Self-sustaining Feedback Loop Research Articles

Suppression of deep cavity aeroacoustics at low Mach number by localized surface compliance

A unique concept of utilizing localized surface compliance is proposed to suppress deep cavity aeroacoustics at a low Mach number. The core idea is to provide local absorption of the energy of aeroacoustic processes supporting cavity flow self-sustained feedback loop responsible for tonal noise generation. The concept is studied with a flow past cavity of length-to-depth ratio of 0.4 at freestream Mach number 0.09 and Reynolds number based on cavity length 4 × 104 using high-fidelity, two-dimensional direct aeroacoustic simulation. Having confirmed the replication of key aeroacoustic processes in the numerical solution through careful validation, localized surface compliance in the form of an elastic panel is strategically introduced to modify every process for cavity noise suppression. The panel natural frequency is set equal to the feedback loop characteristic frequency to facilitate its flow-induced structural resonance for energy absorption. Suppression of cavity noise pressure and power levels by 3.8 and 4.8 dB, respectively, is successfully achieved, together with an unforeseen cavity drag reduction by almost 19%. Comprehensive wavenumber–frequency analyses of the coupled aeroacoustics and flow-induced panel vibration are conducted to uncover the physical mechanism of noise suppression. The results show that the same type of aeroacoustic feedback loop occurs, but its efficacy is significantly reduced due to the exhaustion of aeroacoustic process energy to the flow-induced vibrating panel. The proposed concept is confirmed to be feasible in terms of giving remarkable cavity noise and drag suppression, yet it retains the basic problem geometry intact, which are considered important in many practical applications.

Leading edge erosion detection for a wind turbine blade using far-field aerodynamic noise

In this paper, the feasibility of using far-field acoustic measurements as a non-contact monitoring technique for wind turbine blade leading edge erosion is assessed. For this purpose, a DU96 W180 airfoil with several eroded leading edge configurations of different severities is experimentally investigated. The eroded leading edges are designed with pits, gouges and coating delamination scaled from a real eroded blade. To assess the feasibility of the technique in quasi-realistic configurations, experiments are carried out under clean and turbulent inflow conditions. Acoustic measurements are performed with a phased microphone array. In the absence of inflow turbulence, because of the low Reynolds number at which the experiments are carried out, the case with minor erosion severity shows similar far-field noise spectra as the clean leading-edge cases, i.e., the presence of tonal peaks caused by laminar boundary layer instability noise through a self-sustained feedback loop but with higher tonal amplitudes. Increasing the damage level (considered as moderate erosion), the spectra of the noise scattered from the suction side show that the tonal peaks shift to higher frequencies and have lower amplitudes, thus suggesting that the damage alters the flow features responsible for the acoustic feedback loop; whereas, the spectra from the pressure side show a broadband noise distribution. For heavy erosion, the far-field noise spectra show broadband features from both airfoil sides, thus suggesting that the damage has fully forced the transition to turbulent flow; in which case, an increase in the low-frequency content is observed. Conversely, in the presence of turbulent inflow, when comparing the noise scattered at the trailing edge, no difference is found. However, leading edge impingement noise decreases at medium–high frequency compared with the baseline case at a chord-length-based Strouhal number StC∼10. The experimental results also suggest that the delamination feature is the one which is the most easily detectable and the approach is valid for a wide range of angles of attack and inflow velocity.

The IL-1β, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19

SummaryPost-acute sequelae of COVID-19 (PASC) is emerging as global problem with unknown molecular drivers. Using a digital epidemiology approach, we recruited 8,077 individuals to the cohort study for digital health research in Germany (DigiHero) to respond to a basic questionnaire followed by a PASC-focused survey and blood sampling. We report the first 318 participants, the majority thereof after mild infections. Of those, 67.8% report PASC, predominantly consisting of fatigue, dyspnea, and concentration deficit, which persists in 60% over the mean 8-month follow-up period and resolves independently of post-infection vaccination. PASC is not associated with autoantibodies, but with elevated IL-1β, IL-6, and TNF plasma levels, which we confirm in a validation cohort with 333 additional participants and a longer time from infection of 10 months. Blood profiling and single-cell data from early infection suggest the induction of these cytokines in COVID-19 lung pro-inflammatory macrophages creating a self-sustaining feedback loop.

