighted signals being representative of a specific spectral response. The photo diodes have different junction depths and different polycrystalline silicon and oxide coverings. The signal processing circuit applies the respective weights and sums the weighted signals. In a corresponding method, a spectrometer is manufactured by manipulating only the standard masks, materials and fabrication steps of standard semiconductor processing, and integrating the spectrometer with a signal processing circuit.

Automatic control of clock duty cycle

NASA Technical Reports Server (NTRS)

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

2010-01-01

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

Physiological controls of large‐scale patterning in planarian regeneration: a molecular and computational perspective on growth and form

PubMed Central

Durant, Fallon; Lobo, Daniel; Hammelman, Jennifer

2016-01-01

Abstract Planaria are complex metazoans that repair damage to their bodies and cease remodeling when a correct anatomy has been achieved. This model system offers a unique opportunity to understand how large‐scale anatomical homeostasis emerges from the activities of individual cells. Much progress has been made on the molecular genetics of stem cell activity in planaria. However, recent data also indicate that the global pattern is regulated by physiological circuits composed of ionic and neurotransmitter signaling. Here, we overview the multi‐scale problem of understanding pattern regulation in planaria, with specific focus on bioelectric signaling via ion channels and gap junctions (electrical synapses), and computational efforts to extract explanatory models from functional and molecular data on regeneration. We present a perspective that interprets results in this fascinating field using concepts from dynamical systems theory and computational neuroscience. Serving as a tractable nexus between genetic, physiological, and computational approaches to pattern regulation, planarian pattern homeostasis harbors many deep insights for regenerative medicine, evolutionary biology, and engineering. PMID:27499881

Effects of Pregnane Glycosides on Food Intake Depend on Stimulation of the Melanocortin Pathway and BDNF in an Animal Model

PubMed Central

Komarnytsky, Slavko; Esposito, Debora; Rathinasabapathy, Thirumurugan; Poulev, Alexander; Raskin, Ilya

2013-01-01

Pregnane glycosides appear to modulate food intake by possibly affecting the hypothalamic feeding circuits; however, the mechanisms of the appetite-regulating effect of pregnane glycosides remain obscure. Here, we show that pregnane glycoside-enriched extracts from swamp milkweed Asclepias incarnata at 25–100 mg/kg daily attenuated food intake (up to 47.1 ± 8.5% less than controls) and body weight gain in rats (10% for males and 9% for females, respectively) by activating melanocortin signaling and inhibiting gastric emptying. The major milkweed pregnane glycoside, ikemagenin, exerted its appetite-regulating effect by decreasing levels of agouti-related protein (0.6-fold) but not NPY satiety peptides. Ikemagenin treatment also increased secretion of brain-derived neurotropic factor (BDNF) downstream of melanocortin receptors in the hypothalamus (1.4-fold) and in the C6 rat glioma cell culture in vitro (up to 6-fold). These results support the multimodal effects of pregnane glycosides on feeding regulation, which depends on the activity of the melanocortin signaling pathway and BDNF. PMID:23308358

Effects of pregnane glycosides on food intake depend on stimulation of the melanocortin pathway and BDNF in an animal model.

PubMed

Komarnytsky, Slavko; Esposito, Debora; Rathinasabapathy, Thirumurugan; Poulev, Alexander; Raskin, Ilya

2013-02-27

Pregnane glycosides appear to modulate food intake by possibly affecting the hypothalamic feeding circuits; however, the mechanisms of the appetite-regulating effect of pregnane glycosides remain obscure. Here, we show that pregnane glycoside-enriched extracts from swamp milkweed Asclepias incarnata at 25-100 mg/kg daily attenuated food intake (up to 47.1 ± 8.5% less than controls) and body weight gain in rats (10% for males and 9% for females, respectively) by activating melanocortin signaling and inhibiting gastric emptying. The major milkweed pregnane glycoside, ikemagenin, exerted its appetite-regulating effect by decreasing levels of agouti-related protein (0.6-fold) but not NPY satiety peptides. Ikemagenin treatment also increased secretion of brain-derived neurotropic factor (BDNF) downstream of melanocortin receptors in the hypothalamus (1.4-fold) and in the C6 rat glioma cell culture in vitro (up to 6-fold). These results support the multimodal effects of pregnane glycosides on feeding regulation, which depends on the activity of the melanocortin signaling pathway and BDNF.

Immunity in Drosophila melanogaster--from microbial recognition to whole-organism physiology.

PubMed

Buchon, Nicolas; Silverman, Neal; Cherry, Sara

2014-12-01

Since the discovery of antimicrobial peptide responses 40 years ago, the fruit fly Drosophila melanogaster has proven to be a powerful model for the study of innate immunity. Early work focused on innate immune mechanisms of microbial recognition and subsequent nuclear factor-κB signal transduction. More recently, D. melanogaster has been used to understand how the immune response is regulated and coordinated at the level of the whole organism. For example, researchers have used this model in studies investigating interactions between the microbiota and the immune system at barrier epithelial surfaces that ensure proper nutritional and immune homeostasis both locally and systemically. In addition, studies in D. melanogaster have been pivotal in uncovering how the immune response is regulated by both endocrine and metabolic signalling systems, and how the immune response modifies these systems as part of a homeostatic circuit. In this Review, we briefly summarize microbial recognition and antiviral immunity in D. melanogaster, and we highlight recent studies that have explored the effects of organism-wide regulation of the immune response and, conversely, the effects of the immune response on organism physiology.

Apparatus for and method of testing an electrical ground fault circuit interrupt device

DOEpatents

Andrews, L.B.

1998-08-18

An apparatus for testing a ground fault circuit interrupt device includes a processor, an input device connected to the processor for receiving input from an operator, a storage media connected to the processor for storing test data, an output device connected to the processor for outputting information corresponding to the test data to the operator, and a calibrated variable load circuit connected between the processor and the ground fault circuit interrupt device. The ground fault circuit interrupt device is configured to trip a corresponding circuit breaker. The processor is configured to receive signals from the calibrated variable load circuit and to process the signals to determine a trip threshold current and/or a trip time. A method of testing the ground fault circuit interrupt device includes a first step of providing an identification for the ground fault circuit interrupt device. Test data is then recorded in accordance with the identification. By comparing test data from an initial test with test data from a subsequent test, a trend of performance for the ground fault circuit interrupt device is determined. 17 figs.

Apparatus for and method of testing an electrical ground fault circuit interrupt device

DOEpatents

Andrews, Lowell B.

1998-01-01

An apparatus for testing a ground fault circuit interrupt device includes a processor, an input device connected to the processor for receiving input from an operator, a storage media connected to the processor for storing test data, an output device connected to the processor for outputting information corresponding to the test data to the operator, and a calibrated variable load circuit connected between the processor and the ground fault circuit interrupt device. The ground fault circuit interrupt device is configured to trip a corresponding circuit breaker. The processor is configured to receive signals from the calibrated variable load circuit and to process the signals to determine a trip threshold current and/or a trip time. A method of testing the ground fault circuit interrupt device includes a first step of providing an identification for the ground fault circuit interrupt device. Test data is then recorded in accordance with the identification. By comparing test data from an initial test with test data from a subsequent test, a trend of performance for the ground fault circuit interrupt device is determined.

Microscale autonomous sensor and communications module

DOEpatents

Okandan, Murat; Nielson, Gregory N

2014-03-25

Various technologies pertaining to a microscale autonomous sensor and communications module are described herein. Such a module includes a sensor that generates a sensor signal that is indicative of an environmental parameter. An integrated circuit receives the sensor signal and generates an output signal based at least in part upon the sensor signal. An optical emitter receives the output signal and generates an optical signal as a function of the output signal. An energy storage device is configured to provide power to at least the integrated circuit and the optical emitter, and wherein the module has a relatively small diameter and thickness.

49 CFR 236.60 - Switch shunting circuit; use restricted.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Rules and... circuit shall not be hereafter installed, except where tract or control circuit is opened by the circuit controller. [49 FR 3384, Jan. 26, 1984] Wires and Cables ...

49 CFR 236.60 - Switch shunting circuit; use restricted.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Rules and... circuit shall not be hereafter installed, except where tract or control circuit is opened by the circuit controller. [49 FR 3384, Jan. 26, 1984] Wires and Cables ...

49 CFR 236.60 - Switch shunting circuit; use restricted.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Rules and... circuit shall not be hereafter installed, except where tract or control circuit is opened by the circuit controller. [49 FR 3384, Jan. 26, 1984] Wires and Cables ...

49 CFR 236.60 - Switch shunting circuit; use restricted.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Rules and... circuit shall not be hereafter installed, except where tract or control circuit is opened by the circuit controller. [49 FR 3384, Jan. 26, 1984] Wires and Cables ...

49 CFR 236.60 - Switch shunting circuit; use restricted.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Rules and... circuit shall not be hereafter installed, except where tract or control circuit is opened by the circuit controller. [49 FR 3384, Jan. 26, 1984] Wires and Cables ...

