Modulation Response Research Articles

Flicker: A review of temporal light modulation stimulus, responses, and measures

Flicker has been an important lighting system consideration for over a century. More precise terms are temporal light modulation (TLM) as the stimulus, and responses to TLM as the unwanted visual, cognitive, or physiological consequences. As lighting technology evolved, different forms of TLM emerged, and so did responses to them. Today, some LED systems – encompassing the LED, driver, and control – can result in TLM causing severe unwanted effects, while other LED systems produce no unwanted effects at all. LED systems can deliver a much wider range of luminous waveforms than conventional lighting systems, some exhibiting very high modulation depths. More than any light source before, they can elicit perceptions of the phantom array. Direct flicker effects at modulation frequencies less than about 80 Hz and the stroboscopic effect at frequencies greater than 80 Hz are fairly well understood, but the phantom array effect needs more exploration and characterisation. This review focuses on the technology and research history that led to current metrics for quantifying TLM and human responses to TLM. Visually impaired individuals may exhibit alterations in their response to TLM, but such a discussion is beyond the intent of this review. Thus, the focus is on individuals with normal visual function.

Measuring cystic fibrosis drug responses in organoids derived from 2D differentiated nasal epithelia.

Cystic fibrosis is caused by genetic defects that impair the CFTR channel in airway epithelial cells. These defects may be overcome by specific CFTR modulating drugs, for which the efficacy can be predicted in a personalized manner using 3D nasal-brushing-derived airway organoids in a forskolin-induced swelling assay. Despite of this, previously described CFTR function assays in 3D airway organoids were not fully optimal, because of inefficient organoid differentiation and limited scalability. In this report, we therefore describe an alternative method of culturing nasal-brushing-derived airway organoids, which are created from an equally differentiated airway epithelial monolayer of a 2D air-liquid interface culture. In addition, we have defined organoid culture conditions, with the growth factor/cytokine combination neuregulin-1<i>β</i> and interleukin-1<i>β</i>, which enabled consistent detection of CFTR modulator responses in nasal-airway organoid cultures from subjects with cystic fibrosis.

Connector configuration effect on the dynamic characteristics of multi-modular floating structure

In this study, a wave flume experiment is implemented in order to investigate the effect of connector topology on the dynamic characteristics of a modular floating structure. Three configurations of flexible connectors were designed for the experiment tests of a three-modular floating platform under various wave conditions. The results illustrate the module responses, relative displacements of connecting points between adjacent modules, and connector loads for floating structures with different types of connectors in the parameters region of non-dimensional module length. The comparison study demonstrates that the connector type III, which can provide appropriate constraint stiffness in all three degrees of freedom, generally delivers better dynamic stability to the floating platform. The longitudinal loads for the three types of connectors remain at the same level. Additionally, the mechanism of different types of connectors on the dynamic features of system is analyzed. This work can provide a few experimental guidelines for the connector design of floating structure in engineering practice.

Frequency-Tunable and Magnitude-Tunable Microwave Metasurface Absorbers Enabled by Shape Memory Polymers

In this article, we demonstrate a new strategy for achieving a kind of shape-controlled tunable microwave absorbers based on shape memory polymers (SMPs). Using the heat-driven shape memory effect of SMPs, a frequency-tunable absorber and a magnitude-tunable absorber are designed. Both of the designs consist of a periodic metallic array printed on both sides of the FR4 substrate, SMPs’ substrate (VeroWhitePlus) in the middle layer, and a metallic ground at the bottom. The equivalent circuit models are introduced to analyze the operational principles of the two absorbers. Furthermore, the functionalities of the designed shape-controlled tunable absorbers are investigated by full-wave simulations. For the frequency-tunable absorber design, the simulated results indicate that the resonant frequency can be tuned from 11.3 to 13.5 GHz with a frequency shift of 2.2 GHz. For the other design, the simulated results show that the reflection coefficient can be tuned from −17.00 to −1.34 dB. The proposed frequency shift responses and magnitude modulation responses are experimentally demonstrated by fabricating two prototypes containing 33 <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\times33$ </tex-math></inline-formula> units. The above designs overcome the limitation of the traditional electrically adjustable wave absorber requiring an external power supply, providing a new paradigm for the design of tunable devices.