Study on memory characteristics of fin-shaped feedback field effect transistor

The nonvolatile and volatile memory characteristics of feedback field-effect transistors (FBFETs) with nitride charge storage layers were theoretically studied. Because of the electrons and holes stored in the nitride layer, the threshold voltage (V TH) window of 0.6 V was opened/observed. And, with the help of the formation of a positive feedback loop in the p+–n+–p–n+ doped silicon region in FBFET, it turned out that the read delay time of the FBFET for nonvolatile memory applications can be shorter than 1 ns. On the other hand, for the volatile memory applications, the FBFET can implement (a) non-destructive read operations owing to the self-sustaining feedback loop characteristic, and (b) a significantly long retention time which can suppress the power dissipation in refresh. Furthermore, the operation scheme of volatile memory mode can be simplified by setting gate voltage conditions for the hold and read operations to be identical to each other. The FBFET showed its on-state drive current of 6 × 10−5 A μm−1 and the on-/off-current ratio of 109. The potential of merging nonvolatile and volatile memory devices in a single cell is discussed and demonstrated in this work.

We need to rethink lower-division physics teaching

We need to rethink lower-division physics teaching

Motor coordination and synaptic plasticity deficits are associated with increased cerebellar activity of NADPH oxidase, CAMKII, and PKC at preplaque stage in the TgCRND8 mouse model of Alzheimer's disease.

Numerous studies indicate that the cerebellum undergoes structural and functional neurodegenerative changes in Alzheimer's disease. The purpose of this study was to examine the extent of cerebellar alterations at early, preplaque stage of the pathology in TgCRND8 mice through behavioral, electrophysiological, and molecular analysis. Balance beam test and foot-printing analysis revealed significant motor coordination and balance deficits in 2-month-old TgCRND8 mice compared to their littermates. Patch-clamp recordings performed on cerebellar slices of transgenic mice showed synaptic plasticity deficit and loss of noradrenergic modulation at parallel fiber-Purkinje cell synapse suggesting an early dysfunction of the cerebellar circuitry due to amyloid precursor protein overexpression. Finally, western blot analysis revealed an enhanced expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits p47phox and p67phox as well as Ca2+/calmodulin-dependent protein kinase and protein kinase C alpha in the cerebellum of 2-month-old transgenic mice. Therefore, we propose the existence of self-sustaining feedback loop involving the formyl peptide receptor 2-reactive oxygen species-Ca2+/calmodulin-dependent protein kinase II-protein kinase C alpha pathway that may promote reactive oxygen species generation in the early stage of Alzheimer's disease and eventually contribute to the exacerbation of pathological phenotype.

Bone: A Fertile Soil for Cancer Metastasis.

Bone is one of the most common and most dangerous sites for metastatic growth across cancer types, and bone metastasis remains incurable. Unfortunately, the processes by which cancers preferentially metastasize to bone are still not well understood. In this review, we summarize the morphological features, physical properties, and cell signaling events that make bone a unique site for metastasis and bone remodeling. The signaling crosstalk between the tumor cells and bone cells begins a vicious cycle - a self-sustaining feedback loop between the tumor cells and the bone microenvironment composed of osteoclasts, osteoblasts, other bone marrow cells, bone matrix, and vasculature to support both tumor growth and bone destruction. Through this crosstalk, bone provides a fertile microenvironment that can harbor dormant tumor cells, sometimes for long periods, and support their growth by releasing cytokines as the bone matrix is destroyed, similar to providing nutrients for a seed to germinate in soil. However, few models exist to study the late stages of bone colonization by metastatic tumor cells. We describe some of the current methodologies used to study bone metastasis, highlighting the limitations of these methods and alternative future strategies to be used to study bone metastasis. While <i>in vivo</i> animal and patient studies may provide the gold standard for studying metastasis, <i>ex vivo</i> models can be used as an alternative to enable more controlled experiments designed to study the late stages of bone metastasis.

Interleukin 17 is a chief orchestrator of immunity.

