Cooperative Amplification Research Articles

Cooperative amplification of Prussian blue as a signal indicator and functionalized metal-organic framework-based electrochemical biosensor for an ultrasensitive HE4 assay

Human epididymis protein 4 (HE4), a diagnostic biomarker of ovarian cancer, is crucial for monitoring the early stage of the disease. Hence, it is highly important to develop simple, inexpensive, and user-friendly biosensors for sensitive and quantitative HE4 assays. Herein, a new sandwich-type electrochemical immunosensor based on Prussian blue (PB) as a signal indicator and functionalized metal-organic framework nanocompositesas efficient signal amplifiers was fabricated for quantitative analysis of HE4. In principle, ketjen black (KB) and AuNPs modified on TiMOF (TiMOF-KB@AuNPs) could accelerate electron transfer on the electrode surface and act as a matrix for the immobilization of antibodies via cross-linking to improve the determination sensitivity. The PB that covalently binds to labeled antibodies endows the biosensors with intense electrochemical signals. Furthermore, the concentration of HE4 could be indirectly detected by monitoring the electroactivity of PB. Benefiting from the high signal amplification ability of the PB and MOF nanocomposites, this strategy displayed a wide linear range (0.1–80 ng mL−1) and a lower detection limit (0.02 ng mL−1). Hence, this study demonstrated great promise for application in clinical ovarian cancer diagnosis and treatment, and provided a new platform for detecting other cancer biomarkers.

Cooperative Amplification of Au@FeCo as Mimetic Catalytic Nanozymes and Bicycled Hairpin Assembly for Ultrasensitive Electrochemical Biosensing.

Exploring the cooperative amplification of peroxidase-like metal nanocomposites and cycled hairpin assembly is intriguing for sensitive bioanalysis. Herein, we report the first design of a unique electrochemical biosensor based on mimicking Au@FeCo nanozymes and bicycled hairpin assembly (BHA) for synergistic signal amplification. By loading the enzyme-like FeCo alloy in Au nanoparticles (AuNPs), the as-synthesized Au@FeCo hybrids display great improvement of electronic conductivity and active surface area and excellent mimic catalase activity to H2O2 decomposition into •OH radicals. The immobilization of Au@FeCo in an electrode sensing interface is stabilized via the resulting electrodeposition in HAuCl4 while efficiently accelerating the electron transfer of electroactive ferrocene (Fc). Upon the immobilization of a helping hairpin (HH) via Au-S bonds, a specific DNA trigger (T*) is introduced to activate BHA operation through competitive strand displacement reactions among recognizing hairpin (RH), signaling hairpin (SH), and HH. T* and RH are rationally released to catalyze two cycles, in which the transient depletion of dsDNA intermediates rapidly drives the progressive hairpin assemblies to output more products SH·HH. Thus, the efficient amplification of Au@FeCo mimic catalase activity combined with BHA leads to a significantly increased current signal of Fc dependent on miRNA-21 analogous to T*, thereby directing the creation of a highly sensitive electrochemical biosensor having applicable potential in actual samples.

Self-amplified chain-shattering cinnamaldehyde-based poly(thioacetal) boosts cancer chemo-immunotherapy

The selective activation of stimuli-responsive polymers in the tumor microenvironment is a great concern to achieve intelligent cancer therapy, but most of them show inadequate response due to insufficient endogenous triggering agents. Herein, we rationally designed a reactive oxygen species (ROS)-responsive cinnamaldehyde (CA)-based poly(thioacetal), consisting of ROS-responsive thioacetal (TA) and ROS-generating agent CA, with self-amplified chain-shattering polymer degradation. The mechanism of self-amplified chain-shattering is that endogenous ROS as a triggering agent facilitates chain cleavage of TA with the release of CA, which in turn produces more ROS through mitochondrial dysfunction, resulting in an exponential polymer degradation cascade. The polymer can be further modified with anticancer drug doxorubicin (DOX) for cooperative amplification of oxidative stress and immunogenic cell death (ICD) of tumor cells, thereby boosting the effect of chemo-immunotherapy. The self-amplified chain-shattering polymer designed in this work holds great promise in developing stimuli-responsive polymers for efficient drug delivery. Statement of significanceThis study presented an approach to utilize self-amplified chain-shattering cinnamaldehyde-based poly (thioacetal) as a drug delivery system to restrain tumor growth and boost chemo-immunotherapy. The endogenous ROS as a triggering agent initiates the chain cleavage with the release of CA, which in turn produces ROS through mitochondria dysfunction, resulting in an exponential polymer degradation cascade and rapid drug release.

