Quantum Synchronization in Presence of Shot Noise

Synchronization is a widespread phenomenon encountered in many natural and engineered systems with nonlinear classical dynamics. How synchronization concepts and mechanisms transfer to the quantum realm and whether features are universal or platform specific are timely questions of fundamental interest. Here, we present a new approach to model incoherently driven dissipative quantum systems susceptible to synchronization within the framework of Josephson photonics devices, where a dc-biased Josephson junction creates (non-classical) light in a microwave cavity. The combined quantum compound constitutes a self-sustained oscillator with a neutrally stable phase. Linking current noise to the full counting statistics of photon emission allows us to capture phase diffusion, but moreover permits phase locking to an ac-signal and mutual synchronization of two such devices. Thereby one can observe phase stabilization leading to a sharp emission spectrum as well as unique photon emission statistics revealing shot noise induced phase slips. Two-time perturbation theory is used to obtain a reduced description of the oscillators phase dynamics in form of a Fokker-Planck equation in generalization of classical synchronization theories.Comment: 14 pages, 10 figure

New Role for L-Arginine in Regulation of Inducible Nitric-Oxide-Synthase-Derived Superoxide Anion Production in Raw 264.7 Macrophages

Dietary supplementation with L-arginine was shown to improve immune responses in various inflammatory models. However, the molecular mechanisms underlying L-arginine effects on immune cells remain unrecognized. Herein, we tested the hypothesis that a limitation of L-arginine could lead to the uncoupled state of murine macrophage inducible nitric oxide synthase and, therefore, increase inducible nitric-oxide-synthase-derived superoxide anion formation. Importantly, we demonstrated that L-arginine dose- and time dependently potentiated superoxide anion production in bacterial endotoxin-stimulated macrophages, although it did not influence NADPH oxidase expression and activity. Detailed analysis of macrophage activation showed the time dependence between LPS-induced iNOS expression and increased O2∙− formation. Moreover, downregulation of macrophage iNOS expression, as well as the inhibition of iNOS activity by NOS inhibitors, unveiled an important role of this enzyme in controlling O2∙− and peroxynitrite formation during macrophage stimulation. In conclusion, our data demonstrated that simultaneous induction of NADPH oxidase, together with the iNOS enzyme, can result in the uncoupled state of iNOS resulting in the production of functionally important levels of O2∙− soon after macrophage activation with LPS. Moreover, we demonstrated, for the first time that increased concentrations of L-arginine further potentiate iNOS-dependent O2∙− formation in inflammatory macrophages

An Effective Translation: The Development of Hyaluronan-Based Medical Products From the Physicochemical, and Preclinical Aspects

This review shows the steps toward material selection focalized on the design and development of medical devices based on hyaluronan (HA). The selection is based on chemical and mechanical properties, biocompatibility, sterilization, safety, and scale-up costs. These facts play a vital role in the industrialization process. Approved medical devices containing-HA are illustrated to identify key parameters. The first part of this work involves the steps toward a complete characterization of chemical and mechanical aspects, reproducibility of the processes and scale up. In a second stage, we aimed to describe the preclinical in vitro and in vivo assays and selected examples of clinical trials. Furthermore, it is important to keep in mind the regulatory affairs during the research and development (R&D) using standardization (ISO standards) to achieve the main goal, which is the functionality and safety of the final device. To keep reproducible experimental data to prepare an efficient master file for the device, based on quality and recorded manufacturing data, and a rigorous R&D process may help toward clinical translation. A strong debate is still going on because the denominated basic research in HA field does not pay attention to the purity and quality of the raw materials used during the development. So that, to achieve the next generation of devices is needed to overcome the limitations of state of art in terms of efficacy, biodegradability, and non-toxicity

The Potency of Hyaluronan of Different Molecular Weights in the Stimulation of Blood Phagocytes

The regulatory functions of glycosaminoglycan hyaluronan (HA) are suggested to be dependent on its molecular weight (MW). Proinflammatory and stimulatory effects are proposed mainly for the low MW HA. However, the complex response of blood phagocytes to HA of different MW is unclear. Herein, the effects of highly purified HA of precisely defined MW (52, 250, and 970 kDa) on human blood phagocytes were tested. All MW HA activated blood phagocytes, including the spontaneous production of ROS, degranulation, and the production of tumor necrosis factor alpha, with low MW HA 52 kDa having the highest potency and high MW HA 970 kDa having the lowest potency. Interestingly, HA inhibited ROS production stimulated by opsonized zymosan particles and, in contrast, potentiated starch-activated ROS production, mostly independent of MW. Data showed a significant effect of HA of different MW on blood phagocytes, including high MW HA