Increased understanding of the biology of interleukin 17 (IL-17) has revealed that this cytokine is a central player in immunity at the sites most exposed to microorganisms. Although it has been strongly associated with immunopathology, IL-17 also has an important role in host defense. The regulation of IL-17 secretion seems to be shared among various cell types, each of which can concomitantly secrete additional products. IL-17 has only modest activity on its own; its impact in immunity arises from its synergistic action with other factors, its self-sustaining feedback loop and, in some cases, its role as a counterpart of interferon-γ (IFN-γ). Together these attributes provide a robust response against microorganisms, but they can equally contribute to immune pathology. Here we focus on a discussion of the role of IL-17 during infection.

TNF-α-Induced microRNAs Control Dystrophin Expression in Becker Muscular Dystrophy.

The amount and distribution of dystrophin protein in myofibers and muscle is highly variable in Becker muscular dystrophy and in exon-skipping trials for Duchenne muscular dystrophy. Here, we investigate a molecular basis for this variability. In muscle from Becker patients sharing the same exon 45-47 in-frame deletion, dystrophin levels negatively correlate with microRNAs predicted to target dystrophin. Seven microRNAs inhibit dystrophin expression in vitro, and three are validated in vivo (miR-146b/miR-374a/miR-31). microRNAs are expressed in dystrophic myofibers and increase with age and disease severity. In exon-skipping-treated mdx mice, microRNAs are significantly higher in muscles with low dystrophin rescue. TNF-α increases microRNA levels in vitro whereas NFκB inhibition blocks this in vitro and in vivo. Collectively, these data show that microRNAs contribute to variable dystrophin levels in muscular dystrophy. Our findings suggest a model where chronic inflammation in distinct microenvironments induces pathological microRNAs, initiating a self-sustaining feedback loop that exacerbates disease progression.

HIV and the gut microbiota, partners in crime: breaking the vicious cycle to unearth new therapeutic targets.

The gut microbiota plays a key role in health and immune system education and surveillance. The delicate balance between microbial growth and containment is controlled by the immune system. However, this balance is disrupted in cases of chronic viral infections such as HIV. This virus is capable of drastically altering the immune system and gastrointestinal environment leading to significant changes to the gut microbiota and mucosal permeability resulting in microbial translocation from the gut into the peripheral blood. The changes made locally in the gut have far-reaching consequences on the other organs of the body starting in the liver, where microbes and their products are normally filtered out, and extending to the blood and even brain. Microbial translocation and their downstream effects such as increased indolamine 2,3-dioxygenase (IDO) enzyme expression and activity create a self-sustaining feedback loop which enhances HIV disease progression and constitute a vicious cycle of inflammation and immune activation combining viral and bacterial factors. Understanding this self-perpetuating cycle could be a key element in developing new therapies aimed at the gut microbiota and its fallout after infection.

Studying edge geometry in transiently turbulent shear flows

AbstractIn linearly stable shear flows at moderate Reynolds number, turbulence spontaneously decays despite the existence of a codimension-one manifold, termed the edge, which separates decaying perturbations from those triggering turbulence. We statistically analyse the decay in plane Couette flow, quantify the breaking of self-sustaining feedback loops and demonstrate the existence of a whole continuum of possible decay paths. Drawing parallels with low-dimensional models and monitoring the location of the edge relative to decaying trajectories, we provide evidence that the edge of chaos does not separate state space globally. It is instead wrapped around the turbulence generating structures and not an independent dynamical structure but part of the chaotic saddle. Thereby, decaying trajectories need not cross the edge, but circumnavigate it while unwrapping from the turbulent saddle.

Differential Patterns in the Periodicity and Dynamics of Clock Gene Expression in Mouse Liver and Stomach

