Secondary Perturbations Research Articles

Conjugate gradient‐based active noise cancellation

AbstractActive noise cancellation schemes should synthesize proper secondary perturbations without relevant prior information. Their performance depends strongly on their adaptive mechanisms, which, sometimes, do not fulfill the severe requirements of practical setups. This research demonstrates for the first time that the adaptive conjugate gradient optimization method can be used for active noise cancellation tasks. Additionally, a stochastic model is devised for estimating its steady‐state solution, even when the secondary path is not correctly estimated. Such a theoretical analysis demonstrates the asymptotic unbiasedness of the proposed scheme when the secondary plant is perfectly estimated. Simulations reveal that the devised method can attain better asymptotic performance and a higher convergence rate than the traditional FX‐LMS algorithm, at the expense of an increased computational burden. Furthermore, simulations show that the method outperforms the standard ones for nonstationary inputs (such as speech signals).

Rethinking Hidradenitis Suppurativa Management: Insights into Bacterial Interactions and Treatment Evolution.

Hidradenitis suppurativa (HS), or acne inversa, is a chronic inflammatory dermatological condition characterized by painful and recurrent nodules and purulent abscesses. HS can have a devastating impact on the quality of life of patients. This condition is commonly localized to the axilla, groin, perineal, and inframammary regions, and can develop fistulas and sinus tracts over time. Its pathogenesis remains elusive and is best characterized at the moment as multi-factorial. Additionally, questions remain about the role of cutaneous dysbiosis as a primary HS trigger or as a secondary perturbation due to HS inflammation. This article features works in relation to HS and its interplay with bacterial microflora. We address current treatment approaches and their impact on HS-related bacteria, as well as areas of therapeutic innovation. In the future, disease-modifying or remittive therapy will likely combine an advanced/targeted anti-inflammatory approach with one that effectively modulates cutaneous and deep tissue dysbiosis.

Metal-Organic Framework Induced Stabilization of Proteins in Polymeric Nanoparticles.

Developing protein confinement platforms is an attractive research area that not only promotes protein delivery but also can result in artificial environment mimicking of the cellular one, impacting both the controlled release of proteins and the fundamental protein biophysics. Polymeric nanoparticles (PNPs) are attractive platforms to confine proteins due to their superior biocompatibility, low cytotoxicity, and controllable release under external stimuli. However, loading proteins into PNPs can be challenging due to the potential protein structural perturbation upon contacting the interior of PNPs. In this work, we developed a novel approach to encapsulate proteins in PNPs with the assistance of the zeolitic imidazolate framework (ZIF). Here, ZIF offers an additional protection layer to the target protein by forming the protein@ZIF composite via aqueous-phase cocrystallization. We demonstrated our platform using a model protein, lysozyme, and a widely studied PNP composed of poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PEG-PLGA). A comprehensive study via standard loading and release tests as well as various spectroscopic techniques was carried out on lysozyme loaded onto PEG-PLGA with and without ZIF protection. As compared with the direct protein encapsulation, an additional layer with ZIF prior to loading offered enhanced loading capacity, reduced leaching, especially in the initial stage, led to slower release kinetics, and reduced secondary structural perturbation. Meanwhile, the function, cytotoxicity, and cellular uptake of proteins encapsulated within the ZIF-bound systems are decent. Our results demonstrated the use of ZIF in assisting in protein encapsulation in PNPs and established the basis for developing more sophisticated protein encapsulation platforms using a combination of materials of diverse molecular architectures and disciplines. As such, we anticipate that the protein-encapsulated ZIF systems will serve as future polymer protein confinement and delivery platforms for both fundamental biophysics and biochemistry research and biomedical applications where protein delivery is needed to support therapeutics and/or nutrients.

Design and Realisation of Level Cascade Control System for Double-capacity Water Tanks

As a typical representative of process control, double-capacity water tank level control is a common automation control system used to control the level of two water tanks to achieve level stability and control, which is widely used in various fields of industrial production. In actual production, the accuracy and control effect of liquid level control directly affects the production cost of the factory, economic benefits and even the safety factor of the equipment. Therefore, in order to ensure safety and convenient operation, it is necessary to research and develop advanced level control methods and strategies. The sub-loop of serial stage control has a fast control effect, which can effectively overcome the influence of the perturbation into the sub-loop and improve the dynamic characteristics of the object, therefore, this paper adopts the serial stage control algorithm to achieve the constant value control of the liquid level of the double-capacity water tank and compare it with the conventional PID control algorithm, and the realisation results show that the serial stage control has a good ability to inhibit the secondary perturbation, and it can effectively improve the system's rapidity and accuracy.

