Kisspeptin is encoded by the Kiss1 gene, and kisspeptin signaling plays a critical role in reproduction. In rodents, kisspeptin neurons in the arcuate nucleus (Arc) provide tonic drive to gonadotropin-releasing hormone (GnRH) neurons, which in turn supports basal luteinizing hormone (LH) secretion. Our objectives were to determine whether preprodynorphin (Dyn) and neurokinin B (NKB) are coexpressed in Kiss1 neurons in the mouse and to evaluate its physiological significance. Using in situ hybridization, we found that Kiss1 neurons in the Arc of female mice not only express the Dyn and NKB genes but also the NKB receptor gene (NK3) and the Dyn receptor [the κ opioid receptor (KOR)] gene. We also found that expression of the Dyn, NKB, KOR, and NK3 in the Arc are inhibited by estradiol, as has been established for Kiss1, and confirmed that Dyn and NKB inhibit LH secretion. Moreover, using Dyn and KOR knock-out mice, we found that long-term disruption of Dyn/KOR signaling compromises the rise of LH after ovariectomy. We propose a model whereby NKB and dynorphin act autosynaptically on kisspeptin neurons in the Arc to synchronize and shape the pulsatile secretion of kisspeptin and drive the release of GnRH from fibers in the median eminence.
Two-dimensional ideal incompressible magnetohydrodynamic (MHD) linear waves at the surface of a rotating sphere are studied as a model to imitate the outermost layer of the Earth's core or the solar tachocline. This thin conducting layer is permeated by a toroidal magnetic field the magnitude of which depends only on the latitude. The Malkus background field, which is proportional to the sine of the colatitude, provides two well-known groups of branches; on one branch, retrograde Alfvén waves gradually become fast magnetic Rossby (MR) waves as the field amplitude decreases, and on the other, prograde Alfvén waves undergo a gradual transition into slow MR waves. In the case of non-Malkus fields, we demonstrate that the associated eigenvalue problems can yield a continuous spectrum instead of Alfvén and slow MR discrete modes. The critical latitudes attributed to the Alfvén resonance eliminate these discrete eigenvalues and produce an infinite number of singular eigenmodes. The theory of slowly varying wave trains in an inhomogeneous magnetic field shows that a wave packet related to this continuous spectrum propagates toward a critical latitude corresponding to the wave and is eventually absorbed there. The expected behaviour whereby the retrograde propagating packets pertaining to the continuous spectrum approach the latitudes from the equatorial side and the prograde ones approach from the polar side is consistent with the profiles of their eigenfunctions derived using our numerical calculations. Further in-depth discussions of the Alfvén continuum would develop the theory of the ``wave-mean field interaction'' in the MHD system and the understanding of the dynamics in such thin layers.
Abstract The research of dynamic community detection is becoming increasingly popular since it can disclose how the community structures change over time in dynamic networks. Evolutionary clustering is often utilized for the goal and has achieved some success, which, however, still has some major drawbacks: (1) The absence of error correction may lead to the result-drifting problem and the error accumulation problem; (2) The NP-hardness of modularity based community detection makes it low efficiency to get an exact solution. In this paper, an efficient and effective multi-objective method, namely DYN-MODPSO, is proposed, and where the traditional evolutionary clustering framework and the particle swarm algorithm are modified and enhanced, respectively. The main contributions include that: (1) A novel strategy, namely the recent future reference, is devised for the initial clustering result correction to make the dynamic community detection more effective; (2) The traditional particle swarm algorithm is improved and integrated with the evolutionary clustering framework by profitably exploiting the proposed strategy; (3) The de-redundant random walk based population initialization is proposed to diversify the individuals in a quality-guaranteed way. Furthermore, the multi-individual crossover operator and the improved interference operator are carefully designed to keep the solution from local optimization. Extensive experiments conducted on the real and the synthetic dynamic networks manifest that the proposed DYN-MODPSO outperforms the competitors in terms of both effectiveness and efficiency.