Relative frequency response measurement of Mach-Zehnder modulators utilizing dual-carrier modulation and low-frequency detection.

A self-calibrated approach is proposed to measure the relative frequency response of Mach-Zehnder modulators (MZMs) based on dual-carrier modulation and low-frequency detection. In this scheme, a dual-carrier is generated by combining a continuous-wave light from a distributed feedback laser diode with its frequency-shifted replica. Through modulating the dual-carrier by a frequency-scanned single-tone microwave signal via the MZM under test biased at its minimum transmission point, a fixed low-frequency heterodyne signal carrying the electro-optic modulation response information is generated after photodetection, from which the relative frequency response of the MZM can be obtained. In the experiment, the relative frequency response of a commercial MZM is measured by using the proposed method, where the result fits in with those obtained by using the conventional optical spectrum analysis method and the microwave network analysis method. The proposed method features self-calibration, high frequency resolution, low-frequency detection, and usage of only a single frequency-scanned microwave source, which is favorable for characterizing the microwave performance of MZMs in backbone optical communication and microwave photonic systems.

A functional neuroimaging association study on the interplay between two schizophrenia genome-wide associated genes (CACNA1C and ZNF804A).

The CACNA1C and the ZNF804A genes are among the most relevant schizophrenia GWAS findings. Recent evidence shows that the interaction of these genes with the schizophrenia diagnosis modulates brain functional response to averbal fluencytask. To better understand how these genes might influence the risk for schizophrenia, we aimed to study the interplay between CACNA1C and ZNF804A on working memorybrain functional correlates. The analyses included functional and behavioural N-back taskdata (obtained from an fMRI protocol) and CACNA1C-rs1006737 and ZNF804A-rs1344706 genotypes for 78 healthy subjects and 78 patients with schizophrenia (matched for age, sex and premorbid IQ). We tested the effects of the epistasis between these genes as well as of the three-way interaction (CACNA1C×ZNAF804A×diagnosis) on working memory-associated activity (N-back: 2-back vs 1-back). We detected a significant CACNA1C×ZNAF804A interaction on working memory functional response in regions comprising the ventral caudate medially and within the left hemisphere, the superior and inferior orbitofrontal gyrus, the superior temporal pole and the ventral-anterior insula. The individuals with the GWAS-identified risk genotypes (CACNA1C-AA/AG and ZNF804A-AA) displayed a reduced working memory modulation response. This genotypic combination was also associated with opposite brain activity patterns between patients and controls. While further research will help to comprehend the neurobiological mechanisms of this interaction, our data highlight the role of the epistasis between CACNA1C and ZNF804A in the functional mechanisms underlying the pathophysiology of schizophrenia.

Both phosphorylation and phosphatase activity of PTEN are required to prevent replication fork progression during stress by inducing heterochromatin

PTEN is a tumor suppressor protein frequently altered in various cancers. PTEN-null cells have a characteristic of rapid proliferation with an unstable genome. Replication stress is one of the causes of the accumulation of genomic instability if not sensed by the cellular signaling. Though PTEN-null cells have shown to be impaired in replication progression and stalled fork recovery, the association between the catalytic function of PTEN regulated by posttranslational modulation and cellular response to replication stress has not been studied explicitly. To understand molecular mechanism, we find that PTEN-null cells display unrestrained replication fork progression with accumulation of damaged DNA after treatment with aphidicolin which can be rescued by ectopic expression of full-length PTEN, as evident from DNA fiber assay. Moreover, the C-terminal phosphorylation (Ser 380, Thr 382/383) of PTEN is essential for its chromatin association and sensing replication stress that, in response, induce cell cycle arrest. Further, we observed that PTEN induces HP1α expression and H3K9me3 foci formation in a C-terminal phosphorylation-dependent manner. However, phosphatase dead PTEN cannot sense replication stress though it can be associated with chromatin. Together, our results suggest that DNA replication perturbation by aphidicolin enables chromatin association of PTEN through C-terminal phosphorylation, induces heterochromatin formation by stabilizing and up-regulating H3K9me3 foci and augments CHK1 activation. Thereby, PTEN prevents DNA replication fork elongation and simultaneously causes G1-S phase cell cycle arrest to limit cell proliferation in stress conditions. Thus PTEN act as stress sensing protein during replication arrest to maintain genomic stability.