Global instability of the interaction between an oblique shock and a laminar boundary layer

This study investigates the oblique shock-wave/boundary-layer interaction with a Mach number of 2.15 and a Reynolds number of 1×105. Both global stability analysis and direct numerical simulation are used to reveal the global instability characteristics and three-dimensional details of the incident shock flow. The results of global stability analysis indicate that stationary global instability occurs when the shock angle exceeds the critical angle 31.8°. At a shock angle equal to 33°, an additional unstable mode appears, which is oscillatory at large wavelength and gradually dominant when the wavelength decreases. As the wavelength is further reduced, the mode and its conjugation evolve into two stationary modes with different growth rates. A global instability criterion for incident shock flow is established based on the triple deck theory, which determines the instability only through free-stream conditions and shock angles. A direct numerical simulation is performed for the 32° shock angle case. It is found that secondary separation occurs during the nonlinear growth, which is absent in the two-dimensional base flow. Moreover, the separated flow undergoes a secondary perturbation growth, during which the dominant spanwise wavelength is doubled and the flow structures change significantly. The flow oscillates around a quasi-steady state in the end, indicating that a stationary unstable mode can develop unsteadiness without external disturbances.

Inhibitory effect of baicalein against glycation in HSA: an in vitro approach

Hyperglycaemia accelerates the aging process significantly. Diabetes problems can be mitigated by inhibiting glycation. To learn more about glycation and antiglycation mediated by methyl glyoxal and baicalein, we studied human serum albumin as a model protein. A Methylglyoxal (MGO) incubation period of seven days at 37 degrees Celsius induced glycation of Human Serum Albumin.s Hyperchromicity, decreased tryptophan and intrinsic fluorescence, increased AGE-specific fluorescence, and reduced mobility were all seen in glycated human serum albumin (MGO-HSA) in sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Fourier transform infrared spectroscopy (FT-IR) and then far ultraviolet dichroism were used to detect secondary and tertiary structural perturbations (CD). The Congo red assay (CR), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) all verified the presence of amyloid-like clumps. Structure (carbonyl groups on ketoamine moieties) (CO), physiological problems including diabetes mellitus, and cardiovascular disease, etc. are linked to the structural and functional changes in glycated HSA, as proven by these studies. Communicated by Ramaswamy H. Sarma

Rapid evolutionary repair by secondary perturbation of a primary disrupted transcriptional network.

The discrete steps of transcriptional rewiring have been proposed to occur neutrally to ensure steady gene expression under stabilizing selection. A conflict-free switch of a regulon between regulators may require an immediate compensatory evolution to minimize deleterious effects. Here, we perform an evolutionary repair experiment on the Lachancea kluyveri yeast sef1Δ mutant using a suppressor development strategy. Complete loss of SEF1 forces cells to initiate a compensatory process for the pleiotropic defects arising from misexpression of TCA cycle genes. Using different selective conditions, we identify two adaptive loss-of-function mutations of IRA1 and AZF1. Subsequent analyses show that Azf1 is a weak transcriptional activator regulated by the Ras1-PKA pathway. Azf1 loss-of-function triggers extensive gene expression changes responsible for compensatory, beneficial, and trade-off phenotypes. The trade-offs can be alleviated by higher cell density. Our results not only indicate that secondary transcriptional perturbation provides rapid and adaptive mechanisms potentially stabilizing the initial stage of transcriptional rewiring but also suggest how genetic polymorphisms of pleiotropic mutations could be maintained in the population.