BACKGROUND While there is high comorbidity of stress-related disorders and alcohol use disorder, few effective treatments are available and elucidating underlying neurobiological mechanisms has been hampered by a general lack of reliable animal models. Here, we use a novel mouse model demonstrating robust and reproducible stress-enhanced alcohol drinking to examine the role of dynorphin/kappa opioid receptor (DYN/KOR) activity within the extended amygdala in mediating this stress-alcohol interaction. METHODS Mice received repeated weekly cycles of chronic intermittent ethanol exposure alternating with weekly drinking sessions ± forced swim stress exposure. Pdyn messenger RNA expression was measured in the central amygdala (CeA), and DYN-expressing CeA neurons were then targeted for chemogenetic inhibition. Finally, a KOR antagonist was microinjected into the CeA or bed nucleus of the stria terminalis to examine the role of KOR signaling in promoting stress-enhanced drinking. RESULTS Stress (forced swim stress) selectively increased alcohol drinking in mice with a history of chronic intermittent ethanol exposure, and this was accompanied by elevated Pdyn messenger RNA levels in the CeA. Targeted chemogenetic silencing of DYN-expressing CeA neurons blocked stress-enhanced drinking, and KOR antagonism in the CeA or bed nucleus of the stria terminalis significantly reduced stress-induced elevated alcohol consumption without altering moderate intake in control mice. CONCLUSIONS Using a novel and robust model of stress-enhanced alcohol drinking, a significant role for DYN/KOR activity within extended amygdala circuitry in mediating this effect was demonstrated, thereby providing further evidence that the DYN/KOR system may be a valuable target in the development of more effective treatments for individuals presenting with comorbidity of stress-related disorders and alcohol use disorder.
Quipper is a functional programming language for quantum computing. Proto-Quipper is a family of languages aiming to provide a formal foundation for Quipper. In this paper, we extend Proto-Quipper-M with a construct called dynamic lifting, which is present in Quipper. By virtue of being a circuit description language, Proto-Quipper has two separate runtimes: circuit generation time and circuit execution time. Values that are known at circuit generation time are called parameters, and values that are known at circuit execution time are called states. Dynamic lifting is an operation that enables a state, such as the result of a measurement, to be lifted to a parameter, where it can influence the generation of the next portion of the circuit. As a result, dynamic lifting enables Proto-Quipper programs to interleave classical and quantum computation. We describe the syntax of a language we call Proto-Quipper-Dyn. Its type system uses a system of modalities to keep track of the use of dynamic lifting. We also provide an operational semantics, as well as an abstract categorical semantics for dynamic lifting based on enriched category theory. We prove that both the type system and the operational semantics are sound with respect to our categorical semantics. Finally, we give some examples of Proto-Quipper-Dyn programs that make essential use of dynamic lifting.
Substance use disorders (SUD) may emerge from an individual’s attempt to limit negative affective states and symptoms linked to stress. Indeed, SUD is highly comorbid with chronic stress, traumatic stress, or post-traumatic stress disorder (PTSD), and treatments approved for each pathology individually often failed to have a therapeutic efficiency in such comorbid patients. The kappa-opioid receptor (KOR) and its endogenous ligand dynorphin (DYN), seem to play a key role in the occurrence of this comorbidity. The DYN/KOR function is increased either in traumatic stress or during drug use, dependence acquisition and DYN is released during stress. The behavioural effects of stress related to the DYN/KOR system include anxiety, dissociative and depressive symptoms, as well as increased conditioned fear response. Furthermore, the DYN/KOR system is implicated in negative reinforcement after the euphoric effects of a drug of abuse ends. During chronic drug consumption DYN/KOR functions increase and facilitate tolerance and dependence. The drug-seeking behaviour induced by KOR activation can be retrieved either during the development of an addictive behaviour, or during relapse after withdrawal. DYN is known to be one of the most powerful negative modulators of dopamine signalling, notably in brain structures implicated in both reward and fear circuitries. KOR are also acting as inhibitory heteroreceptors on serotonin neurons. Moreover, the DYN/KOR system cross-regulate with corticotropin-releasing factor in the brain. The sexual dimorphism of the DYN/KOR system could be the cause of the gender differences observed in patients with SUD or/and traumatic stress-related pathologies. This review underlies experimental and clinical results emphasizing the DYN/KOR system as common mechanisms shared by SUD or/and traumatic stress-related pathologies, and suggests KOR antagonist as a new pharmacological strategy to treat this comorbidity.