Pseurotin D Inhibits the Activation of Human Lymphocytes

Background: Pseurotins, a family of secondary metabolites of different fungi characterized by an unusual spirocyclic furanone-lactam core, are suggested to have different biological activities including the modulation of immune response. Purpose: Complex characterization of the effects of pseurotin D on human lymphocyte activation in order to understand the potential of pseurotin to modulate immune response in humans. Methods: CD4+ and CD8+ T cells and CD19+ B cells isolated from human blood were activated by various activators simultaneously with pseurotin D treatment. The effects of pseurotin were tested on the basis of changes in cell viability, apoptosis, activation of signal transducers and activators of transcription (STAT) signaling pathways, production of tumor necrosis factor (TNF)-α by T cells, expression of activation markers CD69 and CD25 on T cells and Human Leukocyte Antigen–DR isotype (HLA-DR) on B cells, and the differentiation markers CD20, CD27, CD38, and immunoglobulin (Ig) D on B cells. Results: Pseurotin D significantly inhibited the activation of both CD4+ and CD8+ human T cells complemented by the inhibition of TNF-α production without significant acute toxic effects. The Pseurotin D-mediated inhibition of T-cell activation was accompanied by the induction of the apoptosis of T cells. This corresponded with the inhibited phosphorylation of STAT3 and STAT5. In human B cells, pseurotin D did not significantly inhibit their activation; however, it affected their differentiation. Conclusions: Our results advance the current mechanistic understanding of the pseurotin-induced inhibition of lymphocytes and suggest pseurotins as new attractive chemotypes for future research in the context of immune-modulatory drugs

Injection locking and synchronization in Josephson photonics devices

Injection locking can stabilize a source of radiation, leading to an efficient suppression of noise-induced spectral broadening and therefore, to a narrow spectrum. The technique is well established in laser physics, where a phenomenological description due to Adler is usually sufficient. Recently, locking experiments were performed in Josephson photonics devices, where microwave radiation is created by inelastic Cooper pair tunneling across a dc-biased Josephson junction connected in-series with a microwave resonator. An in-depth theory of locking for such devices, accounting for the Josephson nonlinearity and the specific engineered environments, is lacking. Here, we study injection locking in a typical Josephson photonics device where the environment consists of a single mode cavity, operated in the classical regime. We show that an in-series resistance, however small, is an important ingredient in describing self-sustained Josephson oscillations and enables the locking region. We derive a dynamical equation describing locking, similar to an Adler equation, from the specific circuit equations. The effect of noise on the locked Josephson phase is described in terms of phase slips in a modified washboard potential. For weak noise, the spectral broadening is reduced exponentially with the injection signal. When this signal is provided from a second Josephson device, the two devices synchronize. In the linearized limit, we recover the Kuramoto model of synchronized oscillators. The picture of classical phase slips established here suggests a natural extension towards a theory of locking in the quantum regime

The reverse tetracycline-controlled transactivator rtTA2S^{\rm S}-S2 is toxic in mouse embryonic stem cells

The efficient and reversible control of transgene expression is a powerful tool for the correct manipulation of embryonic stem cells in both cell therapy and transgenesis. The aim of this work was to investigate the possibilities of recently developed reverse tetracycline-controlled transactivator rtTA2$^{\rm S}$-S2. We show that the rtTA2$^{\rm S}$-S2 is useful for transient inducible expression of genes in embryonic stem cells. However, we found that it was not possible to establish mouse embryonic stem cell lines stably expressing this transactivator. Using the viral IRES sequence which couples the expression of rtTA2$^{\rm S}$-S2 and neomycin phosphotransferase, we found that embryonic stem cells expressing rtTA2$^{\rm S}$-S2 are not capable of growing in the presence of G418. Our results indicate that this transactivator is toxic to ES cells and raise the need for the development of other strategies for stable and inducible expression of genes in ES cells

Synchronization in Josephson photonics devices in the presence of shot noise

For many quantum sources the exploitation and characterization of their quantum properties, such as entanglement and squeezing, is hampered by phase instability. Josephson photonics devices, where microwave radiation is created by inelastic Cooper pair tunneling across a dc-biased Josephson junction in-series with a microwave resonator are particularly vulnerable lacking the reference phase provided by an ac-drive. To counter this issue, sophisticated measurement schemes have been used in [1] to prove entanglement, while in [2] a weak ac-signal was put in to lock phase and frequency of the emission. Intrinsic shot noise of the Josephson-photonics device inevitably diffuses the oscillators phase and requires an extension of classical synchronization theories to the quantum regime. Performing multi-time scale perturbation theory we derive an effective Fokker-Plank equation for the phase to analyze quantum locking and synchronization in an Adler-type equation. Injection locking and synchronization lead to a narrowing of the photon emission statistics, while the shot noise induces phase slips. [1] A. Peugeot et al., Phys. Rev. X 11, 031008 (2021). [2] M. C. Cassidy et al., Science 355, 939 (2017)