Cascade PID Control Systems Based on DNA Strand Displacement With Application in Polarization of Tumor-Associated Macrophages

Disturbances are widespread in biochemical systems. Nowadays, prevalent single-loop control strategies only take external disturbances into account. However, internal perturbations that threaten the stability of biochemical systems are invariably ignored. In this paper, a DNA strand displacement (DSD)-based cascade PID control system is designed. In addition to traditionally realizing the tracking of reference input and the attenuation of primary disturbance, the presented control approach also innovatively completes the rejection of secondary disturbance. Specifically, the dynamics of the reference input signal are first governed by a first-order low-pass filter integrated with cascade PID control systems, which efficiently avoids the excessive response of the cascaded primary and secondary controllers to the reference signal. Then, cascade PID controllers and second-order time-delay plants are constructed by utilizing the chemical reaction network (CRN) and the DSD. In terms of secondary perturbation suppression, the obtained control scheme significantly outperforms the single-loop PID control scheme with a smaller overshoot and faster settling time. Finally, the DSD-based cascade PID control method is applied to regulate gene expressions of interferon regulatory factor 4 (IRF4) and interferon regulatory factor 5 (IRF5) that affect the polarization of tumor-associated macrophages (TAMs). Compared with the single-loop PID control strategy, the control strategy exhibits a better inhibitory effect on IRF5 gene overexpression (internal disturbance) and TAMs endogenous gene expression (external disturbance).

Decay times of atmospheric acoustic–gravity waves after deactivation of wave forcing

Abstract. High-resolution numerical simulations of non-stationary, nonlinear acoustic–gravity waves (AGWs) propagating upwards from surface wave sources are performed for different temporal intervals relative to activation and deactivation times of the wave forcing. After activating surface wave sources, amplitudes of AGW spectral components reach a quasi-stationary state. Then the surface wave forcing is deactivated in the numerical model, and amplitudes of vertically traveling AGW modes quickly decrease at all altitudes due to discontinuations of the upward propagation of wave energy from the wave sources. However, later the standard deviation of residual and secondary wave perturbations experiences a slower quasi-exponential decrease. High-resolution simulations allowed, for the first time, for the estimation of the decay times of this wave noise produced by slow residual, quasi-standing and secondary AGW spectral components, which vary between 20 and 100 h depending on altitude and the rate of wave source activation and deactivation. The standard deviations of the wave noise are larger for the case of sharp activation and deactivation of the wave forcing compared to the steep processes. These results show that transient wave sources may create long-lived wave perturbations, which can form a background level of wave noise in the atmosphere. This should be taken into account in parameterizations of atmospheric AGW impacts.

Effect of crocin on glycated human low-density lipoprotein: A protective and mechanistic approach

Human low-density lipoprotein (LDL) is known to have a role in coronary artery diseases when it undergoes modification due to hyperglycaemic conditions. Plant products like crocin play an essential role in protecting against oxidative stress and in the production of advanced glycation end-products (A.G.E.s). In this study, the anti-glycating effect of crocin was analyzed using various biochemical, spectroscopic, and in silico approaches. Glycation-mediated oxidative stress was confirmed by nitroblue tetrazolium, carbonyl content, and lipid peroxidation assays, and it was efficiently protected by crocin in a concentration-dependent manner. A.N.S. fluorescence, thioflavin T (ThT) assay, and electron microscopy confirmed that the structural changes in LDL during glycation lead to the formation of fibrillar aggregates, which can be minimized by crocin treatment. Moreover, secondary structural perturbations in LDL were observed using circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR), where crocin was found to prevent the loss of secondary structure in glycated LDL. Spectroscopic studies like U.V. absorbance, fluorescence spectroscopy, CD, FTIR, and fluorescence resonance energy transfer (FRET) provided insights into the interaction mechanism between LDL and crocin. Molecular docking supports these results with a highly negative binding energy of −10.3 kcal/mol, suggesting the formation of a stable ldl-crocin complex. Our study indicates that crocin may be a potent protective agent against coronary artery diseases by limiting the glycation of LDL in people with such disorders.

Generalized multistability and its control in a laser.

We revisit the laser model with cavity loss modulation, from which evidence of chaos and generalized multistability was discovered in 1982. Multistability refers to the coexistence of two or more attractors in nonlinear dynamical systems. Despite its relative simplicity, the adopted model shows us how the multistability depends on the dissipation of the system. The model is then tested under the action of a secondary sinusoidal perturbation, which can remove bistability when a suitable relative phase is chosen. The surviving attractor is the one with less dissipation. This control strategy is particularly useful when one of the competing attractors is a chaotic attractor.