Gated integrator with signal baseline subtraction

DOEpatents

Wang, X.

1996-12-17

An ultrafast, high precision gated integrator includes an opamp having differential inputs. A signal to be integrated is applied to one of the differential inputs through a first input network, and a signal indicative of the DC offset component of the signal to be integrated is applied to the other of the differential inputs through a second input network. A pair of electronic switches in the first and second input networks define an integrating period when they are closed. The first and second input networks are substantially symmetrically constructed of matched components so that error components introduced by the electronic switches appear symmetrically in both input circuits and, hence, are nullified by the common mode rejection of the integrating opamp. The signal indicative of the DC offset component is provided by a sample and hold circuit actuated as the integrating period begins. The symmetrical configuration of the integrating circuit improves accuracy and speed by balancing out common mode errors, by permitting the use of high speed switching elements and high speed opamps and by permitting the use of a small integrating time constant. The sample and hold circuit substantially eliminates the error caused by the input signal baseline offset during a single integrating window. 5 figs.

Gated integrator with signal baseline subtraction

DOEpatents

Wang, Xucheng

1996-01-01

An ultrafast, high precision gated integrator includes an opamp having differential inputs. A signal to be integrated is applied to one of the differential inputs through a first input network, and a signal indicative of the DC offset component of the signal to be integrated is applied to the other of the differential inputs through a second input network. A pair of electronic switches in the first and second input networks define an integrating period when they are closed. The first and second input networks are substantially symmetrically constructed of matched components so that error components introduced by the electronic switches appear symmetrically in both input circuits and, hence, are nullified by the common mode rejection of the integrating opamp. The signal indicative of the DC offset component is provided by a sample and hold circuit actuated as the integrating period begins. The symmetrical configuration of the integrating circuit improves accuracy and speed by balancing out common mode errors, by permitting the use of high speed switching elements and high speed opamps and by permitting the use of a small integrating time constant. The sample and hold circuit substantially eliminates the error caused by the input signal baseline offset during a single integrating window.

Signal transduction meets vesicle traffic: the software and hardware of GLUT4 translocation.

PubMed

Klip, Amira; Sun, Yi; Chiu, Tim Ting; Foley, Kevin P

2014-05-15

Skeletal muscle is the major tissue disposing of dietary glucose, a function regulated by insulin-elicited signals that impart mobilization of GLUT4 glucose transporters to the plasma membrane. This phenomenon, also central to adipocyte biology, has been the subject of intense and productive research for decades. We focus on muscle cell studies scrutinizing insulin signals and vesicle traffic in a spatiotemporal manner. Using the analogy of an integrated circuit to approach the intersection between signal transduction and vesicle mobilization, we identify signaling relays ("software") that engage structural/mechanical elements ("hardware") to enact the rapid mobilization and incorporation of GLUT4 into the cell surface. We emphasize how insulin signal transduction switches from tyrosine through lipid and serine phosphorylation down to activation of small G proteins of the Rab and Rho families, describe key negative regulation step of Rab GTPases through the GTPase-activating protein activity of the Akt substrate of 160 kDa (AS160), and focus on the mechanical effectors engaged by Rabs 8A and 10 (the molecular motor myosin Va), and the Rho GTPase Rac1 (actin filament branching and severing through Arp2/3 and cofilin). Finally, we illustrate how actin filaments interact with myosin 1c and α-Actinin4 to promote vesicle tethering as preamble to fusion with the membrane. Copyright © 2014 the American Physiological Society.

Hardware Design and Implementation of a Wavelet De-Noising Procedure for Medical Signal Preprocessing

PubMed Central

Chen, Szi-Wen; Chen, Yuan-Ho

2015-01-01

In this paper, a discrete wavelet transform (DWT) based de-noising with its applications into the noise reduction for medical signal preprocessing is introduced. This work focuses on the hardware realization of a real-time wavelet de-noising procedure. The proposed de-noising circuit mainly consists of three modules: a DWT, a thresholding, and an inverse DWT (IDWT) modular circuits. We also proposed a novel adaptive thresholding scheme and incorporated it into our wavelet de-noising procedure. Performance was then evaluated on both the architectural designs of the software and. In addition, the de-noising circuit was also implemented by downloading the Verilog codes to a field programmable gate array (FPGA) based platform so that its ability in noise reduction may be further validated in actual practice. Simulation experiment results produced by applying a set of simulated noise-contaminated electrocardiogram (ECG) signals into the de-noising circuit showed that the circuit could not only desirably meet the requirement of real-time processing, but also achieve satisfactory performance for noise reduction, while the sharp features of the ECG signals can be well preserved. The proposed de-noising circuit was further synthesized using the Synopsys Design Compiler with an Artisan Taiwan Semiconductor Manufacturing Company (TSMC, Hsinchu, Taiwan) 40 nm standard cell library. The integrated circuit (IC) synthesis simulation results showed that the proposed design can achieve a clock frequency of 200 MHz and the power consumption was only 17.4 mW, when operated at 200 MHz. PMID:26501290

Parallel basal ganglia circuits for decision making.

PubMed

Hikosaka, Okihide; Ghazizadeh, Ali; Griggs, Whitney; Amita, Hidetoshi

2018-03-01

The basal ganglia control body movements, mainly, based on their values. Critical for this mechanism is dopamine neurons, which sends unpredicted value signals, mainly, to the striatum. This mechanism enables animals to change their behaviors flexibly, eventually choosing a valuable behavior. However, this may not be the best behavior, because the flexible choice is focused on recent, and, therefore, limited, experiences (i.e., short-term memories). Our old and recent studies suggest that the basal ganglia contain separate circuits that process value signals in a completely different manner. They are insensitive to recent changes in value, yet gradually accumulate the value of each behavior (i.e., movement or object choice). These stable circuits eventually encode values of many behaviors and then retain the value signals for a long time (i.e., long-term memories). They are innervated by a separate group of dopamine neurons that retain value signals, even when no reward is predicted. Importantly, the stable circuits can control motor behaviors (e.g., hand or eye) quickly and precisely, which allows animals to automatically acquire valuable outcomes based on historical life experiences. These behaviors would be called 'skills', which are crucial for survival. The stable circuits are localized in the posterior part of the basal ganglia, separately from the flexible circuits located in the anterior part. To summarize, the flexible and stable circuits in the basal ganglia, working together but independently, enable animals (and humans) to reach valuable goals in various contexts.

Hardware design and implementation of a wavelet de-noising procedure for medical signal preprocessing.

PubMed

Chen, Szi-Wen; Chen, Yuan-Ho

2015-10-16

In this paper, a discrete wavelet transform (DWT) based de-noising with its applications into the noise reduction for medical signal preprocessing is introduced. This work focuses on the hardware realization of a real-time wavelet de-noising procedure. The proposed de-noising circuit mainly consists of three modules: a DWT, a thresholding, and an inverse DWT (IDWT) modular circuits. We also proposed a novel adaptive thresholding scheme and incorporated it into our wavelet de-noising procedure. Performance was then evaluated on both the architectural designs of the software and. In addition, the de-noising circuit was also implemented by downloading the Verilog codes to a field programmable gate array (FPGA) based platform so that its ability in noise reduction may be further validated in actual practice. Simulation experiment results produced by applying a set of simulated noise-contaminated electrocardiogram (ECG) signals into the de-noising circuit showed that the circuit could not only desirably meet the requirement of real-time processing, but also achieve satisfactory performance for noise reduction, while the sharp features of the ECG signals can be well preserved. The proposed de-noising circuit was further synthesized using the Synopsys Design Compiler with an Artisan Taiwan Semiconductor Manufacturing Company (TSMC, Hsinchu, Taiwan) 40 nm standard cell library. The integrated circuit (IC) synthesis simulation results showed that the proposed design can achieve a clock frequency of 200 MHz and the power consumption was only 17.4 mW, when operated at 200 MHz.

Conditions and constraints for astrocyte calcium signaling in the hippocampal mossy fiber pathway

PubMed Central

Haustein, Martin D.; Kracun, Sebastian; Lu, Xiao-Hong; Shih, Tiffany; Jackson-Weaver, Olan; Tong, Xiaoping; Xu, Ji; Yang, X. William; O'Dell, Thomas J.; Marvin, Jonathan S.; Ellisman, Mark H.; Bushong, Eric A.; Looger, Loren L.; Khakh, Baljit S.

