Independent control of amplitude and period in a synthetic oscillator circuit with modified repressilator

Synthetic Biology aims to create predictable biological circuits and fully operational biological systems. Although there are methods to create more stable oscillators, such as repressilators, independently controlling the oscillation of reporter genes in terms of their amplitude and period is only on theoretical level. Here, we introduce a new oscillator circuit that can be independently controlled by two inducers in Escherichia coli. Some control components, including σECF11 and NahR, were added to the circuit. By systematically tuning the concentration of the inducers, salicylate and IPTG, the amplitude and period can be modulated independently. Furthermore, we constructed a quantitative model to forecast the regulation results. Under the guidance of the model, the expected oscillation can be regulated by choosing the proper concentration combinations of inducers. In summary, our work achieved independent control of the oscillator circuit, which allows the oscillator to be modularized and used in more complex circuit designs.

Ultrathin Spin-Decoupled Meta-Devices for Independent Control of Electromagnetic Waves With Dual-Orthogonal Circular Polarization

Inspired by the concept of miniaturized and integrated systems, an ultrathin and multifunctional metasurface device is highly desirable in microwave fields. It is an inherent characteristic that the two spin phase states of electromagnetic waves imparted by the geometric phase are always conjugate symmetric, i.e., the geometric phase produces anti-symmetrical phase responses between dual-orthogonal circular polarization states. So it is extremely crucial to break the conjugate constraints and realize the completely independent control of electromagnetic waves with dual-orthogonal circular polarization. Based on this perspective, ultrathin and bifunctional meta-devices operating in reflection mode are proposed to independently manipulate the left-handed and right-handed circularly polarized waves, which are constructed by anisotropic meta-atoms with synthetical geometric and propagation phases. It is worth noting that the component elements only need a single-layer structure with the thickness of 0.07λ0. Several design samples are presented to achieve functionalities of beam focusing, vortex wave generation, and beam deflection, respectively. Experiments are performed and show good consistence with the simulation results, successfully verifying the performance of the designed metasurfaces. The research results in this paper pave the way to design low-profile and bifunctional devices with independent controls of circularly polarized waves, which is expected to expand the working capacity of metasurfaces to realize complex electromagnetic wave manipulation with a new degree of freedom.

IFN-γ-independent control of M. tuberculosis requires CD4 T cell-derived GM-CSF and activation of HIF-1α

The prevailing model of protective immunity to tuberculosis is that CD4 T cells produce the cytokine IFN-γ to activate bactericidal mechanisms in infected macrophages. Recent evidence has expanded this model, and it is now clear that CD4 T cells can control M. tuberculosis infection in the absence of IFN-γ production. To identify factors and pathways involved in IFN-γ-independent control, we developed a co-culture model using CD4 T cells isolated from the lungs of infected mice and M. tuberculosis-infected murine bone marrow-derived macrophages (BMDMs). We show that IFN-γ-independent control is primarily mediated by CD4 T cell production of the cytokine GM-CSF and requires activation of the macrophage transcription factor HIF-1α. HIF-1α activation drives a metabolic shift toward aerobic glycolysis and leads to the production of lipid droplets, both of which support host defense against infection. Surprisingly, recombinant GM-CSF is insufficient to rescue the absence of control by GM-CSF-deficient CD4 T cells during co-culture with BMDMs. In peritoneal macrophages, GM-CSF is sufficient to control growth, induces lipid droplet biogenesis, and requires HIF-1α expression for control. While HIF-1α-mediated control following IFN-γ stimulation requires nitric oxide, we find that HIF-1α activation by CD4 T cells and recombinant GM-CSF is nitric oxide-independent, implying a distinct pathway of activation. In addition to GM-CSF, CD4 T cells produce a factor that helps maintain phagosome membrane integrity during infection and blocks bacterial access to host lipids, a primary nutrient source. These results advance our understanding of CD4 T cell-mediated immunity to M. tuberculosis, clarify the role of nitric oxide as primarily immunomodulatory during M. tuberculosis infection, and reveal a novel mechanism for the activation of HIF-1α. Furthermore, we establish a previously unknown functional link between GM-CSF and HIF-1α and provide evidence that CD4 T cell-derived GM-CSF is a potent bactericidal effector.

