Overcoming the Tumor Collagen Barriers: A Multistage Drug Delivery Strategy for DDR1-Mediated Resistant Colorectal Cancer Therapy.

The extracellular matrix (ECM) is critical for drug resistance in colorectal cancer (CRC). The abundant collagen within the ECM significantly influences tumor progression and matrix-mediated drug resistance (MMDR) by binding to discoidin domain receptor 1 (DDR1), but the specific mechanisms by which tumor cells modulate ECM via DDR1 and ultimately regulate TME remain poorly understand. Furthermore, overcoming drug resistance by modulating the tumor ECM remains a challenge in CRC treatment. In this study, a novel mechanism is elucidated by which DDR1 mediates the interactions between tumor cells and collagen, enhances collagen barriers, inhibits immune infiltration, promotes drug efflux, and leads to MMDR in CRC. To address this issue, a multistage drug delivery system carrying DDR1-siRNA and chemotherapeutic agents is employed to disrupt collagen barriers by silencing DDR1 in tumor, enhancing chemotherapy drugs diffusion and facilitating immune infiltration. These findings not only revealed a novel role for collagen-rich matrix mediated by DDR1 in tumor resistance, but also introduced a promising CRC treatment strategy.

Flexoelectricity Modulated Electron Transport of 2D Indium Oxide.

The phenomenon of flexoelectricity, wherein mechanical deformation induces alterations in the electron configuration of metal oxides, has emerged as a promising avenue for regulating electron transport. Leveraging this mechanism, stress sensing can be optimized through precise modulation of electron transport. In this study, the electron transport in 2D ultra-smooth In2O3 crystals is modulated via flexoelectricity. By subjecting cubic In2O3 (c-In2O3) crystals to significant strain gradients using an atomic force microscope (AFM) tip, the crystal symmetry is broken, resulting in the separation of positive and negative charge centers. Upon applying nano-scale stress up to 100 nN, the output voltage and power values reach their maximum, e.g. 2.2 mV and 0.2 pW, respectively. The flexoelectric coefficient and flexocoupling coefficient of c-In2O3 are determined as ≈0.49 nC m-1 and 0.4 V, respectively. More importantly, the sensitivity of the nano-stress sensor upon c-In2O3 flexoelectric effect reaches 20 nN, which is four to six orders smaller than that fabricated with other low dimensional materials based on the piezoresistive, capacitive, and piezoelectric effect. Such a deformation-induced polarization modulates the band structure of c-In2O3, significantly reducing the Schottky barrier height (SBH), thereby regulating its electron transport. This finding highlights the potential of flexoelectricity in enabling high-performance nano-stress sensing through precise control of electron transport.

Tailoring Catalysis of Encapsulated Pt Nanoparticles by Pore Wall Engineering of Covalent Organic Frameworks.

While supported metal nanoparticles (NPs) have shown significant promise in heterogeneous catalysis, precise control over their interaction with the support, which profoundly impacts their catalytic performance, remains a significant challenge. In this study, Pt NPs are incorporated into thioether-functionalized covalent organic frameworks (denoted COF-Sx), enabling precise control over the size and electronic state of Pt NPs by adjusting the thioether density dangling on the COF pore walls. Notably, the resulting Pt@COF-Sx demonstrate exceptional selectivity (>99%) in catalytic hydrogenation of p-chloronitrobenzene to p-chloroaniline, in sharp contrast to the poor selectivity of Pt NPs embedded in thioether-free COFs. Furthermore, the conversion over Pt@COF-Sx exhibits a volcano-type curve as the thioether density increases, due to the corresponding change of accessible Pt sites. This work provides an effective approach to regulating the catalysis of metal NPs via their microenvironment modulation, with the aid of rational design and precise tailoring of support structure.

Cardiac autonomic modulation and exercise capacity in older adults with intellectual disability: A 6-month randomised control trial.