2014-01-01

Summary The spatiotemporal activities of astrocyte Ca2+ signaling in mature neuronal circuits remain unclear. We used genetically encoded Ca2+ and glutamate indicators as well as pharmacogenetic and electrical control of neurotransmitter release to explore astrocyte activity in the hippocampal mossy fiber pathway. Our data revealed numerous localised spontaneous Ca2+ signals in astrocyte branches and territories, but these were not driven by neuronal activity or glutamate. Moreover, evoked astrocyte Ca2+ signaling changed linearly with the number of mossy fiber action potentials. Under these settings astrocyte responses were global, suppressed by neurotransmitter clearance and mediated by glutamate and GABA. Thus, astrocyte engagement in the fully developed mossy fiber pathway was slow and territorial, contrary to that frequently proposed for astrocytes within microcircuits. We show that astrocyte Ca2+ signaling functionally segregates large volumes of neuropil and that these transients are not suited for responding to, or regulating, single synapses in the mossy fiber pathway. PMID:24742463

Functional PDF Signaling in the Drosophila Circadian Neural Circuit Is Gated by Ral A-Dependent Modulation.

PubMed

Klose, Markus; Duvall, Laura; Li, Weihua; Liang, Xitong; Ren, Chi; Steinbach, Joe Henry; Taghert, Paul H

2016-05-18

The neuropeptide PDF promotes the normal sequencing of circadian behavioral rhythms in Drosophila, but its signaling mechanisms are not well understood. We report daily rhythmicity in responsiveness to PDF in critical pacemakers called small LNvs. There is a daily change in potency, as great as 10-fold higher, around dawn. The rhythm persists in constant darkness and does not require endogenous ligand (PDF) signaling or rhythmic receptor gene transcription. Furthermore, rhythmic responsiveness reflects the properties of the pacemaker cell type, not the receptor. Dopamine responsiveness also cycles, in phase with that of PDF, in the same pacemakers, but does not cycle in large LNv. The activity of RalA GTPase in s-LNv regulates PDF responsiveness and behavioral locomotor rhythms. Additionally, cell-autonomous PDF signaling reversed the circadian behavioral effects of lowered RalA activity. Thus, RalA activity confers high PDF responsiveness, providing a daily gate around the dawn hours to promote functional PDF signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

Functional PDF Signaling in the Drosophila Circadian Neural Circuit is Gated by Ral A-Dependent Modulation

PubMed Central

Liang, Xitong; Ren, Chi; Steinbach, Joe Henry; Taghert, Paul H.

2016-01-01

The neuropeptide PDF promotes the normal sequencing of circadian behavioral rhythms in Drosophila, but its signaling mechanisms are not well understood. We report daily rhythmicity in responsiveness to PDF in critical pacemakers called small LNvs. There is a daily change in potency, as great as 10-fold higher, around dawn. The rhythm persists in constant darkness, does not require endogenous ligand (PDF) signaling, or rhythmic receptor gene transcription. Furthermore, rhythmic responsiveness reflects the properties of the pacemaker cell type, not the receptor. Dopamine responsiveness also cycles, in phase with that of PDF, in the same pacemakers, but does not cycle in large LNv. The activity of RalA GTPase in s-LNv regulates PDF responsiveness and behavioral locomotor rhythms. Additional, cell autonomous PDF signaling reversed the circadian behavioral effects of lowered RalA activity. Thus RalA activity confers high PDF responsiveness, providing a daily gate around the dawn hours to promote functional PDF signaling. PMID:27161526

Loss of microRNA-7a2 induces hypogonadotropic hypogonadism and infertility

PubMed Central

Ahmed, Kashan; LaPierre, Mary P.; Denzler, Rémy; Yang, Yinjie; Rülicke, Thomas; Latreille, Mathieu

2017-01-01

MicroRNAs (miRNAs) are negative modulators of gene expression that fine-tune numerous biological processes. miRNA loss-of-function rarely results in highly penetrant phenotypes, but rather, influences cellular responses to physiologic and pathophysiologic stresses. Here, we have reported that a single member of the evolutionarily conserved miR-7 family, miR-7a2, is essential for normal pituitary development and hypothalamic-pituitary-gonadal (HPG) function in adulthood. Genetic deletion of mir-7a2 causes infertility, with low levels of gonadotropic and sex steroid hormones, small testes or ovaries, impaired spermatogenesis, and lack of ovulation in male and female mice, respectively. We found that miR-7a2 is highly expressed in the pituitary, where it suppresses golgi glycoprotein 1 (GLG1) expression and downstream bone morphogenetic protein 4 (BMP4) signaling and also reduces expression of the prostaglandin F2a receptor negative regulator (PTGFRN), an inhibitor of prostaglandin signaling and follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secretion. Our results reveal that miR-7a2 critically regulates sexual maturation and reproductive function by interconnecting miR-7 genomic circuits that regulate FSH and LH synthesis and secretion through their effects on pituitary prostaglandin and BMP4 signaling. PMID:28218624

Growth Factor-Activated Stem Cell Circuits and Stromal Signals Cooperatively Accelerate Non-Integrated iPSC Reprogramming of Human Myeloid Progenitors

PubMed Central

Park, Tea Soon; Huo, Jeffrey S.; Peters, Ann; Talbot, C. Conover; Verma, Karan; Zimmerlin, Ludovic; Kaplan, Ian M.; Zambidis, Elias T.

2012-01-01

Nonviral conversion of skin or blood cells into clinically useful human induced pluripotent stem cells (hiPSC) occurs in only rare fractions (∼0.001%–0.5%) of donor cells transfected with non-integrating reprogramming factors. Pluripotency induction of developmentally immature stem-progenitors is generally more efficient than differentiated somatic cell targets. However, the nature of augmented progenitor reprogramming remains obscure, and its potential has not been fully explored for improving the extremely slow pace of non-integrated reprogramming. Here, we report highly optimized four-factor reprogramming of lineage-committed cord blood (CB) myeloid progenitors with bulk efficiencies of ∼50% in purified episome-expressing cells. Lineage-committed CD33+CD45+CD34− myeloid cells and not primitive hematopoietic stem-progenitors were the main targets of a rapid and nearly complete non-integrated reprogramming. The efficient conversion of mature myeloid populations into NANOG+TRA-1-81+ hiPSC was mediated by synergies between hematopoietic growth factor (GF), stromal activation signals, and episomal Yamanaka factor expression. Using a modular bioinformatics approach, we demonstrated that efficient myeloid reprogramming correlated not to increased proliferation or endogenous Core factor expressions, but to poised expression of GF-activated transcriptional circuits that commonly regulate plasticity in both hematopoietic progenitors and embryonic stem cells (ESC). Factor-driven conversion of myeloid progenitors to a high-fidelity pluripotent state was further accelerated by soluble and contact-dependent stromal signals that included an implied and unexpected role for Toll receptor-NFκB signaling. These data provide a paradigm for understanding the augmented reprogramming capacity of somatic progenitors, and reveal that efficient induced pluripotency in other cell types may also require extrinsic activation of a molecular framework that commonly regulates self-renewal and differentiation in both hematopoietic progenitors and ESC. PMID:22905176

Activation of the sympathetic nervous system mediates hypophagic and anxiety-like effects of CB₁ receptor blockade.

PubMed

Bellocchio, Luigi; Soria-Gómez, Edgar; Quarta, Carmelo; Metna-Laurent, Mathilde; Cardinal, Pierre; Binder, Elke; Cannich, Astrid; Delamarre, Anna; Häring, Martin; Martín-Fontecha, Mar; Vega, David; Leste-Lasserre, Thierry; Bartsch, Dusan; Monory, Krisztina; Lutz, Beat; Chaouloff, Francis; Pagotto, Uberto; Guzman, Manuel; Cota, Daniela; Marsicano, Giovanni

2013-03-19

Complex interactions between periphery and the brain regulate food intake in mammals. Cannabinoid type-1 (CB1) receptor antagonists are potent hypophagic agents, but the sites where this acute action is exerted and the underlying mechanisms are not fully elucidated. To dissect the mechanisms underlying the hypophagic effect of CB1 receptor blockade, we combined the acute injection of the CB1 receptor antagonist rimonabant with the use of conditional CB1-knockout mice, as well as with pharmacological modulation of different central and peripheral circuits. Fasting/refeeding experiments revealed that CB1 receptor signaling in many specific brain neurons is dispensable for the acute hypophagic effects of rimonabant. CB1 receptor antagonist-induced hypophagia was fully abolished by peripheral blockade of β-adrenergic transmission, suggesting that this effect is mediated by increased activity of the sympathetic nervous system. Consistently, we found that rimonabant increases gastrointestinal metabolism via increased peripheral β-adrenergic receptor signaling in peripheral organs, including the gastrointestinal tract. Blockade of both visceral afferents and glutamatergic transmission in the nucleus tractus solitarii abolished rimonabant-induced hypophagia. Importantly, these mechanisms were specifically triggered by lipid-deprivation, revealing a nutrient-specific component acutely regulated by CB1 receptor blockade. Finally, peripheral blockade of sympathetic neurotransmission also blunted central effects of CB1 receptor blockade, such as fear responses and anxiety-like behaviors. These data demonstrate that, independently of their site of origin, important effects of CB1 receptor blockade are expressed via activation of peripheral sympathetic activity. Thus, CB1 receptors modulate bidirectional circuits between the periphery and the brain to regulate feeding and other behaviors.