Metastasis represents a dynamic succession of events involving tumor cells which disseminate through the organism via the bloodstream. Circulating tumor cells (CTCs) can flow the bloodstream as single cells or as multicellular aggregates (clusters), which present a different potential to metastasize. The effects of the bloodstream-related physical constraints, such as hemodynamic wall shear stress (WSS), on CTC clusters are still unclear. Therefore, we developed, upon theoretical and CFD modeling, a new multichannel microfluidic device able to simultaneously reproduce different WSS characterizing the human circulatory system, where to analyze the correlation between SS and CTC clusters behavior. Three physiological WSS levels (i.e. 2, 5, 20 dyn/cm2) were generated, reproducing values typical of capillaries, veins and arteries. As first validation, triple-negative breast cancer cells (MDA-MB-231) were injected as single CTCs showing that higher values of WSS are correlated with a decreased viability. Next, the SS-mediated disaggregation of CTC clusters was computationally investigated in a vessels-mimicking domain. Finally, CTC clusters were injected within the three different circuits and subjected to the three different WSS, revealing that increasing WSS levels are associated with a raising clusters disaggregation after 6 hours of circulation. These results suggest that our device may represent a valid in vitro tool to carry out systematic studies on the biological significance of blood flow mechanical forces and eventually to promote new strategies for anticancer therapy.
Wenwei Wu, Francois G. Schmitt, Enrico Calzavarini
et al.
We study the three-dimensional turbulent Kolmogorov flow, i.e. the Navier-Stokes equations forced by a low-single-wave-number sinusoidal force in a periodic domain, by means of direct numerical simulations. This classical model system is a realization of anisotropic and non-homogeneous hydrodynamic turbulence. Boussinesq's eddy viscosity linear relation is checked and found to be approximately valid over half of the system volume. A more general nonlinear quadratic Reynolds stress development is proposed and its parameters estimated at varying the Taylor scale-based Reynolds number in the flow up to the value 200. The case of a forcing with a different shape, here chosen Gaussian, is considered and the differences with the sinusoidal forcing are emphasized.
Sneha Srikanth, Ankit Sahay, Samadhan A. Pawar
et al.
The presence of undesirable large-amplitude self-sustained oscillations in combustors resulting from thermoacoustic instability can lead to performance loss and structural damage to components of gas turbine and rocket engines. Traditional feedback controls to mitigate thermoacoustic instability possess electromechanical components, which are expensive to maintain regularly and unreliable in the harsh environments of combustors. In this study, we demonstrate the quenching of thermoacoustic instability through self-coupling -- a method wherein a hollow tube is used to provide acoustic self-feedback to a thermoacoustic system. Through experiments and modeling, we identify the optimal coupling conditions for attaining amplitude death, i.e., complete suppression of thermoacoustic instabilities, in a horizontal Rijke tube. We examine the effect of both system and coupling parameters on the occurrence of amplitude death. We thereby show that the parametric regions of amplitude death occur when the coupling tube length is close to an odd multiple of the length of the Rijke tube. The optimal location of the coupling tube for achieving amplitude death is near the anti-node of the acoustic standing wave in the Rijke tube. Furthermore, we find that self-coupling mitigates thermoacoustic instability in a Rijke tube more effectively than mutual coupling of two identical Rijke tubes. Thus, we believe that self-coupling can prove to be a simple, cost-effective solution for mitigating thermoacoustic instability in gas turbine combustors.
Clodoaldo Ragazzo, Gwenaël Boué, Yeva Gevorgyan
et al.