BACKGROUND: Despite reported physical and functional improvements with aerobic and sprint interval training (SIT) protocols in individuals with intellectual disability (ID), it is not known if these interventions' effectivity would promote improvements in cardiac autonomic modulation. This study aimed to investigate if a 6-month SIT or a continuous aerobic programme could enhance physical performance and cardiac autonomic modulation at rest, during physical activity (PA) and after it in older adults with an ID. METHODS: This is a randomised control trial. Participants with ID (age: 50.58 ± 7.25) were allocated to one of three groups [multicomponent aerobic training group (MATG), multicomponent interval sprint training group (MISTG) and control group (CG)]. The programmes lasted 24 weeks, with three sessions/week, 75-90 min per session. The HRV was analysed at rest and recovery, the delta of heart rate (HR) was analysed during 6MWT, and the HR t-off kinetics was analysed in recovery after 6MWT. RESULTS: There were not found differences between groups, moments, or interaction for cardiac autonomic modulation at rest and recovery. During exercise, only MSITG showed a significant increase of HR between rest and the first 30 s of exercise (P < 0.05). Physical performance increased only in MSITG (P < 0.05), while CG showed a significant reduction (P < 0.01). CONCLUSIONS: The MSITG improved the physical performance and the vagal withdrawal at the beginning of the submaximal exercise. These findings suggest that high-intensity exercise may positively impact baroreflex function, mitigating the decline in autonomic reflex response capacity associated with aging in individuals with ID.

A concise review of the nutritional profiles, microbial dynamics, and health impacts of fermented mushrooms.

Mushrooms have garnered significant attention for their nutritional composition and potential health benefits, including antioxidant, antihypertensive, and cholesterol-lowering properties. This review explores the nutritional composition of edible mushrooms, including their high protein content, essential amino acids, low fat, cholesterol levels, and bioactive compounds with medicinal value. Moreover, the study analyzes the microbiology of mushroom fermentation, focusing on the diverse microbial ecosystem involved in the transformation of raw mushrooms and the preservation methods employed to extend their shelf life. Special emphasis is placed on lactic acid fermentation as a cost-effective and efficient preservation technique. It involves controlling the growth of lactic acid bacteria to enhance the microbial stability and nutritional quality of mushrooms. Furthermore, the bioactivities of fermented mushrooms are elucidated, which are antioxidant, antimicrobial, anticancer, anti-glycemic, immune modulatory, and other biological activities. The mechanisms underlying these bioactivities are explored, emphasizing the role of fermented mushrooms in suppressing free radicals, enhancing antioxidant defenses, and modulating immune responses. Overall, this review provides comprehensive insights into the nutritional composition, microbiology, bioactivities, and underlying mechanisms of fermented mushrooms, highlighting their potential as functional foods with significant health-promoting properties.

Tannic acid as a biphasic modulator of tau protein liquid-liquid phase separation.

Tannic acid (TA) is a natural polyphenol that shows great potential in the field of biomedicine due to its anti-inflammatory, anti-oxidant, anti-bacterial, anti-tumor, anti-virus, and neuroprotective activities. Recent studies have revealed that liquid-liquid phase separation (LLPS) is closely associated with protein aggregation. Therefore, modulating LLPS offers new insights into the treatment of neurodegenerative diseases. In this study, we investigated the influence of TA on the LLPS of the Alzheimer's-related protein tau and the underlying mechanism. Our findings indicate that TA affects the LLPS of tau in a biphasic manner, with initial promotion and subsequent suppression as the TA to tau molar ratio increases. TA modulates tau phase separation through a combination of hydrophobic interactions and hydrogen bonds. The balance between TA-tau and tau-tau interactions is found to be relevant to the material properties of TA-induced tau condensates. We further illustrate that the modulatory activity of TA in phase separation is highly dependent on the target proteins. These findings enhance our understanding of the forces driving tau LLPS under different conditions, and may facilitate the identification and optimization of compounds that can rationally modulate protein phase transition in the future.

Cholinergic modulation in the vertebrate auditory pathway.