Electrical performance characteristics of high power converters for space power applications

NASA Technical Reports Server (NTRS)

Stuart, Thomas A.; King, Roger J.

1989-01-01

The first goal of this project was to investigate various converters that would be suitable for processing electric power derived from a nuclear reactor. The implementation is indicated of a 20 kHz system that includes a source converter, a ballast converter, and a fixed frequency converter for generating the 20 kHz output. This system can be converted to dc simply by removing the fixed frequency converter. This present study emphasized the design and testing of the source and ballast converters. A push-pull current-fed (PPCF) design was selected for the source converter, and a 2.7 kW version of this was implemented using three 900 watt modules in parallel. The characteristic equation for two converters in parallel was derived, but this analysis did not yield any experimental methods for measuring relative stability. The three source modules were first tested individually and then in parallel as a 2.7 kW system. All tests proved to be satisfactory; the system was stable; efficiency and regulation were acceptable; and the system was fault tolerant. The design of a ballast-load converter, which was operated as a shunt regulator, was investigated. The proposed power circuit is suitable for use with BJTs because proportional base drive is easily implemented. A control circuit which minimizes switching frequency ripple and automatically bypasses a faulty shunt section was developed. A nonlinear state-space-averaged model of the shunt regulator was developed and shown to produce an accurate incremental (small-signal) dynamic model, even though the usual state-space-averaging assumptions were not met. The nonlinear model was also shown to be useful for large-signal dynamic simulation using PSpice.

Activation of the sympathetic nervous system mediates hypophagic and anxiety-like effects of CB1 receptor blockade

PubMed Central

Bellocchio, Luigi; Soria-Gómez, Edgar; Quarta, Carmelo; Metna-Laurent, Mathilde; Cardinal, Pierre; Binder, Elke; Cannich, Astrid; Delamarre, Anna; Häring, Martin; Martín-Fontecha, Mar; Vega, David; Leste-Lasserre, Thierry; Bartsch, Dusan; Monory, Krisztina; Lutz, Beat; Chaouloff, Francis; Pagotto, Uberto; Guzman, Manuel; Cota, Daniela; Marsicano, Giovanni

2013-01-01

Complex interactions between periphery and the brain regulate food intake in mammals. Cannabinoid type-1 (CB1) receptor antagonists are potent hypophagic agents, but the sites where this acute action is exerted and the underlying mechanisms are not fully elucidated. To dissect the mechanisms underlying the hypophagic effect of CB1 receptor blockade, we combined the acute injection of the CB1 receptor antagonist rimonabant with the use of conditional CB1-knockout mice, as well as with pharmacological modulation of different central and peripheral circuits. Fasting/refeeding experiments revealed that CB1 receptor signaling in many specific brain neurons is dispensable for the acute hypophagic effects of rimonabant. CB1 receptor antagonist-induced hypophagia was fully abolished by peripheral blockade of β-adrenergic transmission, suggesting that this effect is mediated by increased activity of the sympathetic nervous system. Consistently, we found that rimonabant increases gastrointestinal metabolism via increased peripheral β-adrenergic receptor signaling in peripheral organs, including the gastrointestinal tract. Blockade of both visceral afferents and glutamatergic transmission in the nucleus tractus solitarii abolished rimonabant-induced hypophagia. Importantly, these mechanisms were specifically triggered by lipid-deprivation, revealing a nutrient-specific component acutely regulated by CB1 receptor blockade. Finally, peripheral blockade of sympathetic neurotransmission also blunted central effects of CB1 receptor blockade, such as fear responses and anxiety-like behaviors. These data demonstrate that, independently of their site of origin, important effects of CB1 receptor blockade are expressed via activation of peripheral sympathetic activity. Thus, CB1 receptors modulate bidirectional circuits between the periphery and the brain to regulate feeding and other behaviors. PMID:23487769

Modeling and control parameters for GMAW, short-circuiting transfer

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

Cook, G.E.; DeLapp, D.R.; Barnett, R.J.

1996-12-31

Digital signal processing was used to analyze the electrical arc signals of the gas metal arc welding process with short-circuiting transfer. Among the features extracted were arc voltage and current (both average and peak values), short-circuiting frequency, arc period, shorting period, and the ratio of the arcing to shorting period. Additionally , a Joule heating model was derived which accurately predicted the melt-back distance during each short. The short-circuiting frequency, the ratio of the arc period to short periods, and the melt-back distance were found to be good indicators for monitoring and control of stable arc conditions.

Synthetic gene circuits for metabolic control: design trade-offs and constraints

PubMed Central

Oyarzún, Diego A.; Stan, Guy-Bart V.

2013-01-01

A grand challenge in synthetic biology is to push the design of biomolecular circuits from purely genetic constructs towards systems that interface different levels of the cellular machinery, including signalling networks and metabolic pathways. In this paper, we focus on a genetic circuit for feedback regulation of unbranched metabolic pathways. The objective of this feedback system is to dampen the effect of flux perturbations caused by changes in cellular demands or by engineered pathways consuming metabolic intermediates. We consider a mathematical model for a control circuit with an operon architecture, whereby the expression of all pathway enzymes is transcriptionally repressed by the metabolic product. We address the existence and stability of the steady state, the dynamic response of the network under perturbations, and their dependence on common tuneable knobs such as the promoter characteristic and ribosome binding site (RBS) strengths. Our analysis reveals trade-offs between the steady state of the enzymes and the intermediates, together with a separation principle between promoter and RBS design. We show that enzymatic saturation imposes limits on the parameter design space, which must be satisfied to prevent metabolite accumulation and guarantee the stability of the network. The use of promoters with a broad dynamic range and a small leaky expression enlarges the design space. Simulation results with realistic parameter values also suggest that the control circuit can effectively upregulate enzyme production to compensate flux perturbations. PMID:23054953

Design of a signal conditioner for the Fermilab Magnet Test Facility

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

Giannelli, Pietro

2012-01-01

This thesis describes the design of a remotely-programmable signal conditioner for the harmonic measurement of accelerator magnets. A 10-channel signal conditioning circuit featuring bucking capabilities was designed from scratch and implemented to the level of the printed circuit board layout. Other system components were chosen from those available on the market. Software design was started with the definition of routine procedures. This thesis is part of an upgrade project for replacing obsolescent automated test equipment belonging to the Fermilab Magnet Test Facility. The design started with a given set of requirements. Using a top-down approach, all the circuits were designedmore » and their expected performances were theoretically predicted and simulated. A limited prototyping phase followed. The printed circuit boards were laid out and routed using a CAD software and focusing the design on maximum electromagnetic interference immunity. An embedded board was selected for controlling and interfacing the signal conditioning circuitry with the instrumentation network. Basic low level routines for hardware access were defined. This work covered the entire design process of the signal conditioner, resulting in a project ready for manufacturing. The expected performances are in line with the requirements and, in the cases where this was not possible, approval of trade-offs was sought and received from the end users. Part I deals with the global structure of the signal conditioner and the subdivision in functional macro-blocks. Part II treats the hardware design phase in detail, covering the analog and digital circuits, the printed circuit layouts, the embedded controller and the power supply selection. Part III deals with the basic hardware-related routines to be implemented in the final software.« less

Model-based evaluation of the short-circuited tripolar cuff configuration.

PubMed

Andreasen, Lotte N S; Struijk, Johannes J

2006-05-01

Recordings of neural information for use as feedback in functional electrical stimulation are often contaminated with interfering signals from muscles and from stimulus pulses. The cuff electrode used for the neural recording can be optimized to improve the S/I ratio. In this work, we evaluate a model of both the nerve signal and the interfering signals recorded by a cuff, and subsequently use this model to study the signal to interference ratio of different cuff designs and to evaluate a recently introduced short-circuited tripolar cuff configuration. The results of the model showed good agreement with results from measurements in rabbits and confirmed the superior performance of the short-circuited tripolar configuration as compared with the traditionally used tripolar configuration.

Energy storage cell impedance measuring apparatus, methods and related systems

DOEpatents

Morrison, John L.; Morrison, William H.; Christophersen, Jon P.

2017-12-26

Energy storage cell impedance testing devices, circuits, and related methods are disclosed. An energy storage cell impedance measuring device includes a sum of sinusoids (SOS) current excitation circuit including differential current sources configured to isolate a ground terminal of the differential current sources from a positive terminal and a negative terminal of an energy storage cell. A method includes applying an SOS signal comprising a sum of sinusoidal current signals to the energy storage cell with the SOS current excitation circuit, each of the sinusoidal current signals oscillating at a different one of a plurality of different frequencies. The method also includes measuring an electrical signal at a positive terminal and a negative terminal of the energy storage cell, and computing an impedance of the energy storage cell at each of the plurality of different frequencies using the measured electrical signal.