High-Sensitivity Fiber Fault Detection Method Using Feedback-Delay Signature of a Modulated Semiconductor Laser

We propose a high-sensitivity fiber fault detection method using the feedback-delay signature of a modulated semiconductor laser. The modulated laser is directed to a fiber fault and then receives the fault echo, which, in principle, forms an external cavity feedback laser. The fault location, i.e., the external cavity length, is measured by the feedback-delay signature appearing on the laser modulation response curve. The resonance effect between the modulation frequency and external cavity frequency significantly enhanced the laser sensitivity to feedback light and then led to highly sensitive fault detection. Numerical simulations based on laser rate equations predicted that −118.1 dB sensitivity to fault echo light can be obtained.

Gray matter microstructural alterations in manganese-exposed welders: a preliminary neuroimaging study.

Chronic occupational manganese (Mn) exposure is characterized by motor and cognitive dysfunction. This study aimed to investigate structural abnormalities in Mn-exposed welders compared to healthy controls (HCs). Thirty-five HCs and forty Mn-exposed welders underwent magnetic resonance imaging (MRI) scans in this study. Based on T1-weighted MRI, the voxel-based morphometry (VBM), structural covariance, and receiver operating characteristic (ROC) curve were applied to examine whole-brain structural changes in Mn-exposed welders. Compared to HCs, Mn-exposed welders had altered gray matter volume (GMV) mainly in the medial prefrontal cortex, lentiform nucleus, hippocampus, and parahippocampus. ROC analysis indicated the potential highest classification power of the hippocampus/parahippocampus. Moreover, distinct structural covariance patterns in the two groups were associated with regions, mainly including the thalamus, insula, amygdala, sensorimotor area, and middle temporal gyrus. No significant relationships were found between the findings and clinical characteristics. Our findings showed Mn-exposed welders had changed GMV and structural covariance patterns in some regions, which implicated in motivative response, cognitive control, and emotional regulation. These results might provide preliminary evidence for understanding the pathophysiology of Mn overexposure. • Chronic Mn exposure might be related to abnormal brain structural neural mechanisms. • Mn-exposed welders had morphological changes in brain regions implicated in emotional modulation, cognitive control, and motor-related response. • Altered gray matter volume in the hippocampus/parahippocampus and putamen might serve as potential biomarkers for Mn overexposure.

The Effects of Whole-Body Vibration Exercise Combined With an Isocaloric High-Fructose Diet on Osteoporosis and Immunomodulation in Ovariectomized Mice.

BackgroundOsteoporosis and immune-associated disorders are highly prevalent among menopausal women, and diet control and exercise exert beneficial effects on physiological modulation in this population. A controlled diet with a low fat content and a balanced caloric intake improves menopausal health, but the health effects of excessive fructose consumption on menopausal women are yet to be confirmed. In addition, whole-body vibration (WBV), a safe passive-training method, has been shown to have multiple beneficial effects on metabolism regulation, obesity, and bone health.MethodsThe ovariectomized (OVX) C57BL/6J model was used to verify the effects of WBV combined with a high-fructose diet (HFrD) for 16 weeks on physiological modulation and immune responses. The mice were randomly allocated to sham, OVX, OVX+HFrD, and OVX+HFrD+WBV groups, which were administered with the indicated ovariectomy, dietary and WBV training treatments. We conducted growth, dietary intake, glucose homeostasis, body composition, immunity, inflammation, histopathology, and osteoporotic assessments (primary outcomes).ResultsOur results showed that the isocaloric HFrD in OVX mice negated estrogen-deficiency–associated obesity, but that risk factors such as total cholesterol, glucose intolerance, osteoporosis, and liver steatosis still contributed to the development of metabolic diseases. Immune homeostasis in the OVX mice was also negatively affected by the HFrD diet, via the comprehensive stimulation of T cell activation, causing inflammation. The WBV intervention combined with the HFrD model significantly ameliorated weight gain, glucose intolerance, total cholesterol, and inflammatory cytokines (interferon gamma [IFN-γ], interleukin [IL]-17, and IL-4) in the OVX mice, although osteoporosis and liver steatosis were not affected compared to the negative control group. These findings indicate that an isocaloric high-fructose diet alone may not result in menopausal obesity, but that some deleterious physiological impacts still exist.ConclusionThe WBV method may modulate the physiological impacts of menopause and the HFrD diet, and should be considered as an alternative exercise prescription for people with poor compliance or who are unable or unwilling to use traditional methods to improve their health. In future studies, using the WBV method as a preventive or therapeutic strategy, combined with nutritional interventions, medication, and other exercise prescriptions, may prove beneficial for maintaining health in menopausal women.