Active Flow Control of Supersonic Jet Using Streamwise Pulsed Blowing

The present study investigates a novel control strategy to create a sweeping oscillatory jet using fluidic actuation principle. A supersonic underexpanded primary jet issued into a suddenly expanding duct is oscillated by giving cyclic pulsed secondary jet blowing in the top and bottom step regions of the suddenly expanding duct. The current study employs the bistable nature of jet expansion seen in a suddenly expanding duct for the jet oscillation. The cyclic perturbations (pulsed secondary jet blowing) given in the streamwise direction switch the direction of the asymmetric jet expansion of the underexpanded primary supersonic jet to the top and bottom wall alternatively, thereby creating an oscillatory supersonic jet. It is found that the switching of the direction of the primary jet to any one wall is caused by the Coanda effect produced by the secondary jet issued in the corresponding wall side. The results show that the primary jet quickly responds to the secondary jet perturbations and that the supersonic primary jet oscillation frequency nearly matches secondary jet perturbation frequency. A parametric study to investigate the jet oscillation characteristics with various secondary jet oscillation frequencies and mass flow rate ratios are also being carried out in the present study. It is found that the jet oscillation frequency increases with increase in the secondary jet pulsation frequency. The jet deflection is found to increase with increase in the secondary jet to primary jet mass flow ratio (blowing ratio) up to a critical limit, after which the increment in jet deflection ceases due to the restrictions imposed by the duct geometry.

Elucidating the binding and inhibitory potential of p-coumaric acid against amyloid fibrillation and their cytotoxicity: Biophysical and docking analysis

P-Coumaric acid (p-CA) is a plant metabolite with anti-inflammatory and antioxidant effects. Due to its therapeutic potential, p-CA has attracted much attention from the scientific community lately. Oxidative stress, amyloid formation, and impaired proteasomal degradation are hallmarks of neurodegenerative diseases like Alzheimer's (AD) and are targets for developing therapeutics against such conditions. Here, we have investigated the anti-amyloidogenic properties of p-coumaric acid on hen egg white lysozyme (HEWL). Heat, pH, and agitation (55 °C, pH 2.0, 600 rpm) stress were used to induce amyloid formation in lysozyme. The aggregates characterization was done by turbidity, Rayleigh light scattering (RLS), and thioflavin-T (ThT) assays. Moreover, ANS (1-anilino naphthalene sulphate) binding assay and circular dichroism (CD) were employed to unveil protein hydrophobicity and secondary structure perturbation, respectively. Lysozyme demonstrated increased hydrophobicity and transition of α-helix to β-sheet under aggregating conditions. Moreover, co-incubation of lysozyme with p-coumaric acid attenuates the process of amyloid in a concentration dependent manner. At 50 and 200 μM concentrations of p-coumaric acid, lysozyme retained its native-like folded structure. Cytotoxicity protection on human SK-N-SH neuroblastoma cell line was also observed using MTT assay and phase contrast microscopy. In addition, transmission electron microscopy (TEM) reaffirms the fibrillar nature of lysozyme aggregates and their attenuation by p-coumaric acid. The steady state fluorescence revealed that the mode of fluorescence quenching for the HEWL-p-coumaric acid interaction is static rather than dynamic. Moderate strength of binding in order of 104 M−1 exists between HEWL and p-coumaric acid. Thermodynamic parameters (∆H and ∆S) obtained from van't Hoff plot suggested spontaneous reaction with hydrophobic interaction. A slight micro-environmental change in HEWL around Tyr residue was observed during the binding process with the help of synchronous fluorescence. Molecular docking analysis reported the involvement of amino acid residues (TRP63, LEU75, ASP101, LYS97) to form a complex between HEWL-p-coumaric acid. The observed anti-amyloidogenic and inherent antioxidative properties of p-coumaric acid could be helpful to design a neuroprotective agent.