Coupling Spatial Segregation with Synthetic Circuits to Control Bacterial Survival (Open Access)

DTIC Science & Technology

2016-02-29

Subject Categories Synthetic Biology & Biotechnology; Quantitative Biology & Dynamical Systems DOI 10.15252/msb.20156567 | Received 9 September 2015...survival. Experimentally , we program collective survival using three different gene circuits, which allow us to evaluate the modularity of the...QS-CAT circuit depends on QS regulation. The QS-BlaM circuit depends on both QS regulation and enzyme release (by lysis and export). G–I Experimental

UHF FM receiver having improved frequency stability and low RFI emission

DOEpatents

Lupinetti, Francesco

1990-02-27

A UHF receiver which converts UHF modulated carrier signals to baseband video signals without any heterodyne or frequency conversion stages. A bandpass filter having a fixed frequency first filters the signals. A low noise amplifier amplifies the filtered signal and applies the signal through further amplification stages to a limited FM demodulator circuit. The UHF signal is directly converted to a baseband video signal. The baseband video signal is clamped by a clamping circuit before driving a monitor. Frequency stability for the receivers is at a theoretical maximum, and interference to adjacent receivers is eliminated due to the absence of a local oscillator.

Sensor readout detector circuit

DOEpatents

Chu, Dahlon D.; Thelen, Jr., Donald C.

1998-01-01

A sensor readout detector circuit is disclosed that is capable of detecting sensor signals down to a few nanoamperes or less in a high (microampere) background noise level. The circuit operates at a very low standby power level and is triggerable by a sensor event signal that is above a predetermined threshold level. A plurality of sensor readout detector circuits can be formed on a substrate as an integrated circuit (IC). These circuits can operate to process data from an array of sensors in parallel, with only data from active sensors being processed for digitization and analysis. This allows the IC to operate at a low power level with a high data throughput for the active sensors. The circuit may be used with many different types of sensors, including photodetectors, capacitance sensors, chemically-sensitive sensors or combinations thereof to provide a capability for recording transient events or for recording data for a predetermined period of time following an event trigger. The sensor readout detector circuit has applications for portable or satellite-based sensor systems.

Sensor readout detector circuit

DOEpatents

Chu, D.D.; Thelen, D.C. Jr.

1998-08-11

A sensor readout detector circuit is disclosed that is capable of detecting sensor signals down to a few nanoamperes or less in a high (microampere) background noise level. The circuit operates at a very low standby power level and is triggerable by a sensor event signal that is above a predetermined threshold level. A plurality of sensor readout detector circuits can be formed on a substrate as an integrated circuit (IC). These circuits can operate to process data from an array of sensors in parallel, with only data from active sensors being processed for digitization and analysis. This allows the IC to operate at a low power level with a high data throughput for the active sensors. The circuit may be used with many different types of sensors, including photodetectors, capacitance sensors, chemically-sensitive sensors or combinations thereof to provide a capability for recording transient events or for recording data for a predetermined period of time following an event trigger. The sensor readout detector circuit has applications for portable or satellite-based sensor systems. 6 figs.

Addressing On-Chip Power Converstion and Dissipation Issues in Many-Core System-on-a-Chip Based on Conventional Silicon and Emerging Nanotechnologies

NASA Astrophysics Data System (ADS)

Ashenafi, Emeshaw

Integrated circuits (ICs) are moving towards system-on-a-chip (SOC) designs. SOC allows various small and large electronic systems to be implemented in a single chip. This approach enables the miniaturization of design blocks that leads to high density transistor integration, faster response time, and lower fabrication costs. To reap the benefits of SOC and uphold the miniaturization of transistors, innovative power delivery and power dissipation management schemes are paramount. This dissertation focuses on on-chip integration of power delivery systems and managing power dissipation to increase the lifetime of energy storage elements. We explore this problem from two different angels: On-chip voltage regulators and power gating techniques. On-chip voltage regulators reduce parasitic effects, and allow faster and efficient power delivery for microprocessors. Power gating techniques, on the other hand, reduce the power loss incurred by circuit blocks during standby mode. Power dissipation (Ptotal = Pstatic and Pdynamic) in a complementary metal-oxide semiconductor (CMOS) circuit comes from two sources: static and dynamic. A quadratic dependency on the dynamic switching power and a more than linear dependency on static power as a form of gate leakage (subthreshold current) exist. To reduce dynamic power loss, the supply power should be reduced. A significant reduction in power dissipation occurs when portions of a microprocessor operate at a lower voltage level. This reduction in supply voltage is achieved via voltage regulators or converters. Voltage regulators are used to provide a stable power supply to the microprocessor. The conventional off-chip switching voltage regulator contains a passive floating inductor, which is difficult to be implemented inside the chip due to excessive power dissipation and parasitic effects. Additionally, the inductor takes a very large chip area while hampering the scaling process. These limitations make passive inductor based on-chip regulator design very unattractive for SOC integration and multi-/many-core environments. To circumvent the challenges, three alternative techniques based on active circuit elements to replace the passive LC filter of the buck convertor are developed. The first inductorless on-chip switching voltage regulator architecture is based on a cascaded 2nd order multiple feedback (MFB) low-pass filter (LPF). This design has the ability to modulate to multiple voltage settings via pulse-with modulation (PWM). The second approach is a supplementary design utilizing a hybrid low drop-out scheme to lower the output ripple of the switching regulator over a wider frequency range. The third design approach allows the integration of an entire power management system within a single chipset by combining a highly efficient switching regulator with an intermittently efficient linear regulator (area efficient), for robust and highly efficient on-chip regulation. The static power (Pstatic) or subthreshold leakage power (Pleak) increases with technology scaling. To mitigate static power dissipation, power gating techniques are implemented. Power gating is one of the popular methods to manage leakage power during standby periods in low-power high-speed IC design. It works by using transistor based switches to shut down part of the circuit block and put them in the idle mode. The efficiency of a power gating scheme involves minimum Ioff and high Ion for the sleep transistor. A conventional sleep transistor circuit design requires an additional header, footer, or both switches to turn off the logic block. This additional transistor causes signal delay and increases the chip area. We propose two innovative designs for next generation sleep transistor designs. For an above threshold operation, we present a sleep transistor design based on fully depleted silicon-on-insulator (FDSOI) device. For a subthreshold circuit operation, we implement a sleep transistor utilizing the newly developed silicon-on-ferroelectric-insulator field effect transistor (SOFFET). In both of the designs, the ability to control the threshold voltage via bias voltage at the back gate makes both devices more flexible for sleep transistors design than a bulk MOSFET. The proposed approaches simplify the design complexity, reduce the chip area, eliminate the voltage drop by sleep transistor, and improve power dissipation. In addition, the design provides a dynamically controlled Vt for times when the circuit needs to be in a sleep or switching mode.

Optically Isolated Control of the MOCHI LabJet High Power Pulsed Plasma Experiment

NASA Astrophysics Data System (ADS)

Carroll, Evan; Quinley, Morgan; von der Linden, Jens; You, Setthivoine

2014-10-01

The MOCHI LabJet experiment designed to investigate the dynamics of astrophysical jets at the University of Washington, requires high energy pulsed power supplies for plasma generation and sustainment. Two 600 μ F, 10 kV DC, pulse forming, power supplies have been specifically developed for this application. For safe and convenient user operation, the power supplies are controlled remotely with optical isolation. Three input voltage signals are required for relay actuation, adjusting bank charging voltage, and to fire the experiment: long duration DC signals, long duration user adjustable DC signals and fast trigger pulses with < μ s rise times. These voltage signals are generated from National Instruments timing cards via LabVIEW and are converted to optical signals by coupling photodiodes with custom electronic circuits. At the experiment, the optical signals are converted back to usable voltage signals using custom circuits. These custom circuits and experimental set-up are presented. This work is supported by US DOE Grant DE-SC0010340.

REGENERATIVE TRANSISTOR AMPLIFIER

DOEpatents

Kabell, L.J.

1958-11-25

Electrical circults for use in computers and the like are described. particularly a regenerative bistable transistor amplifler which is iurned on by a clock signal when an information signal permits and is turned off by the clock signal. The amplifier porforms the above function with reduced power requirements for the clock signal and circuit operation. The power requirements are reduced in one way by employing transformer coupling which increases the collector circuit efficiency by eliminating the loss of power in the collector load resistor.

Capacitive charge generation apparatus and method for testing circuits

DOEpatents

Cole, E.I. Jr.; Peterson, K.A.; Barton, D.L.