The Antibody Dependant Neurite Outgrowth Modulation Response Involvement in Spinal Cord Injury.

Spinal cord injury (SCI) represents a major medical challenge. At present, there is still no cure to treat it efficiently and enable functional recovery below the injury site. Previously, we demonstrated that inflammation determines the fate of the physiopathology. To decipher the molecular mechanisms involved in this process, we performed a meta-analysis of our spatio-temporal proteomic studies in the time course of SCI. This highlighted the presence of IgG isotypes in both spinal cord explants and their secretomes. These IgGs were detected in the spinal cord even if no SCI occurred. However, during the time course following SCI, abundance of IgG1 and IgG2 subclasses (a, b, c) varied according to the spatial repartition. IgG1 was clearly mostly abundant at 12 h, and a switch to IgG2a was observed after 24 h. This IgG stayed predominant 3, 7, and 10 days after SCI. A protein related to IgM as well as a variable heavy chain were only detected 12 h after lesion. Interestingly, treatment with RhoA inhibitor influenced the abundance of the various IgG isotypes and a preferential switch to IgG2c was observed. By data reuse of rat dorsal root ganglion (DRG) neurons RNAseq datasets and RT-PCR experiments performed on cDNA from DRG sensory neurons ND7/23 and N27 dopaminergic neural cell lines, we confirmed expression of immunoglobulin heavy and light chains (constant and variable) encoding genes in neurons. We then identified CD16 and CD32b as their specific receptors in sensory neuron cell line ND7/23 and their activation regulated neurites outgrowth. These results suggest that during SCI, neuronal IgG isotypes are released to modulate neurites outgrowth. Therefore, we propose a new view of the SCI response involving an antibody dependent neurite outgrowth modulation (ADNM) which could be a precursor to the neuroinflammatory response in pathological conditions.

Fronto—Parietal Regions Predict Transient Emotional States in Emotion Modulated Response Inhibition via Low Frequency and Beta Oscillations

The current study evaluated the impact of task-relevant emotion on inhibitory control while focusing on midline cortical regions rather than brain asymmetry. Single-trial time-frequency analysis of electroencephalography recordings linked with response execution and response inhibition was done while thirty-four participants performed the emotion modulated stop-signal task. To evaluate individual differences across decision-making processes involved in inhibitory control, a hierarchical drift-diffusion model was used to fit data from Go-trials for each of the 34 participants. Response threshold in the early processing stage for happy and disgust emotions could be distinguished from the later processing stage at the mid-parietal and mid-frontal regions, respectively, by the single-trial power increments in low frequency (delta and theta) bands. Beta desynchronization in the mid-frontal region was specific for differentiating disgust from neutral emotion in the early as well as later processing stages. The findings are interpreted based on the influence of emotional stimuli on early perceptual processing originating as a bottom-up process in the mid-parietal region and later proceeding to the mid-frontal region responsible for cognitive control processing, which resulted in enhanced inhibitory performance. The results show the importance of mid-frontal and mid-parietal regions in single-trial dynamics of inhibitory control processing.