The rhythmic recurrence of biological processes is driven by the functioning of cellular circadian clocks, operated by a set of genes and proteins that generate self-sustaining transcriptional-translational feedback loops with a free-running period of about 24 h. In the gastrointestinal apparatus, the functioning of the biological clocks shows distinct patterns in the different organs. The aim of this study was to evaluate the time-related variation of clock gene expression in mouse liver and stomach, two components of the digestive system sharing vascular and autonomic supply, but performing completely different functions. The authors analyzed the periodicity by cosinor analysis and the dynamics of variation by computing the fractional variation to assess the rate of change in gene expression. Five-week-old male Balb/c mice were exposed to 2 wks of 12-h light/12-h dark cycles, then kept in complete darkness for 3 d as a continuation of the dark span of the last light-dark cycle. The authors evaluated the expression of Bmal1, Clock, Cry1, Cry2, Per1, Per2, Per3, Rev-erbα, Rev-erbβ, Npas2, Timeless, Dbp, Csnk1d, and Csnk1e by using real-time quantitative reverse transcriptase–polymerase chain reaction (RT-PCR) in mouse liver and stomach. A significant 24-h rhythmic component was found for 10 genes in the liver (Bmal1, Clock, Cry1, Per1, Per2, Per3, Rev-erbα, Rev-erbβ, Npas2, and Dbp), and for 9 genes in the stomach (Bmal1, Cry1, Per1, Per2, Per3, Rev-erbα, Rev-erbβ, Npas2, and Dbp). In particular, Clock showed marked rhythm differences between liver and stomach, putatively due to some compensation by Npas2. The acrophase of the original values of Bmal1, Per2, Per3, Rev-erbα, Rev-erbβ, Npas2, and Dbp expression was delayed in the stomach, and the average delay expressed as mean ± SD was 14.30 ± 7.94 degrees (57.20 ± 31.78 minutes). A statistically significant difference was found in the acrophases of Bmal1 (p = .015) and Npas2 (p = .011). Fractional variations provided significant circadian rhythms for nine genes in the liver (Bmal1, Per1, Per2, Per3, Rev-erbα, Rev-erbβ, Npas2, Timeless, and Dbp), and for seven genes in the stomach (Bmal1, Clock, Per2, Rev-erbα, Npas2, Dbp, and Csnk1e). The acrophase of the fractional variations of Bmal1, Per2, Per3, Rev-erbα, Rev-erbβ, and Dbp expression was delayed in the stomach, and the average delay expressed as mean ± SD was 19.10 ± 9.39 degrees (76.40 ± 37.59 minutes). A significantly greater fractional variation was found in the liver for Clock at 06:00 h (p = .034), Per1 at 02:00 h (p = .037), and Per3 at 02:00 h (p = .029), whereas the fractional variation was greater in the stomach for Clock at 10:00 h (p = .016), and for Npas2 at 02:00 h (p = .029) and at 06:00 h (p = .044). In conclusion, liver and stomach show different phasing and dynamics of clock gene expression, which are probably related to prevailing control by different driving cues, and allow them to keep going the various metabolic pathways and diverse functional processes that they manage. (Author correspondence: g.mazzoccoli@operapadrepio.it)

Molecular Characterization of the Key Switch F Provides a Basis for Understanding the Rapid Divergence of the Sex-Determining Pathway in the Housefly

The housefly, Musca domestica, is an excellent model system to study the diversification of the pathway that specifies the sexual fate. A number of different mechanisms have been described in the housefly, which reflects in part the broad diversity of sex-determining strategies used in insects. In this study we present the molecular identification and characterization of F, which acts as the master switch in the housefly pathway. We provide evidence that F corresponds to the transformer ortholog in Musca (Mdtra), which, as a result of alternative processing, expresses functional products only in individuals committed to the female fate. We demonstrate that, once activated, a self-sustaining feedback loop will maintain the female-promoting functions of Mdtra. Absence of Mdtra transcripts in eggs of Arrhenogenic (Ag) mutant females suggests that maternally deployed Mdtra activity initiates this self-sustaining loop in the zygote. When an M factor is paternally transmitted to the zygote, the establishment of the loop is prevented at an early stage before cellularization and splicing of Mdtra shifts irreversibly to the male nonproductive mode. On the basis of the analysis of two mutant alleles we can explain the different sex-determining systems in the housefly largely as deviations at the level of Mdtra regulation. This plasticity in the housefly pathway may provide a suitable framework to understand the evolution of sex-determining mechanisms in other insect species. For instance, while sex determination in a close relative, the tsetse fly Glossina morsitans, differs at the level of the instructive signal, we find that its tra ortholog, Gmtra, is regulated in a mode similar to that of Mdtra.