1998-07-14

An electron beam apparatus and method for testing a circuit are disclosed. The electron beam apparatus comprises an electron beam incident on an outer surface of an insulating layer overlying one or more electrical conductors of the circuit for generating a time varying or alternating current electrical potential on the surface; and a measurement unit connected to the circuit for measuring an electrical signal capacitively coupled to the electrical conductors to identify and map a conduction state of each of the electrical conductors, with or without an electrical bias signal being applied to the circuit. The electron beam apparatus can further include a secondary electron detector for forming a secondary electron image for registration with a map of the conduction state of the electrical conductors. The apparatus and method are useful for failure analysis or qualification testing to determine the presence of any open-circuits or short-circuits, and to verify the continuity or integrity of electrical conductors buried below an insulating layer thickness of 1-100 {micro}m or more without damaging or breaking down the insulating layer. The types of electrical circuits that can be tested include integrated circuits, multi-chip modules, printed circuit boards and flexible printed circuits. 7 figs.

Capacitive charge generation apparatus and method for testing circuits

DOEpatents

Cole, Jr., Edward I.; Peterson, Kenneth A.; Barton, Daniel L.

1998-01-01

An electron beam apparatus and method for testing a circuit. The electron beam apparatus comprises an electron beam incident on an outer surface of an insulating layer overlying one or more electrical conductors of the circuit for generating a time varying or alternating current electrical potential on the surface; and a measurement unit connected to the circuit for measuring an electrical signal capacitively coupled to the electrical conductors to identify and map a conduction state of each of the electrical conductors, with or without an electrical bias signal being applied to the circuit. The electron beam apparatus can further include a secondary electron detector for forming a secondary electron image for registration with a map of the conduction state of the electrical conductors. The apparatus and method are useful for failure analysis or qualification testing to determine the presence of any open-circuits or short-circuits, and to verify the continuity or integrity of electrical conductors buried below an insulating layer thickness of 1-100 .mu.m or more without damaging or breaking down the insulating layer. The types of electrical circuits that can be tested include integrated circuits, multi-chip modules, printed circuit boards and flexible printed circuits.

A programmable CCD driver circuit for multiphase CCD operation

NASA Technical Reports Server (NTRS)

Ewin, Audrey J.; Reed, Kenneth V.

1989-01-01

A programmable CCD (charge-coupled device) driver circuit was designed to drive CCDs in multiphased modes. The purpose of the drive electronics is to operate developmental CCD imaging arrays for NASA's tiltable moderate resolution imaging spectrometer (MODIS-T). Five objectives for the driver were considered during its design: (1) the circuit drives CCD electrode voltages between 0 V and +30 V to produce reasonable potential wells, (2) the driving sequence is started with one input signal, (3) the driving sequence is started with one input signal, (4) the circuit allows programming of frame sequences required by arrays of any size, (5) it produces interfacing signals for the CCD and the DTF (detector test facility). Simulation of the driver verified its function with the master clock running up to 10 MHz. This suggests a maximum rate of 400,000 pixels/s. Timing and packaging parameters were verified. The design uses 54 TTL (transistor-transistor logic) chips. Two versions of hardware were fabricated: wirewrap and printed circuit board. Both were verified functionally with a logic analyzer.

Accurate reliability analysis method for quantum-dot cellular automata circuits

NASA Astrophysics Data System (ADS)

Cui, Huanqing; Cai, Li; Wang, Sen; Liu, Xiaoqiang; Yang, Xiaokuo

2015-10-01

Probabilistic transfer matrix (PTM) is a widely used model in the reliability research of circuits. However, PTM model cannot reflect the impact of input signals on reliability, so it does not completely conform to the mechanism of the novel field-coupled nanoelectronic device which is called quantum-dot cellular automata (QCA). It is difficult to get accurate results when PTM model is used to analyze the reliability of QCA circuits. To solve this problem, we present the fault tree models of QCA fundamental devices according to different input signals. After that, the binary decision diagram (BDD) is used to quantitatively investigate the reliability of two QCA XOR gates depending on the presented models. By employing the fault tree models, the impact of input signals on reliability can be identified clearly and the crucial components of a circuit can be found out precisely based on the importance values (IVs) of components. So this method is contributive to the construction of reliable QCA circuits.

Regulatory states in the developmental control of gene expression.

PubMed

Peter, Isabelle S

2017-09-01

A growing body of evidence shows that gene expression in multicellular organisms is controlled by the combinatorial function of multiple transcription factors. This indicates that not the individual transcription factors or signaling molecules, but the combination of expressed regulatory molecules, the regulatory state, should be viewed as the functional unit in gene regulation. Here, I discuss the concept of the regulatory state and its proposed role in the genome-wide control of gene expression. Recent analyses of regulatory gene expression in sea urchin embryos have been instrumental for solving the genomic control of cell fate specification in this system. Some of the approaches that were used to determine the expression of regulatory states during sea urchin embryogenesis are reviewed. Significant developmental changes in regulatory state expression leading to the distinct specification of cell fates are regulated by gene regulatory network circuits. How these regulatory state transitions are encoded in the genome is illuminated using the sea urchin endoderm-mesoderms cell fate decision circuit as an example. These observations highlight the importance of considering developmental gene regulation, and the function of individual transcription factors, in the context of regulatory states. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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

Wong, Melissa; Bolovan-Fritts, Cynthia; Dar, Roy D.

Signal transduction circuits have long been known to differentiate between signals by amplifying inputs to different levels. Here, we describe a novel transcriptional circuitry that dynamically converts greater input levels into faster rates, without increasing the final equilibrium level (i.e. a rate amplifier). We utilize time-lapse microscopy to study human herpesvirus (cytomegalovirus) infection of live cells in real time. Strikingly, our results show that transcriptional activators accelerate viral gene expression in single cells without amplifying the steady-state levels of gene products in these cells. Experiment and modeling show that rate amplification operates by dynamically manipulating the traditional gain-bandwidth feedback relationshipmore » from electrical circuit theory to convert greater input levels into faster rates, and is driven by highly self-cooperative transcriptional feedback encoded by the virus s essential transactivator, IE2. This transcriptional rate-amplifier provides a significant fitness advantage for the virus and for minimal synthetic circuits. In general, rate-amplifiers may provide a mechanism for signal-transduction circuits to respond quickly to external signals without increasing steady-state levels of potentially cytotoxic molecules.« less

OCD-like behavior is caused by dysfunction of thalamo-amygdala circuits and upregulated TrkB/ERK-MAPK signaling as a result of SPRED2 deficiency

PubMed Central

Ullrich, M; Weber, M; Post, A M; Popp, S; Grein, J; Zechner, M; Guerrero González, H; Kreis, A; Schmitt, A G; Üçeyler, N; Lesch, K-P; Schuh, K

2018-01-01

Obsessive-compulsive disorder (OCD) is a common neuropsychiatric disease affecting about 2% of the general population. It is characterized by persistent intrusive thoughts and repetitive ritualized behaviors. While gene variations, malfunction of cortico-striato-thalamo-cortical (CSTC) circuits, and dysregulated synaptic transmission have been implicated in the pathogenesis of OCD, the underlying mechanisms remain largely unknown. Here we show that OCD-like behavior in mice is caused by deficiency of SPRED2, a protein expressed in various brain regions and a potent inhibitor of Ras/ERK-MAPK signaling. Excessive self-grooming, reflecting OCD-like behavior in rodents, resulted in facial skin lesions in SPRED2 knockout (KO) mice. This was alleviated by treatment with the selective serotonin reuptake inhibitor fluoxetine. In addition to the previously suggested involvement of cortico-striatal circuits, electrophysiological measurements revealed altered transmission at thalamo-amygdala synapses and morphological differences in lateral amygdala neurons of SPRED2 KO mice. Changes in synaptic function were accompanied by dysregulated expression of various pre- and postsynaptic proteins in the amygdala. This was a result of altered gene transcription and triggered upstream by upregulated tropomyosin receptor kinase B (TrkB)/ERK-MAPK signaling in the amygdala of SPRED2 KO mice. Pathway overactivation was mediated by increased activity of TrkB, Ras, and ERK as a specific result of SPRED2 deficiency and not elicited by elevated brain-derived neurotrophic factor levels. Using the MEK inhibitor selumetinib, we suppressed TrkB/ERK-MAPK pathway activity in vivo and reduced OCD-like grooming in SPRED2 KO mice. Altogether, this study identifies SPRED2 as a promising new regulator, TrkB/ERK-MAPK signaling as a novel mediating mechanism, and thalamo-amygdala synapses as critical circuitry involved in the pathogenesis of OCD. PMID:28070119

Central Control of Brown Adipose Tissue Thermogenesis

PubMed Central

Morrison, Shaun F.; Madden, Christopher J.; Tupone, Domenico

2011-01-01

Thermogenesis, the production of heat energy, is an essential component of the homeostatic repertoire to maintain body temperature during the challenge of low environmental temperature and plays a key role in elevating body temperature during the febrile response to infection. Mitochondrial oxidation in brown adipose tissue (BAT) is a significant source of neurally regulated metabolic heat production in many species from mouse to man. BAT thermogenesis is regulated by neural networks in the central nervous system which responds to feedforward afferent signals from cutaneous and core body thermoreceptors and to feedback signals from brain thermosensitive neurons to activate BAT sympathetic nerve activity. This review summarizes the research leading to a model of the feedforward reflex pathway through which environmental cold stimulates BAT thermogenesis and includes the influence on this thermoregulatory network of the pyrogenic mediator, prostaglandin E2, to increase body temperature during fever. The cold thermal afferent circuit from cutaneous thermal receptors, through second-order thermosensory neurons in the dorsal horn of the spinal cord ascends to activate neurons in the lateral parabrachial nucleus which drive GABAergic interneurons in the preoptic area (POA) to inhibit warm-sensitive, inhibitory output neurons of the POA. The resulting disinhibition of BAT thermogenesis-promoting neurons in the dorsomedial hypothalamus activates BAT sympathetic premotor neurons in the rostral ventromedial medulla, including the rostral raphe pallidus, which provide excitatory, and possibly disinhibitory, inputs to spinal sympathetic circuits to drive BAT thermogenesis. Other recently recognized central sites influencing BAT thermogenesis and energy expenditure are also described. PMID:22389645

Central control of thermogenesis in mammals

PubMed Central

Morrison, Shaun F.; Nakamura, Kazuhiro; Madden, Christopher J.