Acetylcholine (ACh) is a prevalent neurotransmitter throughout the nervous system. In the brain, ACh is widely regarded as a potent neuromodulator. In neurons, ACh signals are conferred through a variety of receptors that influence a broad range of neurophysiological phenomena such as transmitter release or membrane excitability. In sensory circuitry, ACh modifies neural responses to stimuli and coordinates the activity of neurons across multiple levels of processing. These factors enable individual neurons or entire circuits to rapidly adapt to the dynamics of complex sensory stimuli, underscoring an essential role for ACh in sensory processing. In the auditory system, histological evidence shows that acetylcholine receptors (AChRs) are expressed at virtually every level of the ascending auditory pathway. Despite its apparent ubiquity in auditory circuitry, investigation of the roles of this cholinergic network has been mainly focused on the inner ear or forebrain structures, while less attention has been directed at regions between the cochlear nuclei and midbrain. In this review, we highlight what is known about cholinergic function throughout the auditory system from the ear to the cortex, but with a particular emphasis on brainstem and midbrain auditory centers. We will focus on receptor expression, mechanisms of modulation, and the functional implications of ACh for sound processing, with the broad goal of providing an overview of a newly emerging view of impactful cholinergic modulation throughout the auditory pathway.

Allogeneic B cell immunomodulatory therapy in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is an orphan neurodegenerative disease. Immune system dysregulation plays an essential role in ALS onset and progression. Our preclinical studies have shown that the administration of exogenous allogeneic B cells improves outcomes in murine models of skin and brain injury through a process termed pligodraxis, in which B cells adopt an immunoregulatory and neuroprotective phenotype in an injured environment. Here, we investigated the effects of B-cell therapy in the SOD1G93A mouse preclinical model of ALS and in a person living with ALS. Purified splenic mature naïve B cells from haploidentical donor mice were administered intravenously in SOD1G93A mice for a total of 10 weekly doses. For the clinical study in a person with advanced ALS, IgA gammopathy of unclear significance, and B lymphopenia, CD19+ B cells were positively selected from a healthy haploidentical donor and infused intravenously twice, at a 60-day interval. Repeated intravenous B-cell administration was safe and significantly delayed disease onset, extended survival, reduced cellular apoptosis, and decreased astrogliosis in SOD1G93A mice. Repeated B-cell infusion in a person with ALS was safe and did not appear to generate a clinically evident inflammatory response. An improvement of 5 points on the ALSFRS-R scale was observed after the first infusion. Levels of inflammatory markers showed persistent reduction post-infusion. This represents a first demonstration of the efficacy of haploidentical B-cell infusion in the SOD1G93A mouse and the safety and feasibility of using purified haploidentical B lymphocytes as a cell-based therapeutic strategy for a person with ALS.

Chronic sleep deficiency and its impact on pain perception in healthy females.

Acute sleep deprivation in experimental studies has been shown to induce pain hypersensitivity in females. However, the impact of natural sleep deficiency and fluctuations across the week on pain perception remains unclear. A sleep-monitoring headband and self-reports were utilized to assess objective and subjective sleep in longer (> 6 hr) and short sleepers (< 6 hr). Pain sensitivity measures including heat, cold, pressure pain thresholds, pain inhibition (conditioned pain modulation) and facilitation (tonic pain summation) were assessed on Mondays and Fridays. Forty-one healthy young (23.9 ± 0.74 years) women participated. Short sleepers slept on average 2 hr less than longer sleepers (297.9 ± 8.2 min versus 418.5 ± 10.9 min) and experienced impaired pain inhibitory response (mean = -21.14 ± 7.9°C versus mean = 15.39 ± 9.5°C; p = 0.005). However, no effect was observed in pain thresholds and pain summation (p > 0.05). Furthermore, pain modulatory responses differed between Mondays and Fridays. Chronic sleep deficiency (< 6 hr) compromises pain responses, notably on Mondays. Maintaining a consistent sleep pattern with sufficient sleep (> 6 hr) throughout the week may protect against pain sensitization and the development of chronic pain in females. Further research is needed, especially in patients with chronic pain.