Water Uptake and Hormone Modulation Responses to Nitrogen Supply in Populus simonii under PEG-Induced Drought Stress

In the present study, the effects of nitrogen (N) supply on water uptake, drought resistance, and hormone regulation were investigated in Populus simonii seedlings grown in hydroponic solution with 5% polyethylene glycol (PEG)-induced drought stress. While acclimating to drought, the P. simonii seedlings exhibited a reduction in growth; differential expression levels of aquaporins (AQPs); activation of auxin (IAA) and abscisic acid (ABA) signaling pathways; a decrease in the net photosynthetic rate and transpiration rate; and an increase in stable nitrogen isotope composition (δ15N), total soluble substances, and intrinsic water use efficiency (WUEi), with a shift in the homeostasis of reactive oxygen species (ROS) production and scavenging. A low N supply (0.01 mM NH4NO3) or sufficient N supply (1 mM NH4NO3) exhibited distinct morphological, physiological, and transcriptional responses during acclimation to drought, primarily due to strong responses in the transcriptional regulation of genes encoding AQPs; higher soluble phenolics, total N concentrations, and ROS scavenging; and lower transpiration rates, IAA content, ABA content, and ROS accumulation with a sufficient N supply. P. simonii can differentially manage water uptake and hormone modulation in response to drought stress under deficient and sufficient N conditions. These results suggested that increased N may contribute to drought tolerance by decreasing the transpiration rate and O2− production while increasing water uptake and antioxidant enzyme activity.

Resonance and energy transfer in forced vibro-impact systems with linear compliance

We address a non-stationary dynamic of a vibro-impact oscillator with linear compliance under harmonic excitation. The analytic treatment is based on the well-known approximation of isolated resonance. To this end, an appropriate set of action–angle variables is formulated for the single degree of freedom conservative vibro-impact oscillator with linear compliance. At the next stage, the dynamics of the forced system is considered in conditions of a primary 1:1 resonance, common in most applications. The approximation of the isolated resonance reduces the dynamics to a planar resonance manifold with foliation induced by a global invariant derived for the 1:1 isolated resonance flow. This foliation allows for an appropriate description of the steady-state, modulated and transient responses, and their bifurcations. The results are verified with direct numeric simulations.

Frequency Response of Thermo-Optic Phase Modulators Based on Fluorinated Polyimide Polymer Waveguide.

Polymer waveguide phase modulators exhibit stable low-power phase modulation owing to their exceptional thermal confinement and high thermo-optic effect, and thus, have the merit of thermal isolation between channels, which is crucial for an optical phased array (OPA) beam scanner device. In this work, a waveguide phase modulator was designed and fabricated based on a high-refractive-index fluorinated polyimide. The propagation loss of the polyimide waveguide and the temporal response of the phase modulator were characterized. Moreover, the transfer function of the phase modulator including multiple poles and zeros was obtained from the measured frequency response. The polyimide waveguide modulator device demonstrated a fast response time of 117 μs for 1 kHz input signal, however, for 1 mHz step-function input, it exhibited an additional 5% phase change in 5 s.

Phase response measurement of spatial light modulators based on a Shack-Hartmann wavefront sensor.

It is known that the phase response of spatial light modulators (SLMs) measured by double-beam interferometers is sensitive to mechanical and environmental disturbances. This paper proposes a Shack-Hartmann wavefront sensor (SHWS) method to measure the phase response characteristics of the SLM. The results show that the phase modulation depth measured by the proposed method is 1.7581λ, and 1.7993λ by the Twyman-Green interferometer method. The difference in the phase modulation depth between the two methods is only 0.0412λ, and its relative error rate is 2.29%. It proves that the phase modulation accuracy obtained by the SHWS with lenslets of 73*73 used in this paper is equivalent to that of the Twyman-Green interferometer. Compared with the interferometer method, the SHWS method is simple, compact, and robust, has good real-time performance, and is relatively vibration insensitive. In the future, the SHWS method will play a more important role in the detection of the SLM's phase response.

The effect of the probiotic consortia on SARS-CoV-2 infection in ferrets and on human immune cell response in vitro

SummaryProbiotics have been suggested as one solution to counter detrimental health effects by SARS-CoV-2; however, data so far is scarce. We tested the effect of two probiotic consortia, OL-1 and OL-2, against SARS-CoV-2 in ferrets and assessed their effect on cytokine production and transcriptome in a human monocyte-derived macrophage (Mf) and dendritic cell (DC) model. The results showed that the consortia significantly reduced the viral load, modulated immune response, and regulated viral receptor expression in ferrets compared to placebo. In the human Mf and DC model, OL-1 and OL-2-induced cytokine production and genes related to SARS-CoV-2 antiviral immunity. The study results indicate that probiotic stimulation of the ferret immune system leads to improved antiviral immunity against SARS-COV-2, and the genes and cytokines associated with anti-SARS-CoV-2 immunity are stimulated in human immune cells in vitro. The effect of the consortia against SARS-CoV-2 warrants further investigations in human clinical trials.