2008-01-01

Thermogenesis, the production of heat energy, is an essential component of the homeostatic repertoire to maintain body temperature in mammals and birds during the challenge of low environmental temperature and plays a key role in elevating body temperature during the febrile response to infection. The primary sources of neurally regulated metabolic heat production are mitochondrial oxidation in brown adipose tissue, increases in heart rate and shivering in skeletal muscle. Thermogenesis is regulated in each of these tissues by parallel networks in the central nervous system, which respond to feedforward afferent signals from cutaneous and core body thermoreceptors and to feedback signals from brain thermosensitive neurons to activate the appropriate sympathetic and somatic efferents. This review summarizes the research leading to a model of the feedforward reflex pathway through which environmental cold stimulates thermogenesis and discusses the influence on this thermoregulatory network of the pyrogenic mediator, prostaglandin E2, to increase body temperature. The cold thermal afferent circuit from cutaneous thermal receptors ascends via second-order thermosensory neurons in the dorsal horn of the spinal cord to activate neurons in the lateral parabrachial nucleus, which drive GABAergic interneurons in the preoptic area to inhibit warm-sensitive, inhibitory output neurons of the preoptic area. The resulting disinhibition of thermogenesis-promoting neurons in the dorsomedial hypothalamus and possibly of sympathetic and somatic premotor neurons in the rostral ventromedial medulla, including the raphe pallidus, activates excitatory inputs to spinal sympathetic and somatic motor circuits to drive thermogenesis. PMID:18469069

The research of digital circuit system for high accuracy CCD of portable Raman spectrometer

NASA Astrophysics Data System (ADS)

Yin, Yu; Cui, Yongsheng; Zhang, Xiuda; Yan, Huimin

2013-08-01

The Raman spectrum technology is widely used for it can identify various types of molecular structure and material. The portable Raman spectrometer has become a hot direction of the spectrometer development nowadays for its convenience in handheld operation and real-time detection which is superior to traditional Raman spectrometer with heavy weight and bulky size. But there is still a gap for its measurement sensitivity between portable and traditional devices. However, portable Raman Spectrometer with Shell-Isolated Nanoparticle-Enhanced Raman Spectroscopy (SHINERS) technology can enhance the Raman signal significantly by several orders of magnitude, giving consideration in both measurement sensitivity and mobility. This paper proposed a design and implementation of driver and digital circuit for high accuracy CCD sensor, which is core part of portable spectrometer. The main target of the whole design is to reduce the dark current generation rate and increase signal sensitivity during the long integration time, and in the weak signal environment. In this case, we use back-thinned CCD image sensor from Hamamatsu Corporation with high sensitivity, low noise and large dynamic range. In order to maximize this CCD sensor's performance and minimize the whole size of the device simultaneously to achieve the project indicators, we delicately designed a peripheral circuit for the CCD sensor. The design is mainly composed with multi-voltage circuit, sequential generation circuit, driving circuit and A/D transition parts. As the most important power supply circuit, the multi-voltage circuits with 12 independent voltages are designed with reference power supply IC and set to specified voltage value by the amplifier making up the low-pass filter, which allows the user to obtain a highly stable and accurate voltage with low noise. What's more, to make our design easy to debug, CPLD is selected to generate sequential signal. The A/D converter chip consists of a correlated double sampler; a digitally controlled variable gain amplifier and a 16-bit A/D converter which can help improve the data quality. And the acquired digital signals are transmitted into the computer via USB 2.0 data port. Our spectrometer with SHINERS technology can acquire the Raman spectrum signals efficiently in long time integration and weak signal environment, and the size of our system is well controlled for portable application.

Differential transimpedance amplifier circuit for correlated differential amplification

DOEpatents

Gresham, Christopher A [Albuquerque, NM; Denton, M Bonner [Tucson, AZ; Sperline, Roger P [Tucson, AZ

2008-07-22

A differential transimpedance amplifier circuit for correlated differential amplification. The amplifier circuit increase electronic signal-to-noise ratios in charge detection circuits designed for the detection of very small quantities of electrical charge and/or very weak electromagnetic waves. A differential, integrating capacitive transimpedance amplifier integrated circuit comprising capacitor feedback loops performs time-correlated subtraction of noise.

PULSE AMPLIFIER

DOEpatents

Johnstone, C.W.

1958-06-17

The improvement of pulse amplifiers used with scintillation detectors is described. The pulse amplifier circuit has the advantage of reducing the harmful effects of overloading cause by large signal inputs. In general the pulse amplifier circuit comprises two amplifier tubes with the input pulses applied to one amplifier grid and coupled to the second amplifier tube through a common cathode load. The output of the second amplifier is coupled from the plate circuit to a cathode follower tube grid and a diode tube in connected from grid to cathode of the cathode follower tube. Degenerative feedback is provided in the second amplifier by coupling a signal from the cathode follower cathode to the second amplifier grid. The circuit proqides moderate gain stability, and overload protection for subsequent pulse circuits.

Induction voidmeter

DOEpatents

Anderson, T.T.; Roop, C.J.; Schmidt, K.J.; Brewer, J.

1983-12-21

An induction voidmeter for detecting voids in a conductive fluid may comprise: a four arm bridge circuit having two adjustable circuit elements connected as opposite arms of said bridge, an input branch, and an output branch; two induction coils, bifilarly wound together, connected as the remaining two opposing arms of said bridge circuit and positioned such that the conductive fluid passes through said coils; means for applying an AC excitation signal to said input branch; and means for detecting the output signal generated in response to said excitation signal across said output branch. The induction coils may be located outside or inside a non-magnetic pipe containing the conductive fluid.

Nuclear sensor signal processing circuit

DOEpatents

Kallenbach, Gene A [Bosque Farms, NM; Noda, Frank T [Albuquerque, NM; Mitchell, Dean J [Tijeras, NM; Etzkin, Joshua L [Albuquerque, NM

2007-02-20

An apparatus and method are disclosed for a compact and temperature-insensitive nuclear sensor that can be calibrated with a non-hazardous radioactive sample. The nuclear sensor includes a gamma ray sensor that generates tail pulses from radioactive samples. An analog conditioning circuit conditions the tail-pulse signals from the gamma ray sensor, and a tail-pulse simulator circuit generates a plurality of simulated tail-pulse signals. A computer system processes the tail pulses from the gamma ray sensor and the simulated tail pulses from the tail-pulse simulator circuit. The nuclear sensor is calibrated under the control of the computer. The offset is adjusted using the simulated tail pulses. Since the offset is set to zero or near zero, the sensor gain can be adjusted with a non-hazardous radioactive source such as, for example, naturally occurring radiation and potassium chloride.

Long-Term Plasticity of Neurotransmitter Release: Emerging Mechanisms and Contributions to Brain Function and Disease.

PubMed

Monday, Hannah R; Younts, Thomas J; Castillo, Pablo E

2018-04-25

Long-lasting changes of brain function in response to experience rely on diverse forms of activity-dependent synaptic plasticity. Chief among them are long-term potentiation and long-term depression of neurotransmitter release, which are widely expressed by excitatory and inhibitory synapses throughout the central nervous system and can dynamically regulate information flow in neural circuits. This review article explores recent advances in presynaptic long-term plasticity mechanisms and contributions to circuit function. Growing evidence indicates that presynaptic plasticity may involve structural changes, presynaptic protein synthesis, and transsynaptic signaling. Presynaptic long-term plasticity can alter the short-term dynamics of neurotransmitter release, thereby contributing to circuit computations such as novelty detection, modifications of the excitatory/inhibitory balance, and sensory adaptation. In addition, presynaptic long-term plasticity underlies forms of learning and its dysregulation participates in several neuropsychiatric conditions, including schizophrenia, autism, intellectual disabilities, neurodegenerative diseases, and drug abuse. Expected final online publication date for the Annual Review of Neuroscience Volume 41 is July 8, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Global synchronization of parallel processors using clock pulse width modulation

DOEpatents

Chen, Dong; Ellavsky, Matthew R.; Franke, Ross L.; Gara, Alan; Gooding, Thomas M.; Haring, Rudolf A.; Jeanson, Mark J.; Kopcsay, Gerard V.; Liebsch, Thomas A.; Littrell, Daniel; Ohmacht, Martin; Reed, Don D.; Schenck, Brandon E.; Swetz, Richard A.