Evaluation of low-dose pediatric chest CT examination using in-house developed various age-size pediatric chest phantoms.

PURPOSE: This study aims to develop Various Age-size Pediatric Chest Phantoms (VAPC) to evaluate low-dose protocol that approximates clinical conditions achieved by low organ-specific doses and optimal image quality among the challenges of pediatric size variations. METHODS: Three original pediatric data aged 1, 4, and 7 years were used as a reference for developing VAPC phantoms. Six protocols, namely standard dose (STD) and low dose (low mA and low kV) reconstructed using Filtered Back Projection (FBP) and iterative reconstruction (IR) algorithms, were investigated. This study directly measured the lungs, heart, and spinal cord dose using LD-V1 film. Linearity, Modulation Transfer Function (MTF), Contrast to Noise Ratio (CNR), and Noise Power Spectrum (NPS) were evaluated to assess the CT image quality of the VAPC phantom. RESULTS: This study found that the mean organ-specific dose was higher than CTDIvol. A Comparison of mean lung doses showed VAPC phantom 1 (y.o.) received 74.8% and 137.2% more doses than 4 (y.o.) and 7 (y.o.), respectively. Low kV produces a lower organ dose than low mA. The linearity of CT numbers is not biased at low doses. Differences in age measures significantly influenced organ-specific dose, MTF, CNR, and NPS. CONCLUSION: Smaller pediatrics are still exposed to higher doses at low-dose examinations, whereas larger pediatrics have lower contrast resolution and increased image noise. CT number linearity is unbiased. The combination of low kV with FBP produces higher spatial resolution, while low mA with IR effectively reduces noise to detect low-contrast objects better.

Regulation of anthocyanin synthesis in red lettuce in plant factory conditions: A review.

Anthocyanins, natural pigments known for their vibrant hues and beneficial properties, undergo intricate genetic control. However, red vegetables grown in plant factories frequently exhibit reduced anthocyanin synthesis compared to those in open fields due to factors like inadequate light, temperature, humidity, and nutrient availability. Comprehending these factors is essential for optimizing plant factory environments to enhance anthocyanin synthesis. This review insights the impact of physiological and genetic factors on the production of anthocyanins in red lettuce grown under controlled conditions. Further, we aim to gain a better understanding of the mechanisms involved in both synthesis and degradation of anthocyanins. Moreover, this review summarizes the identified regulators of anthocyanin synthesis in lettuce, addressing the gap in knowledge on controlling anthocyanin production in plant factories, with potential implications for various crops beyond red lettuce.

Fluctuation of fine motor skills throughout the menstrual cycle in women.

The effect of the menstrual cycle on fine motor skills is unclear. This study determined whether the menstrual cycle affected fine motor skills and related neural activities. Nineteen women with regular menstrual cycles were tested for fine motor skills using two types of tasks: grooved pegboard task (GPT), which evaluates motor control with high freedom of movements, and force modulation task (FMT), which evaluates more complex and fine motor control with low freedom of movements. We also assessed primary motor cortex intracortical circuits and sensorimotor integration using paired-pulse transcranial magnetic stimulation to reveal why the menstrual cycle affects fine motor skills. The present study indicated that fine motor skills assessed by FMT varied throughout the menstrual cycle while those measured by GPT did not. These results suggest that fine motor skills requiring more complex and fine control may be affected by the menstrual cycle. Additionally, changes in fine motor skills throughout the menstrual cycle may be associated with the severity of menstruation-related symptoms.

Modeling and virtual simulation of the boost chopper by DCM using the optimal PIDF control.