Hearing the shape of a drum for light: isospectrality in photonics

The independent tailoring of wave quantities lays the foundation for controlling wave phenomena and designing wave devices. The concept of isospectrality, which suggests the existence of systems that provide identical spectra, has inspired a novel route to the spectrum-preserved engineering of wave–matter interactions in photonics, acoustics, and quantum mechanics. Recently, in photonics, constructing isospectral optical structures has become an emerging research topic to handle the intricate spectral responses of the systems composed of many-particles or inhomogeneous materials. The cornerstones in this field have stimulated the realization of non-Hermitian systems with real eigenspectra, one-dimensional structures exhibiting higher-dimensional physics, and novel engineering methodologies for broadband devices such as phase-matched multiplexers and multimodal lasing platforms. Here we review recent achievements based on isospectrality in photonics. We outline milestones in two different subfields of supersymmetric photonics and interdimensional isospectrality. We illustrate that isospectrality has paved the way for the independent control of wave quantities, showing great potential for the analytical and platform-transparent design of photonic systems with complex structures and materials.

Prospective, observational, single-centre cohort study with an independent control group matched for age and sex aimed at investigating the significance of cholinergic activity in patients with schizophrenia: study protocol of the CLASH-study

IntroductionAlterations in the cholinergic metabolism may cause various clinical symptoms of schizophrenia. In addition to the ‘monoamine hypothesis,’ neuroinflammation is also discussed as a cause of schizophrenia. To date, there has been no evidence of alterations in the central cholinergic transmitter balance in patients with schizophrenia under clinical conditions. By contrast, studies in critically ill patients have established the measurement of acetylcholinesterase activity as a suitable surrogate parameter of central cholinergic transmitter balance/possible pathophysiological changes. Butyrylcholinesterase activity has been established as a parameter indicating possible (neuro)inflammatory processes. Both parameters can now be measured using a point-of-care approach. Therefore, the primary objective of this study is to investigate whether acetylcholinesterase and butyrylcholinesterase activity differs in patients with various forms of schizophrenia. Secondary objectives address the possible association between acetylcholinesterase and butyrylcholinesterase activity and (1) schizophrenic symptoms using the Positive and Negative Syndrome Scale, (2) the quantity of antipsychotics taken and (3) the duration of illness.Methods and analysisThe study is designed as a prospective, observational cohort study with one independent control group. It is being carried out at the Department of Psychiatry and Psychotherapy III, Ulm University Hospital, Germany. Patient enrolment started in October 2020, and the anticipated end of the study is in January 2022. The enrolment period was set from October 2020 to December 2021 (extension required due to SARS-CoV-2 pandemic). The sample size is calculated at 50 patients in each group. Esterase activity is measured on hospital admission (acute symptomatology) and after referral to a postacute ward over a period of three consecutive days. The matched control group will be created after reaching 50 patients with schizophrenia. This will be followed by a comprehensive statistical analysis of the data set.Ethics and disseminationThe study was registered prospectively in the German Clinical Trials Register (DRKS-ID: DRKS00023143,URL: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00023143) after approval by the ethics committee of the University of Ulm, Germany Trial Code No. 280/20.Trial registration numberDRKS00023143; Pre-results.

The five-point non-coherent model of a distributed radar object providing the independent control of angle noise probability characteristics along two orthogonal coordinate axes

The two-dimensional five-point non-coherent model replacing a distributed radar target is explored in this work. Four fixed model points are set in corners of the square but the fifth movable point lies inside of this square. Model points are supplied by normal uncorrelated random processes. The possibilities of the five-point non-coherent model of a distributed radar object for independent control of the producing angle noise parameters along two orthogonal coordinate axes are explored. The disadvantage of this model is noted - the connection of parameters values of angle noise probability density function for two coordinate axes. The expression describing this connection is specified. Expressions determining the boundaries of the allowable coordinate values of the fifth movable point of the five-point non-coherent model, within which the model provides the set parameters of the angle noise probability density function, are defined. The arrived results are validated by program simulations.