Dual-Engine Powered Paper Photoelectrochemical Platform Based on 3D DNA Nanomachine-Mediated CRISPR/Cas12a for Detection of Multiple miRNAs.

This work proposed a novel double-engine powered paper photoelectrochemical (PEC) biosensor based on an anode-cathode cooperative amplification strategy and various signal enhancement mechanisms, which realized the monitoring of multiple miRNAs (such as miRNA-141 and miRNA-21). Specifically, C3N4 quantum dots (QDs) sensitized ZnO nanostars and BiOI nanospheres simultaneously to construct a composite photoelectric layer that amplified the original photocurrent of the photoanode and photocathode, respectively. Through the independent design and partition of a flexible paper chip to functionalize injection holes and electrode areas, the bipolar combination completed the secondary upgrade of signals, which also provided biological reaction sites for multitarget detection. With the synergistic participation of a three-dimensional (3D) DNA nanomachine and programmable CRISPR/Cas12a shearing tool, C3N4 QDs lost their attachment away from the electrode surface to quench the signal. Moreover, electrode zoning significantly reduced the spatial cross talk of related substances for multitarget detection, while the universal trans-cleavage capability of CRISPR/Cas12a simplified the operation. The designed PEC biosensor revealed excellent linear ranges for detection of miRNA-141 and miRNA-21, for which the detection limits were 5.5 and 3.4 fM, respectively. With prominent selectivity and sensitivity, the platform established an effective approach for trace multitarget monitoring in clinical applications, and its numerous pioneering attempts owned favorable reference values.

Engineering an endonuclease-assisted rolling circle amplification synergistically catalyzing hairpin assembly mediated fluorescence platform for miR-21 detection

As one of the earliest miRNAs discovered in the human genome, miRNA-21 can provide vital information for the early diagnosis, drug treatment, and prognosis of cancers. Herein, we construct a fast, time-saving fluorescence detection system for miRNA-21 detection by coalescing the improved endonuclease-mediated rolling circle amplification with catalytic hairpin assembly (RCA-NESA-CHA). Firstly, the target miRNA cyclized the padlock, initiating rolling circle amplification (RCA) and extending a long-concatenated DNA. The modified Protector bonded with the long-strand DNA to generate an endonuclease-specific site and trigger the nicking process. Finally, DNA products with repetitive sequences not only recombined with the padlock to reactivate a new recycle of RCA but also triggered the catalytic hairpin assembly to form the H1–H2 complex, realizing the cooperative amplification of the signal. In this system, RCA-NESA and CHA were integrated into one step, which essentially simplifies the sensing process. Moreover, the introduction of the Protector would inhibit the extension reaction caused by the combination of the padlock and the RCA products, slowing down the non-specific reaction time and improving the sensitivity of the fluorescence detection system. Under the optimal experimental conditions, the fluorescence system achieved a limit-of-detection of 0.025 amol miR-21 in a 40 μL sample and successfully applied to miR-21 detection in serum samples from breast cancer patients, showing good agreement with the results of RT-PCR, which exhibited great potential in biomedical research and clinical diagnosis.