This work introduces an improved method for modeling and simulating the Boost Converter utilizing Duty Cycle Modulation (DCM) regulated by an optimum PIDF (Proportional-Integral-Derivative with Filter) regulator. We optimized the characteristic parameters of the PIDF regulator for a second-order system generated from its transfer function by using a mix of theoretical study and simulation using the Matlab/LQR tool. The conventional PID parameters in the time domain were converted into their corresponding LQR (Linear Quadratic Regulator) counterparts, allowing for the solution of the Riccati problem and the creation of an optimum state trajectory model. The results of analog virtual simulations done in a Multisim environment indicate that the system has improved dependability. It maintains a high level of accuracy in a stable condition, with no static error and a reaction time of 1.5 ms, without any overshooting. The effectiveness of the optimum PIDF control in regulating the DCM Boost Converter is highlighted by the system's strong ability to handle changes in load during transient states within a time frame of 300 ms. This study represents a substantial enhancement compared to conventional PID-based approaches, providing valuable knowledge about the possible uses in power electronics and control systems.

Remote coupling of electrical and mechanical cues by diurnal photothermal irradiation synergistically promotes bone regeneration.

Recapitulating the natural extracellular physical microenvironment has emerged as a promising method for tissue regeneration, as multiple physical interventions, including ultrasound, thermal and electrical therapy, have shown great potential. However, simultaneous coupling of multiple physical cues to highly bio-mimick natural characteristics for improved tissue regeneration still remains formidable. Coupling of intrinsic electrical and mechanical cues has been regarded as an effective way to modulate tissue repair. Nevertheless, precise and convenient manipulation on coupling of mechano-electrical signals within extracellular environment to facilitate tissue regeneration remains challengeable. Herein, a photothermal-sensitive piezoelectric membrane was designed for simultaneous integration of electrical and mechanical signals in response to NIR irradiation. The high-performance mechano-electrical coupling under NIR exposure synergistically triggered the promotion of osteogenic differentiation of stem cells and enhances bone defect regeneration by increasing cellular mechanical sensing, attachment, spreading and cytoskeleton remodeling. This study highlights the coupling of mechanical signals and electrical cues for modulation of osteogenesis, and sheds light on alternative bone tissue engineering therapies with multiple integrated physical cues for tissue repair.

Exploring advanced 2D acquisitions in breast tomosynthesis: T-shaped and Pentagon geometries.

In this study, we investigate the performance of advanced 2D acquisition geometries - Pentagon and T-shaped - in digital breast tomosynthesis (DBT) and compare them against the conventional 1D geometry. Unlike the conventional approach, our proposed 2D geometries also incorporate anterior projections away from the chest wall. Implemented on the Next-Generation Tomosynthesis (NGT) prototype developed by X-ray Physics Lab (XPL), UPenn, we utilized various phantoms to compare three geometries: a Defrise slab phantom with alternating plastic slabs to study low-frequency modulation; a Checkerboard breast phantom (a 2D adaptation of the Defrise phantom design) to study the ability to reconstruct the fine features of the checkerboard squares; and the 360° Star-pattern phantom to assess aliasing and compute the Fourier-spectral distortion (FSD) metric that assesses spectral leakage and the contrast transfer function. We find that both Pentagon and T-shaped scans provide greater modulation amplitude of the Defrise phantom slabs and better resolve the squares of the Checkerboard phantom against the conventional scan. Notably, the Pentagon geometry exhibited a significant reduction in aliasing of spatial frequencies oriented in the right-left (RL) medio-lateral direction, which was corroborated by a near complete elimination of spectral leakage in the FSD plot. Conversely T-shaped scan redistributes the aliasing between both posteroanterior (PA) and RL directions thus maintaining non-inferiority against the conventional scan which is predominantly affected by PA aliasing. The results of this study underscore the potential of incorporating advanced 2D geometries in DBT systems, offering marked improvements in imaging performance over the conventional 1D approach.

Current Concepts in the Epigenetic Regulation of Cardiac Fibrosis.