Individual Wave Propagations in Ionosphere and Troposphere Triggered by the Hunga Tonga-Hunga Ha’apai Underwater Volcano Eruption on 15 January 2022

The devastating Hunga Tonga-Hunga Ha’apai underwater volcano erupted at ~04:15 UT on 15 January 2022. We captured the waves that erupted from the volcano propagating in the ionosphere by monitoring total electron content (TEC) perturbations utilizing ground-based global navigation satellite system (GNSS) receivers that receive electromagnetic signals transmitted from the geostationary satellites operated by the BeiDou Navigation Satellite System (BDS). Meanwhile, ground barometers detected unusual enhancements of air pressure traveling in the troposphere. A novel phenomenon shows that the waves can individually propagate with a speed of ~335 m/s in the ionosphere, which is faster than its’ ~305 m/s in the troposphere. We further examined multiple geophysical data at the particular site of the novel instrumental array. Analytical results show that the pressure enhancements traveling in the troposphere not only downward trigger ground vibrations mainly in the horizontal components without obvious time difference, but also upward, leading the secondary TEC perturbations with a ~12-min delay.

Pathophysiology and risk factors of peripartum cardiomyopathy.

Peripartum cardiomyopathy (PPCM) is a potentially fatal form of idiopathic heart failure with variable prevalence across different countries and ethnic groups. The cause of PPCM is unclear, but environmental and genetic factors and pregnancy-associated conditions such as pre-eclampsia can contribute to the development of PPCM. Furthermore, animal studies have shown that impaired vascular and metabolic function might be central to the development of PPCM. A better understanding of the pathogenic mechanisms involved in the development of PPCM is necessary to establish new therapies that can improve the outcomes of patients with PPCM. Pregnancy hormones tightly regulate a plethora of maternal adaptive responses, including haemodynamic, structural and metabolic changes in the cardiovascular system. In patients with PPCM, the peripartum period is associated with profound and rapid hormonal fluctuations that result in a brief period of disrupted cardiovascular (metabolic) homeostasis prone to secondary perturbations. In this Review, we discuss the latest studies on the potential pathophysiological mechanisms of and risk factors for PPCM, with a focus on maternal cardiovascular changes associated with pregnancy. We provide an updated framework to further our understanding of PPCM pathogenesis, which might lead to an improvement in disease definition.

Glycogen Storage Disease Type Ia: Current Management Options, Burden and Unmet Needs.

Glycogen storage disease type Ia (GSDIa) is caused by defective glucose-6-phosphatase, a key enzyme in carbohydrate metabolism. Affected individuals cannot release glucose during fasting and accumulate excess glycogen and fat in the liver and kidney, putting them at risk of severe hypoglycaemia and secondary metabolic perturbations. Good glycaemic/metabolic control through strict dietary treatment and regular doses of uncooked cornstarch (UCCS) is essential for preventing hypoglycaemia and long-term complications. Dietary treatment has improved the prognosis for patients with GSDIa; however, the disease itself, its management and monitoring have significant physical, psychological and psychosocial burden on individuals and parents/caregivers. Hypoglycaemia risk persists if a single dose of UCCS is delayed/missed or in cases of gastrointestinal intolerance. UCCS therapy is imprecise, does not treat the cause of disease, may trigger secondary metabolic manifestations and may not prevent long-term complications. We review the importance of and challenges associated with achieving good glycaemic/metabolic control in individuals with GSDIa and how this should be balanced with age-specific psychosocial development towards independence, management of anxiety and preservation of quality of life (QoL). The unmet need for treatment strategies that address the cause of disease, restore glucose homeostasis, reduce the risk of hypoglycaemia/secondary metabolic perturbations and improve QoL is also discussed.

Poly(ADP-ribose) polymerase 1 regulates mitochondrial DNA repair in an NAD-dependent manner

Mitochondrial DNA is located in organelle that house essential metabolic reactions and contains high reactive oxygen species. Therefore, mitochondrial DNA suffers more oxidative damage than its nuclear counterpart. Formation of a repair enzyme complex is beneficial to DNA repair. Recent studies have shown that mitochondrial DNA polymerase (Pol γ) and poly(ADP-ribose) polymerase 1 (PARP1) were found in the same complex along with other mitochondrial DNA repair enzymes, and mitochondrial PARP1 level is correlated with mtDNA integrity. However, the molecular basis for the functional connection between Pol γ and PARP1 has not yet been elucidated because cellular functions of PARP1 in DNA repair are intertwined with metabolism via NAD+ (nicotinamide adenosine dinucleotide), the substrate of PARP1, and a metabolic cofactor. To dissect the direct effect of PARP1 on mtDNA from the secondary perturbation of metabolism, we report here biochemical studies that recapitulated Pol γ PARylation observed in cells and showed that PARP1 regulates Pol γ activity during DNA repair in a metabolic cofactor NAD+ (nicotinamide adenosine dinucleotide)-dependent manner. In the absence of NAD+, PARP1 completely inhibits Pol γ, while increasing NAD+ levels to a physiological concentration that enables Pol γ to resume maximum repair activity. Because cellular NAD+ levels are linked to metabolism and to ATP production via oxidative phosphorylation, our results suggest that mtDNA damage repair is coupled to cellular metabolic state and the integrity of the respiratory chain.