A direct, sensitive and high-throughput genus and species-specific molecular assay for large-scale malaria screening

BackgroundInfectious disease diagnostics often requires sensitive molecular assays that identify at both genus and species levels. For large scale screening, such as malaria screening for elimination, diagnostic assay can be a challenge, as both the throughput and cost of the assay must be considered. The requirement of nucleic acid extraction hampers the throughput of most molecular assays. Co-amplification of multiple species or multiplex identification either can result in missed diagnosis or are too costly for large-scale screening. A genus- and species-specific diagnostic assay with simplified procedure, high sensitivity and throughput is still needed. This study aimed to develop a sensitive and high-throughput approach for large-scale infectious disease screening.MethodsWe developed multi-section Capture and Ligation Probe PCR (mCLIP-PCR) for the direct detection of RNA without extraction and reverse transcription. Multiple tailed sandwich hybridization probes were used to bind at genus- and species-specific sections of the target RNA to cooperatively capture the target onto a 96-well plate. After enzymatic ligation of the bound probes, a single-stranded DNA formed at each section with distinct tail sequence at the ends. They were separately PCR-amplified with primers corresponding to tail sequences for genus or species identification. We applied the method to the active screening of Plasmodium infections of 4,580 asymptomatic dried blood spot samples collected in malaria endemic areas and compared the results with standard qPCR using linear regression.ResultsWith multi-section cooperative capture but separate amplification strategy, we accurately identified genus Plasmodium and species P. falciparum and P. vivax without RNA extraction, with favorable sensitivities among the published reports. In the active screening, our method identified all 53 positive infections including two mixed infections, and two P. vivax infections that were missed by standard qPCR.ConclusionsmCLIP-PCR provides a sensitive and high-throughput approach to large-scale infectious disease screening with low cost and labor, making it a valuable tool for malaria elimination in endemic region.Graphical

NIR-II-driven and glutathione depletion-enhanced hypoxia-irrelevant free radical nanogenerator for combined cancer therapy

BackgroundThough the combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT) appears to be very attractive in cancer treatment, hypoxia and overproduced glutathione (GSH) in the tumor microenvironment (TME) limit their efficacy for further application.ResultsIn this work, a smart hypoxia-irrelevant free radical nanogenerator (AIPH/PDA@CuS/ZIF-8, denoted as APCZ) was synthesized in situ via coating copper sulphide (CuS)-embedded zeolitic imidazolate framework-8 (ZIF-8) on the free radical initiator 2,2′-azobis[2-(2-imidazolin-2-yl)propane]-dihydrochloride (AIPH)-loaded polydopamine (PDA). APCZ showed promising GSH-depleting ability and near-infrared (NIR)-II photothermal performance for combined cancer therapy. Once internalized by 4T1 cells, the outer ZIF-8 was rapidly degraded to trigger the release of CuS nanoparticles (NPs), which could react with local GSH and sequentially hydrogen peroxide (H2O2) to form hydroxyl radical (·OH) for CDT. More importantly, the hyperthermia generated by APCZ upon 1064 nm laser excitation not only permitted NIR-II photothermal therapy (PTT) and promoted CDT, but also triggered the decomposition of AIPH to give toxic alkyl radical (·R) for oxygen-independent PDT. Besides, the PDA together with CuS greatly decreased the GSH level and resulted in significantly enhanced PDT/CDT in both normoxic and hypoxic conditions. The tumors could be completely eradicated after 14 days of treatment due to the prominent therapeutic effects of PTT/PDT/CDT. Additionally, the feasibility of APCZ as a photoacoustic (PA) imaging contrast agent was also demonstrated.ConclusionsThe novel APCZ could realize the cooperative amplification effect of free radicals-based therapies by NIR-II light excitation and GSH consumption, and act as a contrast agent to improve PA imaging, holding tremendous potential for efficient diagnosis and treatment of deep-seated and hypoxic tumors.Graphic abstract

Multiple cooperative amplification paper SERS aptasensor based on AuNPs/3D succulent-like silver for okadaic acid quantization