Cardiac fibrosis is a significant driver of congestive heart failure, a syndrome that continues to affect a growing patient population globally. Cardiac fibrosis results from a constellation of complex processes at the transcription, receptor, and signaling axes levels. Various mediators and signaling cascades, such as the transformation growth factor-beta pathway, have been implicated in the pathophysiology of cardiac tissue fibrosis. Our understanding of these markers and pathways has improved in recent years as more advanced technologies and assays have been developed, allowing for better delineation of the crosstalk between specific factors. There is mounting evidence suggesting that epigenetic modulation plays a pivotal role in the progression of cardiac fibrosis. Transcriptional regulation of key pro- and anti-fibrotic pathways can accentuate or blunt the rate and extent of fibrosis at the tissue level. Exosomes, micro-RNAs, and long non-coding RNAs all belong to factors that can impact the epigenetic signature in cardiac fibrosis. Herein, we comprehensively review the latest literature about exosomes, their contents, and cardiac fibrosis. In doing so, we highlight the specific transcriptional factors with pro- or anti-fibrotic properties. We also assimilate the data supporting these mediators' potential utility as diagnostic or prognostic biomarkers. Finally, we offer insight into where further work can be done to fill existing gaps to translate pre-clinical findings better and improve clinical outcomes.

Efficient and stable NIR-II phosphorescence of metallophilicmolecular oligomers for in vivo single-cell tracking and time-resolved imaging.

Molecular phosphorescence in the second near-infrared window (NIR-II, 1000-1700 nm) holds promise for deep-tissue optical imaging with high contrast by overcoming background fluorescence interference. However, achieving bright and stable NIR-II molecular phosphorescence suitable for biological applications remains a formidable challenge. Herein, we report a new series of symmetric isocyanorhodium(I) complexes that could form oligomers and exhibit bright, long-lived (7-8 µs) phosphorescence in aqueous solution via metallophilic interaction. Ligand substituents with enhanced dispersion attraction and electron-donating properties were explored to extend excitation/emission wavelengths and enhanced stability. Further binding the oligomers with fetal bovine serum (FBS) resulted in NIR-II molecular phosphorescence with high quantum yields (up to 3.93%) and long-term stability in biological environments, enabling in vivo tracking of single-macrophage dynamics and high-contrast time-resolved imaging. These results pave the way for the development of highly-efficient NIR-II molecular phosphorescence for biomedical applications.

S-allyl-cysteine triggers cytotoxic events in rat glioblastoma RG2 and C6 cells and improves the effect of temozolomide through the regulation of oxidative responses.

Glioblastoma (GBM) is an aggressive form of cancer affecting the Central Nervous System (CNS) of thousands of people every year. Redox alterations have been shown to play a key role in the development and progression of these tumors as Reactive Oxygen Species (ROS) formation is involved in the modulation of several signaling pathways, transcription factors, and cytokine formation. The second-generation oral alkylating agent temozolomide (TMZ) is the first-line chemotherapeutic drug used to treat of GBM, though patients often develop primary and secondary resistance, reducing its efficacy. Antioxidants represent promising and potential coadjutant agents as they can reduce excessive ROS formation derived from chemo- and radiotherapy, while decreasing pharmacological resistance. S-allyl-cysteine (SAC) has been shown to inhibit the proliferation of several types of cancer cells, though its precise antiproliferative mechanisms remain poorly investigated. To date, SAC effects have been poorly explored in GBM cells. Here, we investigated the effects of SAC in vitro, either alone or in combination with TMZ, on several toxic and modulatory endpoints-including oxidative stress markers and transcriptional regulation-in two glioblastoma cell lines from rats, RG2 and C6, to elucidate some of the biochemical and cellular mechanisms underlying its antiproliferative properties. SAC (1-750 µM) decreased cell viability in both cell lines in a concentration-dependent manner, although C6 cells were more resistant to SAC at several of the tested concentrations. TMZ also produced a concentration-dependent effect, decreasing cell viability of both cell lines. In combination, SAC (1 µM or 100 µM) and TMZ (500 µM) enhanced the effects of each other. SAC also augmented the lipoperoxidative effect of TMZ and reduced cell antioxidant resistance in both cell lines by decreasing the TMZ-induced increase in the GSH/GSSG ratio. In RG2 and C6 cells, SAC per se had no effect on Nrf2/ARE binding activity, while in RG2 cells TMZ and the combination of SAC + TMZ decreased this activity. Our results demonstrate that SAC, alone or in combination with TMZ, exerts antitumor effects mediated by regulatory mechanisms of redox activity responses. SAC is also a safe drug for testing in other models as it produces non-toxic effects in primary astrocytes. Combined, these effects suggest that SAC affords antioxidant properties and potential antitumor efficacy against GBM.