PPARα Signaling: A Candidate Target in Psychiatric Disorder Management.

Peroxisome proliferator-activator receptors (PPARs) regulate lipid and glucose metabolism, control inflammatory processes, and modulate several brain functions. Three PPAR isoforms have been identified, PPARα, PPARβ/δ, and PPARγ, which are expressed in different tissues and cell types. Hereinafter, we focus on PPARα involvement in the pathophysiology of neuropsychiatric and neurodegenerative disorders, which is underscored by PPARα localization in neuronal circuits involved in emotion modulation and stress response, and its role in neurodevelopment and neuroinflammation. A multiplicity of downstream pathways modulated by PPARα activation, including glutamatergic neurotransmission, upregulation of brain-derived neurotrophic factor, and neurosteroidogenic effects, encompass mechanisms underlying behavioral regulation. Modulation of dopamine neuronal firing in the ventral tegmental area likely contributes to PPARα effects in depression, anhedonia, and autism spectrum disorder (ASD). Based on robust preclinical evidence and the initial results of clinical studies, future clinical trials should assess the efficacy of PPARα agonists in the treatment of mood and neurodevelopmental disorders, such as depression, schizophrenia, and ASD.

Local bispectral characteristics of nonlinear vibro-acoustic modulations for structural damage detection

Higher order spectral analysis is used for structural damage detection based on nonlinear vibro-acoustic modulations. A combined low-frequency vibration and high-frequency ultrasonic excitation is used, leading to nonlinear vibro-acoustic modulated responses in the presence of structural damage. The response data are analysed using a modulation signal bispectrum and bicoherence. The analysis of local amplitude and phase of these characteristics is proposed for structural damage detection. The method is illustrated using numerical simulations and experimental data. The latter involves impact damage detection in composite plates. The results show that – in contrast to the classical higher order spectral analysis – the method identifies all nonlinear damage-related coupled components correctly, distinguishes these components from undesired non-damage related modulations, and therefore shows a potential for reliable structural damage detection.

Radiosensitivity of Breast Cancer Cells Is Dependent on the Organ Microenvironment.

BackgroundDistant metastasis is the leading risk factor of death in breast cancer patients, with lung and liver being commonly involved sites of distant seeding. Ongoing clinical trials are studying the benefit from additional local treatment to these metastatic sites with radiation therapy. However, little is known about the tissue-specific microenvironment and the modulating response to treatments due to limitations of traditional in vitro systems. By using biomatrix scaffolds (BMSs) to recreate the complex composition of extracellular matrices in normal organs, we chose to study the radiotherapy response with engineered breast cancer “metastases” in liver and lung organ-specific tissues.MethodsLiver and lung BMSs were prepared for tissue culture. Human breast cancer cell lines were passaged on normal tissue culture plates or tissue culture plates coated with Matrigel, liver BMSs, and lung BMSs. Clonogenic assays were performed to measure cell survival with varying doses of radiation. Reactive Oxygen Species (ROS) detection assay was used to measure ROS levels after 6 Gy irradiation to cancer cells.ResultsThe response of breast cell lines to varying doses of radiotherapy is affected by their in vitro acellular microenvironment. Breast cancer cells grown in liver BMSs were more radiosensitive than when grown in lung BMSs. ROS levels for breast cancer cells cultured in lung and liver BMSs were higher than that in plastic or in Matrigel plate cells, before and after radiotherapy, highlighting the interaction with surrounding tissue-specific growth factors and cytokines. ROSs in both lung and liver BMSs were significantly increased after radiotherapy delivery, suggesting these sites create prime environments for radiation-induced cell death.ConclusionsThe therapeutic response of breast cancer metastases is dependent on the organ-specific microenvironment. The interaction between tissue microenvironment in these organs may identify sensitivity of therapeutic drug targets and radiation delivery for future studies.