Okadaic acid (OA) is the main toxic component of diarrhetic shellfish poisoning, which can cause vomiting, diarrhea, and even induce tumor formation in people who accidentally ingest it. To strengthen the front-end prevention and control of shellfish safety, a surface-enhanced Raman scattering (SERS) paper swab based on high-affinity binding and high-specific recognition performance of nucleic acid aptamer was proposed to detect OA by virtue of enhanced multistage plasmon coupling effect. Composite resonance bilayer constituted by evenly dispersed gold nanoparticles integrating with a three-dimensional (3D) succulent-like silver particle was facilely manufactured in-situ on the paper substrate. Subsequently, with the assistance of 3D nanotopography structured silver nano-octahedra connected on the signal probe, a multistage SERS signal cooperative amplification platform was formed with about 10-fold enhanced Raman intensity higher than either single-layer substrate. Owning to the unique strategy of superimposed signal enhancement, such paper SERS aptasensor possessed admirable specific recognition and sensitivity has been successfully used in the on-site quantization of OA, with a detection limit of 0.31 ng/mL. Furthermore, the construction of the SERS paper swab is of great significance to the promotion of rapid on-site analysis approach of OA content in seafood by customs, seafood market supervision departments and ordinary consumers.

Target-triggered signal-on ratiometric electrochemiluminescence sensing of PSA based on MOF/Au/G-quadruplex

Signal-amplified ratiometric electrochemiluminescence (Sa-RECL) provides an attractive approach to maximize signal-to-noise ratio through enhancing signals and eliminate interferences. In this work, we prepared a novel metal-organic framework (MOF)/Au/G-quadruplex as both quenchers and enhancers to fabricate a target-triggered ratiometric ECL sensor for high sensitive and accurate detection of prostatic specific antigen (PSA). The ratiometric ECL sensor using the dual-potential-dependent ECL emitters (quantum dots (QDs) and luminol) and MOF/Au/G-quadruplex not only achieved signal self-calibration but also realized cooperative amplification. After the sequential hybridization among of complementary DNA-QDs, PSA aptamer and pDNA-Au-Hemin-MIL-DNAzyme and the further competition of PSA, the pDNA-Au-Hemin-MIL-DNAzyme probe would keep away from the electrode surface, causing a switchover of their ECL signals from “off-on” state to “on-off” state. The ratiometric ECL aptasensor exhibits high-sensitive and accurate analytical performance toward PSA with a linear detection range from 0.5 to 500 ng mL−1 and a detection limit of 0.058 ng mL−1 (S/N = 3). The novel ratiometric ECL biosensor has been successfully applied to determine different serum samples of PSA, indicating its potential application in the clinical diagnosis.

Low Cost and Reliable Electrochemical Sensor for Rutin Detection Based on Au Nanoparticles-Loaded ZnS Nanocomposites.

Facile preparation of electrode modified materials with low-cost nanocomposites is an important step to develop highly active electrochemical sensors for mass-market applications. Here we fabricated Au nanoparticles (AuNPs)-loaded ZnS nanocomposites for the sensitive determination of rutin due to the cooperative amplification of the conductivity and catalytic activity of AuNPs on ZnS spheres resulting from the high loading ratio of AuNPs on ZnS spheres. Under the optimal conditions, the developed sensor based on AuNPs-loaded ZnS nanocomposites exhibited excellent electrocatalytic activity towards rutin in a linear range from 1 × 10-7 mol/L to 2 × 10-5 mol/L with a limit of detection of 15.3 nM at a signal-to-noise ratio of 3. Furthermore, the proposed method gave satisfactory results for rutin determination in pharmaceutical tablets, which offer promising potential for rutin electrochemical analysis in serum monitoring or Chinese medical analysis owing to its simplicity, low cost, high sensitivity and good stability.

Twisted Thiophene-Based Chromophores with Enhanced Intramolecular Charge Transfer for Cooperative Amplification of Third-Order Optical Nonlinearity.