The miRNA‐192/194 cluster regulates the Period gene family and the circadian clock

Several biological functions in mammals are regulated in a circadian fashion. The molecular mechanisms orchestrating these circadian rhythms have been unravelled. The biological clock, with its core transcriptional unit Bmal1/CLOCK, is composed of several self-sustaining feedback loops. In this study, we describe another mechanism impinging on the core components of the circadian clock. Using a forward genetic screen, we identified the miR-192/194 cluster as a potent inhibitor of the entire Period gene family. In accordance, the exogenous expression of miR-192/194 leads to an altered circadian rhythm. Thus, our results have uncovered a new mechanism for the control of the circadian clock at the post-transcriptional level.

Assessment of Passive Flow Control for TransonicCavity Flow Using Detached-Eddy Simulation

The implementation of internal store carriage on stealthy military aircraft has accelerated research into transonic cavity flows. Depending on the freestream Mach number and the cavity dimensions, flows inside cavities can become unsteady, threatening the structural integrity of the cavity and its contents (e.g., stores, avionics, etc.). Below a critical length-to-depth ratio, the shear layer formed along the cavity mouth has enough energy to span across the opening. This shear layer impacts the downstream cavity corner and the generated acoustic disturbances propagate upstream, causing further instabilities near the cavity front. Consequently, a self-sustained feedback loop is established. This extreme flow environment calls for flow control ideas aiming to pacify the cavity by breaking the feedback loop and controlling the breakdown of the shear layer. This is the objective of the present work, which aims to assess changes of the cavity geometry and their effect on the resulting flow using detached-eddy simulation. For the cases computed in this work, quantitative and qualitative agreement with experimental data has been obtained. All of the devices tested achieved similar reductions in overall sound pressure level in the rear half of the cavity; however, a slanted aft wall provided the largest noise reduction in the front half of the cavity.

Serum‐free mouse embryo cells generate a self‐sustaining feedback loop for an astrocyte marker protein and respond to cytokines and bisphenol A in accordance with the subtle difference in their differentiation state

Serum-free mouse embryo (SFME) cells, the astrocyte progenitor cells in the central nervous system, generated a self-sustaining feedback loop for glial fibrillary acidic protein (GFAP) expression after a period of cell passages. The period required was about 150 days (30 passages). SFME and high-GFAP-expressing SFME (G-SFME) cells were exposed to 10 ng/ml leukemia inhibitory factor (LIF) and 10 ng/ml bone morphogenetic protein 2 (BMP2) to induce differentiation and their responses to cytokine signals were analyzed. Although differentiation was significantly induced in both cell types, SFME cells showed more obvious responses to the cytokine signals. Various concentrations of bisphenol A (BPA) (0.1 pg/ml to 1 microg/ml) were added to determine its effects on cell differentiation. A completely serum-free culture was developed for effective differentiation of G-SFME cells with LIF and BMP2, and GFAP expression was significantly increased in the presence of 1-100 pg/ml BPA. These increases were attributed to excessive activation of signal transducer and activator of transcription 3 (STAT3) and mothers against decapentaplegic homolog 1 (Smad1) by the low-level BPA. The data obtained in the present study revealed that the sensitivity of the cells to LIF, BMP2 and BPA could change upon cell differentiation, suggesting that the cells may possibly respond differently to cytokines and endocrine disruptors depending on subtle differences in their differentiation state.

Jet Screech Noise Computation

The near-field screech-tone noise of a typical underexpanded circular jet issuing from a sonic nozzle is simulated numerically. The self-sustained feedback loop is automatically established in the simulation. The computed shock-cell structure, acoustic wave length, screech tone frequencies, and sound pressure levels in the near field are in good agreement with existing experimental results.

Emergent properties of networks of biological signaling pathways.

Many distinct signaling pathways allow the cell to receive, process, and respond to information. Often, components of different pathways interact, resulting in signaling networks. Biochemical signaling networks were constructed with experimentally obtained constants and analyzed by computational methods to understand their role in complex biological processes. These networks exhibit emergent properties such as integration of signals across multiple time scales, generation of distinct outputs depending on input strength and duration, and self-sustaining feedback loops. Feedback can result in bistable behavior with discrete steady-state activities, well-defined input thresholds for transition between states and prolonged signal output, and signal modulation in response to transient stimuli. These properties of signaling networks raise the possibility that information for "learned behavior" of biological systems may be stored within intracellular biochemical reactions that comprise signaling pathways.