Design and implementation of an innovative single-phase direct AC-AC bipolar voltage buck converter with enhanced control topology.

Direct AC-AC converters are strong candidates in the power converting system to regulate grid voltage against the perturbation in the line voltage and to acquire frequency regulation at discrete step levels in variable speed drivers for industrial systems. All such applications require the inverted and non-inverted form of the input voltage across the output with voltage-regulating capabilities. The required value of the output frequency is gained with the proper arrangement of the number of positive and negative pulses of the input voltage across the output terminals. The period of each such pulse for low-frequency operation is almost the same as the half period of the input grid or utility voltage. These output pulses are generated by converting the positive and negative input half cycles in noninverting and inverting forms as per requirement. There is no control complication to generate control signals used to adjust the load frequency as the operating period of the switching devices is normally greater than the period of the source voltage. However, high-frequency pulse width modulated (PWM) control signals are used to regulate the output voltage. The size of the inductor and capacitor is inversely related to the value of the switching frequency. Similarly, the ripple contents of voltage and currents in these filtering components are also inversely linked with PWM frequency. These constraints motivate the circuit designer to select high PWM frequency. However, the alignment of the high-frequency control input with the variation in the input source voltage is a big challenge for a design engineer as the switching period of a high-frequency signal normally lies in the microsecond. It is also required to operate some high-frequency devices for various half cycles of the source voltage, creating control complications as the polarities of the half cycles are continuously changing. This requires at least the generation of two high-frequency signals for different intervals. The interruption of the filtering inductor current is a big source of high voltage surges in circuits where the high-frequency transistors operate in a complementary way. This may be due to internal defects in the switching transistors or some unnecessary inherent delay in their control signals. In this research work, a simplified AC-AC converter is developed that does not need alignment of high-frequency control with the polarity of the source voltage. With this approach, high-frequency signals can be generated with the help of any analog or digital control system. By applying this technique, only one high-frequency control signal is generated and applied in AC circuits, as in a DC converter, without applying a highly sensitive polarity sensing circuit. So, controlling complications is drastically simplified. The circuit and configuration always avoid the current interruption problem of filtering the inductor. The proposed control and circuit topology are tested both in computer-based simulation and practically developed circuits. The results obtained from these platforms endorse the effectiveness and validation of the proposed work.

Modulated turbulent convection: a benchmark model for large scale natural flows driven by diurnal heating.

Our life is strongly affected by turbulent convective flows, driven by time-dependent thermal forcing, especially diurnal heating of the Earth's surface by the Sun. In a laboratory experiment, we investigate their analogues: We study complex and extraordinary properties of turbulent buoyancy driven flows generated due to periodic modulation of the temperature of the plates of a Rayleigh-Bénard cell, with amplitudes both smaller and larger than either the positive or negative mean temperature difference between the top and bottom. We probe the turbulent flow of our working fluid - cryogenic helium gas - using temperature sensors placed in the cell interior and embedded in its plates. We discuss spatial and temporal structure of the heat flow, generalize validity of Nusselt versus Rayleigh number scaling Nu ∝ Ra γ with γ ≈ 1 / 3 at very high Ra for modulated convection and argue that this system represents a benchmark model which helps us understand the energy budget of ocean currents or weather formation on Earth subject to diurnal Sun heating as well as similar natural flows on Earth-like planets.