We present fully three-dimensional equations to describe the rotations of a body made of a deformable mantle and a fluid core. The model in its essence is similar to that used by INPOP (Integration Planétaire de l'Observatoire de Paris), e.g. Viswanathan et al. (2019), and by JPL (Jet Propulsion Laboratory), e.g. Folkner et al. (2014), to represent the Moon. The intended advantages of our model are: straightforward use of any linear-viscoelastic model for the rheology of the mantle; easy numerical implementation in time-domain (no time lags are necessary); all parameters, including those related to the "permanent deformation", have a physical interpretation. The paper also contains: 1) A physical model to explain the usual lack of hydrostaticity of the mantle (permanent deformation). 2) Formulas for free librations of bodies in and out-of spin-orbit resonance that are valid for any linear viscoelastic rheology of the mantle. 3) Formulas for the offset between the mantle and the idealized rigid-body motion (Peale's Cassini states). 4) Applications to the librations of Moon, Earth, and Mercury that are used for model validation.
Circuit-specific signaling of ventral tegmental area (VTA) dopamine neurons drives different aspects of motivated behavior, but the neuromodulatory control of these circuits is unclear. We tested the actions of co-expressed lateral hypothalamic peptides, orexin A (oxA) and dynorphin (dyn), on projection-target-defined dopamine neurons in mice. We determined that VTA dopamine neurons that project to the nucleus accumbens lateral shell (lAcbSh), medial shell (mAcbSh), and basolateral amygdala (BLA) are largely non-overlapping cell populations with different electrophysiological properties. Moreover, the neuromodulatory effects of oxA and dyn on these three projections differed. OxA selectively increased firing in lAcbSh- and mAcbSh-projecting dopamine neurons. Dyn decreased firing in the majority of mAcbSh- and BLA-projecting dopamine neurons but reduced firing only in a small fraction of those that project to the lAcbSh. In conclusion, the oxA-dyn input to the VTA may drive reward-seeking behavior by tuning dopaminergic output in a projection-target-dependent manner.
Moist processes are among the most important drivers of atmospheric dynamics,and scale analysis and asymptotics are cornerstones of theoretical meteorology. Accounting for moist processes in systematic scale analyses therefore seems of considerable importance for the field. Klein & Majda (TCFD, 20, 525--552, (2006)) proposed a scaling regime for the incorporation of moist bulk microphysics closures in multiscale asymptotic analyses of tropical deep convection. This regime is refined here to allow for mixtures of ideal gases and to establish consistency with a more general multiple scales modelling framework for atmospheric flows. Deep narrow updrafts, so-called "hot towers", constitute principal building blocks of larger scale storm systems. They are analysed here in a sample application of the new scaling regime. A single quasi-onedimensional columnar cloud is considered on the vertical advective (or tower life cycle) time scale. The refined asymptotic scaling regime is essential for this example as it reveals a new mechanism for the self-sustainance of such updrafts. Even for strongly positive convectively available potential energy (CAPE), a vertical balance of buoyancy forces is found in the presence of precipitation. This balance induces a diagnostic equation for the vertical velocity and it is responsible for the generation of self-sustained balanced updrafts. The time dependent updraft structure is encoded in a Hamilton-Jacobi equation for the precipitation mixing ratio. Numerical solutions of this equation suggest that the self-sustained updrafts may strongly enhance hot tower life cycles.
We present a high-resolution convergence study of detonation initiated by a temperature gradient in a stoichiometric hydrogen-oxygen mixture using the Pencil Code and compare with a code that employs a fifth order weighted essentially non-oscillating (WENO) scheme. With Mach numbers reaching 10-30, a certain amount of shock viscosity is needed in the Pencil Code to remove or reduce numerical pressure oscillations on the grid scale at the position of the shock. Detonation is found to occur for intermediate values of the shock viscosity parameter. At fixed values of this parameter, the numerical error associated with those small wiggles in the pressure profile is found to decrease with decreasing mesh width $δx$ like $δx^{-1.4}$ down to $δx=0.2μ$m. With the WENO scheme, solutions are smooth at $δx=10μ$m, but no detonation is obtained for $δx=5μ$m. This is argued to be an artifact of a decoupling between pressure and reaction fronts.