Exploiting synergistic cooperation between multiple sources of optical nonlinearity, we report the design, synthesis, and nonlinear optical properties of a series of electron-rich thiophene-containing donor-acceptor chromophores with condensed π-systems and sterically regulated inter-aryl twist angles. These structures couple two key mechanisms underlying optical nonlinearity, namely, (i) intramolecular charge transfer, greatly enhanced by increased electron density and reduced aromaticity at chromophore thiophene rings and (ii) a twisted chromophore geometry, producing a manifold of close-lying excited states and dipole moment changes between ground and excited states that are nearly twice that of untwisted systems. Spectroscopic, electrochemical, and nonlinear Z-scan measurements, combined with quantum chemical calculations, illuminate relationships between molecular structure and mechanisms of enhancement of the nonlinear refractive index. Experiment and calculations together reveal ground-state structures that are strongly responsive to the solvent polarity, leading to substantial negative solvatochromism (Δλ ≈ 10(2) nm) and prevailing zwitterionic/aromatic structures in the solid state and in polar solvents. Ground-to-excited-state energy gaps below 2.0 eV are obtained in condensed π-systems, with lower energy gaps for twisted versus untwisted systems. The real part of the second hyperpolarizability in the twisted structures is much greater than the imaginary part, with the highest twist angle chromophore giving |Re(γ)/Im(γ)| ≈ 100, making such chromophores very promising for all-optical-switching applications.

Vitamin D and estrogen synergy in Vdr-expressing CD4+ T cells is essential to induce Helios+FoxP3+ T cells and prevent autoimmune demyelinating disease

Multiple sclerosis (MS) is a neurodegenerative disease resulting from an autoimmune attack on the axon-myelin unit. A female MS bias becomes evident after puberty and female incidence has tripled in the last half-century, implicating a female sex hormone interacting with a modifiable environmental factor. These aspects of MS suggest that many female MS cases may be preventable. Mechanistic knowledge of this hormone–environment interaction is needed to devise strategies to reduce female MS risk. We previously demonstrated that vitamin D3 (D3) deficiency increases and D3 supplementation decreases experimental autoimmune encephalomyelitis (EAE) risk in a female-biased manner. We also showed that D3 acts in an estrogen (E2)-dependent manner, since ovariectomy eliminated and E2 restored D3-mediated EAE protection. Here we probed the hypothesis that E2 and D3 interact synergistically within CD4+ T cells to control T cell fate and prevent demyelinating disease. The E2 increased EAE resistance in wild-type (WT) but not T-Vdr0 mice lacking Vdr gene function in CD4+ T cells, so E2 action depended entirely on Vdr+CD4+ T cells. The E2 levels were higher in WT than T-Vdr0 mice, suggesting the Vdr+CD4+ T cells produced E2 or stimulated its production. The E2 decreased Cyp24a1 and increased Vdr transcripts in T cells, prolonging the calcitriol half-life and increasing calcitriol responsiveness. The E2 also increased CD4+Helios+FoxP3+ T regulatory (Treg) cells in a Vdr-dependent manner. Thus, CD4+ T cells have a cooperative amplification loop involving E2 and calcitriol that promotes CD4+Helios+FoxP3+ Treg cell development and is disrupted when the D3 pathway is impaired. The global decline in population D3 status may be undermining a similar cooperative E2–D3 interaction controlling Treg cell differentiation in women, causing a breakdown in T cell self tolerance and a rise in MS incidence.

Hairpin assembly circuit-based fluorescence cooperative amplification strategy for enzyme-free and label-free detection of small molecule