2013-04-02

A circuit generates a global clock signal with a pulse width modification to synchronize processors in a parallel computing system. The circuit may include a hardware module and a clock splitter. The hardware module may generate a clock signal and performs a pulse width modification on the clock signal. The pulse width modification changes a pulse width within a clock period in the clock signal. The clock splitter may distribute the pulse width modified clock signal to a plurality of processors in the parallel computing system.

Design issues of a low cost lock-in amplifier readout circuit for an infrared detector

NASA Astrophysics Data System (ADS)

Scheepers, L.; Schoeman, J.

2014-06-01

In the past, high resolution thermal sensors required expensive cooling techniques making the early thermal imagers expensive to operate and cumbersome to transport, limiting them mainly to military applications. However, the introduction of uncooled microbolometers has overcome many of earlier problems and now shows great potential for commercial optoelectric applications. The structure of uncooled microbolometer sensors, especially their smaller size, makes them attractive in low cost commercial applications requiring high production numbers with relatively low performance requirements. However, the biasing requirements of these microbolometers cause these sensors to generate a substantial amount of noise on the output measurements due to self-heating. Different techniques to reduce this noise component have been attempted, such as pulsed biasing currents and the use of blind bolometers as common mode reference. These techniques proved to either limit the performance of the microbolometer or increase the cost of their implementation. The development of a low cost lock-in amplifier provides a readout technique to potentially overcome these challenges. High performance commercial lock-in amplifiers are very expensive. Using this as a readout circuit for a microbolometer will take away from the low manufacturing cost of the detector array. Thus, the purpose of this work was to develop a low cost readout circuit using the technique of phase sensitive detection and customizing this as a readout circuit for microbolometers. The hardware and software of the readout circuit was designed and tested for improvement of the signal-to-noise ratio (SNR) of the microbolometer signal. An optical modulation system was also developed in order to effectively identify the desired signal from the noise with the use of the readout circuit. A data acquisition and graphical user interface sub system was added in order to display the signal recovered by the readout circuit. The readout circuit was able to enhance the SNR of the microbolometer signal significantly. It was shown that the quality of the phase sensitive detector plays a significant role in the effectiveness of the readout circuit to improve the SNR.

Short-Circuit Fault Detection and Classification Using Empirical Wavelet Transform and Local Energy for Electric Transmission Line.

PubMed

Huang, Nantian; Qi, Jiajin; Li, Fuqing; Yang, Dongfeng; Cai, Guowei; Huang, Guilin; Zheng, Jian; Li, Zhenxin

2017-09-16

In order to improve the classification accuracy of recognizing short-circuit faults in electric transmission lines, a novel detection and diagnosis method based on empirical wavelet transform (EWT) and local energy (LE) is proposed. First, EWT is used to deal with the original short-circuit fault signals from photoelectric voltage transformers, before the amplitude modulated-frequency modulated (AM-FM) mode with a compactly supported Fourier spectrum is extracted. Subsequently, the fault occurrence time is detected according to the modulus maxima of intrinsic mode function (IMF₂) from three-phase voltage signals processed by EWT. After this process, the feature vectors are constructed by calculating the LE of the fundamental frequency based on the three-phase voltage signals of one period after the fault occurred. Finally, the classifier based on support vector machine (SVM) which was constructed with the LE feature vectors is used to classify 10 types of short-circuit fault signals. Compared with complementary ensemble empirical mode decomposition with adaptive noise (CEEMDAN) and improved CEEMDAN methods, the new method using EWT has a better ability to present the frequency in time. The difference in the characteristics of the energy distribution in the time domain between different types of short-circuit faults can be presented by the feature vectors of LE. Together, simulation and real signals experiment demonstrate the validity and effectiveness of the new approach.

Short-Circuit Fault Detection and Classification Using Empirical Wavelet Transform and Local Energy for Electric Transmission Line

PubMed Central

Huang, Nantian; Qi, Jiajin; Li, Fuqing; Yang, Dongfeng; Cai, Guowei; Huang, Guilin; Zheng, Jian; Li, Zhenxin

2017-01-01

In order to improve the classification accuracy of recognizing short-circuit faults in electric transmission lines, a novel detection and diagnosis method based on empirical wavelet transform (EWT) and local energy (LE) is proposed. First, EWT is used to deal with the original short-circuit fault signals from photoelectric voltage transformers, before the amplitude modulated-frequency modulated (AM-FM) mode with a compactly supported Fourier spectrum is extracted. Subsequently, the fault occurrence time is detected according to the modulus maxima of intrinsic mode function (IMF2) from three-phase voltage signals processed by EWT. After this process, the feature vectors are constructed by calculating the LE of the fundamental frequency based on the three-phase voltage signals of one period after the fault occurred. Finally, the classifier based on support vector machine (SVM) which was constructed with the LE feature vectors is used to classify 10 types of short-circuit fault signals. Compared with complementary ensemble empirical mode decomposition with adaptive noise (CEEMDAN) and improved CEEMDAN methods, the new method using EWT has a better ability to present the frequency in time. The difference in the characteristics of the energy distribution in the time domain between different types of short-circuit faults can be presented by the feature vectors of LE. Together, simulation and real signals experiment demonstrate the validity and effectiveness of the new approach. PMID:28926953

Biophysical Network Modelling of the dLGN Circuit: Different Effects of Triadic and Axonal Inhibition on Visual Responses of Relay Cells.

PubMed

Heiberg, Thomas; Hagen, Espen; Halnes, Geir; Einevoll, Gaute T

2016-05-01

Despite its prominent placement between the retina and primary visual cortex in the early visual pathway, the role of the dorsal lateral geniculate nucleus (dLGN) in molding and regulating the visual signals entering the brain is still poorly understood. A striking feature of the dLGN circuit is that relay cells (RCs) and interneurons (INs) form so-called triadic synapses, where an IN dendritic terminal can be simultaneously postsynaptic to a retinal ganglion cell (GC) input and presynaptic to an RC dendrite, allowing for so-called triadic inhibition. Taking advantage of a recently developed biophysically detailed multicompartmental model for an IN, we here investigate putative effects of these different inhibitory actions of INs, i.e., triadic inhibition and standard axonal inhibition, on the response properties of RCs. We compute and investigate so-called area-response curves, that is, trial-averaged visual spike responses vs. spot size, for circular flashing spots in a network of RCs and INs. The model parameters are grossly tuned to give results in qualitative accordance with previous in vivo data of responses to such stimuli for cat GCs and RCs. We particularly investigate how the model ingredients affect salient response properties such as the receptive-field center size of RCs and INs, maximal responses and center-surround antagonisms. For example, while triadic inhibition not involving firing of IN action potentials was found to provide only a non-linear gain control of the conversion of input spikes to output spikes by RCs, axonal inhibition was in contrast found to substantially affect the receptive-field center size: the larger the inhibition, the more the RC center size shrinks compared to the GC providing the feedforward excitation. Thus, a possible role of the different inhibitory actions from INs to RCs in the dLGN circuit is to provide separate mechanisms for overall gain control (direct triadic inhibition) and regulation of spatial resolution (axonal inhibition) of visual signals sent to cortex.

Frequency control circuit for all-digital phase-lock loops

NASA Technical Reports Server (NTRS)

Anderson, T. O.

1973-01-01

Phase-lock loop references all its operations to fixed high-frequency service clock operating at highest speed which digital circuits permit. Wide-range control circuit provides linear control of frequency of reference signal. It requires only two counters in combination with control circuit consisting only of flip-flop and gate.

49 CFR 236.721 - Circuit, control.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Circuit, control. 236.721 Section 236.721..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.721 Circuit, control. An electrical circuit between a source of electric energy and a device which it operates. ...

49 CFR 236.721 - Circuit, control.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Circuit, control. 236.721 Section 236.721..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.721 Circuit, control. An electrical circuit between a source of electric energy and a device which it operates. ...

49 CFR 236.721 - Circuit, control.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Circuit, control. 236.721 Section 236.721..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.721 Circuit, control. An electrical circuit between a source of electric energy and a device which it operates. ...

49 CFR 236.721 - Circuit, control.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Circuit, control. 236.721 Section 236.721..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.721 Circuit, control. An electrical circuit between a source of electric energy and a device which it operates. ...