Bias‐compensated FX‐LMS algorithm

Active noise control is an expanding field that requires a suitable synthesis of secondary perturbations. Unfortunately, most schemes for noise cancelling do not take into account that the input signal that drives the adaptive filter can be noisy. In this Letter, it is theoretically shown that noise perturbations in the excitation data degrade the performance of the standard filtered-x least mean squares (FX-LMS) algorithm. Furthermore, a method that compensates such an issue is devised, and a first-order stochastic analysis of the resulting algorithm is performed. The results reveal that the proposed scheme outperforms the standard FX-LMS algorithm, even when the variance of the additive noise in the input is not accurately estimated.

Inertia–Gravity Waves Breaking in the Middle Atmosphere at High Latitudes: Energy Transfer and Dissipation Tensor Anisotropy

Abstract We present direct numerical simulations of inertia–gravity waves breaking in the middle–upper mesosphere. We consider two different altitudes, which correspond to the Reynolds number of 28 647 and 114 591 based on wavelength and buoyancy period. While the former was studied by Remmler et al., it is here repeated at a higher resolution and serves as a baseline for comparison with the high-Reynolds-number case. The simulations are designed based on the study of Fruman et al., and are initialized by superimposing primary and secondary perturbations to the convectively unstable base wave. Transient growth leads to an almost instantaneous wave breaking and secondary bursts of turbulence. We show that this process is characterized by the formation of fine flow structures that are predominantly located in the vicinity of the wave’s least stable point. During the wave breakdown, the energy dissipation rate tends to be an isotropic tensor, whereas it is strongly anisotropic in between the breaking events. We find that the vertical kinetic energy spectra exhibit a clear 5/3 scaling law at instants of intense energy dissipation rate and a cubic power law at calmer periods. The term-by-term energy budget reveals that the pressure term is the most important contributor to the global energy budget, as it couples the vertical and the horizontal kinetic energy. During the breaking events, the local energy transfer is predominantly from the mean to the fluctuating field and the kinetic energy production is in balance with the pseudo kinetic energy dissipation rate.

Small Scale Non-Invasive Imaging Using Magnetic Induction Tomography - Hardware Desig

This study is conducted to preliminary image the conductivity profile through the development of small scale non-invasive Magnetic Induction Tomography (MIT) system. It is proved that the Magnetic Induction Tomography interested in mapping the passive electrical properties of materials; conductivity (σ), permittivity (e) and permeability (µ) in both process and medical tomography. The system is realized by designing the functional ferrite-core coil sensors, electronic measurements circuits for excitation and receiving coil, data acquisition system for transferring the data to the PC and suitable image reconstruction algorithm for providing the conductivity distributions measurement. The important characteristic for excitation coil is the one that can maintain the stability the optimum sine wave frequency ranging from 400 kHz up to 10 MHz. The sine waves are fed to the excitation coil through the application of high current amplifier component respectively. In the experiments, the copper phantom represent as high conductivity material were placed into the region of interest. The initial 16 channel MIT consists of 8 excitation coil and 8 receiving coil stacked alternately. On the receiving circuit, the major problem is the weak secondary signal perturbation sensed by the receiving coil has been improved by placing the variable amplifier on each receiver. The enhancement of conductivity profile imaging has been made by using a common Linear Back Projection (LBP) algorithm. The measurement was done on single and dual arrangement of copper phantom aligns in random coordinate so that the sensitivity of the excitation and receiving coil sensor can be experimentally observed. The imaging’s results show that the hardware’s and algorithm used was capable to process the data captured at the receiver. The results obtained can be useful for further improvement and research towards magnetic induction tomography.