Here, we developed an enzyme-free, label-free, and sensitive fluorescence cooperative amplification strategy based on a hairpin assembly circuit which coupled catalytic hairpin assembly (CHA) with hybridization chain reaction (HCR) for small molecule adenosine. A double-strand DNA probe with aptamer-catalysis strand (Apt-C) and inhibit strand (Inh) was designed for adenosine recognition and signal transduction which was named as Apt-C/Inh. Hairpins H1 and H2 were employed for constructing the CHA, and hairpins H3 and H4 for the HCR. Through the binding of adenosine and the Apt-C, the Inh was released from the Apt-C/Inh. Then the free Apt-C initiated the CHA through successively opening H1 and H2, generating H1/H2 complex and recyclable Apt-C. Next, the released Apt-C entered another CHA cycle, and the H1/H2 complex further initiated the HCR of H3 and H4 which induced the formation of the concatemers of H3/H4 complex. Such a process brought the two ends of hairpins H3 into close proximity, yielding numerous integrated G-quadruplexes which were initially sequestered in the stem and two terminals of H3. Finally, N-methyl mesoporphyrin IX (NMM) was added to generate an enhanced fluorescence signal. In the proposed strategy, driven only by the energy from hybridization, one target could trigger multiple HCR events via CHA-based target-cycle, leading to a remarkable enzyme-free amplification for adenosine. The detection limit could achieve as low as 9.7 × 10−7molL−1. Furthermore, G-quadruplexes were applied to construct label-free hairpin assembly circuit, which made it more simple and cost-effective. The satisfactory recoveries were obtained when detecting adenosine in spiked human serum and urine samples, demonstrating the feasibility of this detection strategy in biological samples.

Energy transfer in plasmonic systems

We present our results on energy transfer between donor and acceptor molecules or quantum dots near a plasmonic nanoparticle. In such systems, the Förster resonance energy transfer is strongly modified due to plasmon-mediated coupling between donors and acceptors. The transfer efficiency is determined by a competition between transfer, radiation and dissipation that depends sensitively on system parameters. When donor and accepror spectral bands overlap with dipole surface plasmon resonance, the dominant transfer mechanism is through plasmon-enhanced radiative coupling. When transfer takes place from an ensemble of donors to an acceptor, a cooperative amplification of energy transfer takes place in a wide range of system parameters.

Graphene fluorescence switch-based cooperative amplification: a sensitive and accurate method to detection microRNA.

MicroRNAs (miRNAs) play significant roles in a diverse range of biological progress and have been regarded as biomarkers and therapeutic targets in cancer treatment. Sensitive and accurate detection of miRNAs is crucial for better understanding their roles in cancer cells and further validating their function in clinical diagnosis. Here, we developed a stable, sensitive, and specific miRNAs detection method on the basis of cooperative amplification combining with the graphene oxide (GO) fluorescence switch-based circular exponential amplification and the multimolecules labeling of SYBR Green I (SG). First, the target miRNA is adsorbed on the surface of GO, which can protect the miRNA from enzyme digest. Next, the miRNA hybridizes with a partial hairpin probe and then acts as a primer to initiate a strand displacement reaction to form a complete duplex. Finally, under the action of nicking enzyme, universal DNA fragments are released and used as triggers to initiate next reaction cycle, constituting a new circular exponential amplification. In the proposed strategy, a small amount of target miRNA can be converted to a large number of stable DNA triggers, leading to a remarkable amplification for the target. Moreover, compared with labeling with a 1:1 stoichiometric ratio, multimolecules binding of intercalating dye SG to double-stranded DNA (dsDNA) can induce significant enhancement of fluorescence signal and further improve the detection sensitivity. The extraordinary fluorescence quenching of GO used here guarantees the high signal-to-noise ratio. Due to the protection for target miRNA by GO, the cooperative amplification, and low fluorescence background, sensitive and accurate detection of miRNAs has been achieved. The strategy proposed here will offer a new approach for reliable quantification of miRNAs in medical research and early clinical diagnostics.

Cooperative amplification of energy transfer in plasmonic systems

We study cooperative effects in energy transfer (ET) from an ensemble of donors to an acceptor near a plasmonic nanostructure. We demonstrate that in cooperative regime ET takes place from plasmonic superradiant and subradiant states rather than from individual donors leading to a significant increase of ET efficiency. The cooperative amplification of ET relies on the large coupling of superradiant states to external fields and on the slow decay rate of subradiant states. We show that superradiant and subradiant ET mechanisms are efficient in different energy domains and therefore can be utilized independently. We present numerical results demonstrating the amplification effect for a layer of donors and an acceptor on a spherical plasmonic nanoparticle.

Control of layer 5 pyramidal cell spiking by oscillatory inhibition in the distal apical dendrites: a computational modeling study

The distal apical dendrites of layer 5 pyramidal neurons receive cortico-cortical and thalamocortical top-down and feedback inputs, as well as local recurrent inputs. A prominent source of recurrent inhibition in the neocortical circuit is somatostatin-positive Martinotti cells, which preferentially target distal apical dendrites of pyramidal cells. These electrically coupled cells can fire synchronously at various frequencies, including over a relatively slow range (5∼30 Hz), thereby imposing oscillatory inhibition on the pyramidal apical tuft dendrites. We examined how such distal oscillatory inhibition influences the firing of a biophysically detailed layer 5 pyramidal neuron model, which reproduced the spatiotemporal properties of sodium, calcium, and N-methyl-D-aspartate receptor spikes found experimentally. We found that oscillatory synchronization strongly influences the impact of distal inhibition on the pyramidal cell firing. Whereas asynchronous inhibition largely cancels out the facilitatory effects of distal excitatory inputs, inhibition oscillating synchronously at around 10∼20 Hz allows distal excitation to drive axosomatic firing, as if distal inhibition were absent. Underlying this is a switch from relatively infrequent burst firing to single spike firing at every period of the inhibitory oscillation. This phenomenon depends on hyperpolarization-activated cation current-dependent membrane potential resonance in the dendrite, but also, in a novel manner, on a cooperative amplification of this resonance by N-methyl-D-aspartate-receptor-driven dendritic action potentials. Our results point to a surprising dependence of the effect of recurrent inhibition by Martinotti cells on their oscillatory synchronization, which may control not only the local circuit activity, but also how it is transmitted to and decoded by downstream circuits.

Cooperative decay rate and cooperative Lamb shift from a nanospherical configuration of two adjoining atomic species

The eigenmodes of a nanosphere configuration where the core is an ensemble of two-level atoms with resonance frequency ${\ensuremath{\omega}}_{C}$, and the shell is an ensemble of two-level atoms but with shifted resonant frequency ${\ensuremath{\omega}}_{B}$ are obtained for different values of the ratio of the core radius to the shell outer radius as function of $({\ensuremath{\omega}}_{C}\ensuremath{-}{\ensuremath{\omega}}_{B})$. I show that the eigenmodes belong to one of two branches. The dominant decay mode for superradiant emission may belong to either branch, depending on the system's parameters. In instances of configurations where the cooperative decay rate values for the two branches become equal, the cooperative exponential amplification (decay) is accompanied by temporal oscillations.

Preferences of transmembrane helices for cooperative amplification of G(alpha)s and G (alpha)q signaling of the thyrotropin receptor.

The majority of constitutively activating mutations (CAMs) of the thyroid-stimulating hormone receptor display a partially activated receptor. Thus, full receptor activation requires a multiplex activation process. To define impacts of different transmembrane helices (TMHs) on cooperative signal transduction, we combined single CAMs in particular TMHs to double mutations and measured second messenger accumulation of the G(alpha)s and the G(alpha)q pathway. We observed a synergistic increase for basal activity of the G(alpha)s pathway, for all characterized double mutants except for two combinations. Each double mutation, containing CAMs in TMH2, 6 and 7 showed the highest constitutive activities, suggesting that these helices contribute most to G(alpha)s-mediated signaling. No single CAM revealed constitutive activity for the G(alpha)q pathway. The double mutations with CAMs from TMH1, 2, 3 and 6 also exhibited increase for basal G(alpha)q signaling. Our results suggest that TMH2, 6, 7 show selective preferences towards G(alpha)s signaling, and TMH1, 2, 3, 6 for G(alpha)q signaling.

Cooperative C-F...Si interaction in optically active helical polysilanes.

Cooperative amplification of the C-F...Si weak interaction between side chains and the main chain was found to afford rigid rodlike helical polysilanes with a preferential screw sense.