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At least 613 records · Page 34

MiR-374b-5p-FOXP1 feedback loop regulates cell migration, epithelial-mesenchymal transition and chemosensitivity in ovarian cancer

MicroRNAs (miRNAs) are important regulators in tumorigenesis and progression of multiple human cancers, including ovarian cancer (OC). As a member of miRNAs family, miR-374b-5p has been reported to be a tumor suppressive gene in human cancers. In this study, the lower expression of miR-374b-5p was identified in OC tissues and cell liens using quantitative real time PCR (qRT-PCR). Forkhead box protein P1 (FOXP1) can act as an oncogene in human cancers. Mechanism experiments revealed that FOXP1 is a target of miR-374b-5p. Functionally, miR-374b-5p suppressed cell proliferation, migration and epithelial-mesenchymal transition (EMT) in ovarian cancer. Moreover, the sensitivity of OC cells to cisplatin was markedly enhanced by miR-374b-5p. However, FOXP1 reversed However, FOXP1 reversed miR-374b-5p-mediated biological functions. Previous reports demonstrated the inhibitory effect of FOXP1 on transcription FOXP1. Thus, we further examined the effect of FOXP1 on the transcription activity of miR-374b-5p in OC cells. The results showed that FOXP1 decreased miR-374b-5p expression by inhibiting the transcription activity of miR-374b-5p. Rescue assays revealed the regulatory effect of miR-374b-5p-FOXP1 feedback loop on ovarian cancer progression. In conclusion, miR-374b-5p-FOXP1 feedback loop regulates tumor progression and chemosensitivity in ovarian cancer.

60 APPLIED LIFE SCIENCES↗

LncRNA ZEB1-AS1/miR-409–3p/ZEB1 feedback loop is involved in the progression of non-small cell lung cancer

Highlights: • ZEB1-AS1 was increase in NSCLC cells and ZEB1-AS1 silencing inhibited cell proliferation and induced apoptosis. • ZEB1-AS1 positively regulates ZEB1 through sponging miR-409–3p. • ZEB1 could bind to the promoter region of ZEB1-AS1 to activate its expression. • The positive feedback loop of ZEB1-AS1/miR-409–3p/ZEB1 could facilitate the NSCLC oncogenesis. Emerging evidence has illustrated that long noncoding RNA (LncRNA) ZEB1 antisense RNA 1 (ZEB1-AS1) involved in the development of various type of human cancers. However, the role of ZEB1-AS1 in non-small cell lung cancer (NSCLC) is still elusive and poorly understood. The present study aimed to provide functional evidence and elucidate the molecular mechanisms by which the ZEB1-AS1 promotes oncogenesis of NSCLC. Our study found that ZEB1-AS1 was upregulated in NSCLC cells and knockdown of ZEB1-AS1 significantly inhibited cell growth and induced cell apoptosis. Mechanically, miR-409–3p was confirmed as a direct target of ZEB1-AS1 and negatively regulated by ZEB1-AS1 via competing endogenous RNA (ceRNA) mechanism; miR-409–3p inhibited ZEB1 expression by directly binding to the 3′UTR. Importantly, as predicted by JASPAR and further confirmed by luciferase reporter gene and ChIP assays, we found ZEB1 could bind to the promoter region of ZEB1-AS1 to activate its expression. Restoration of ZEB1 could partially abolished the action of ZEB1-AS1 silencing on cell proliferation and apoptosis. Collectively, the results suggested that ZEB1-AS1/miR-409–3p/ZEB1 constitutes a positive feedback loop to promote the tumorigenesis of NSCLC, highlighting the possibility of improving NSCLC treatment by targeting the ZEB1-AS1 signaling pathway.

60 APPLIED LIFE SCIENCES↗

Visual feedback and guided balance training in an immersive virtual reality environment for lower extremity rehabilitation

Balance training is essential for physical rehabilitation procedures, as it can improve functional mobility and enhance cognitive coordination. However, conventional balance training methods may have limitations in terms of motivation, real-time objective feedback, and personalization, which a virtual reality (VR) setup may provide a better alternative. In this work, we present an immersive VR training environment for lower extremity balance rehabilitation with real-time guidance and feedback. The VR training environment immerses the user in a 3D ice rink model where a virtual coach (agent) leads them through a series of balance poses, and the user controls a trainee avatar with their own movements. Here we developed two coaching styles: positive-reinforcement and autonomous-supportive, and two viewpoints of the trainee avatar: first-person and third-person. The proposed environment was evaluated in a user study with healthy, non-clinical participants (n = 16, 24.4 ± 5.7 years old, 9 females). Our results show that participants showed stronger performance in the positive-reinforcement style compared to the autonomous-supportive style. Additionally, in the third-person viewpoint, the participants exhibited more stability in the positive-reinforcement style compared to the autonomous-supportive style. For viewpoint, participants exhibited stronger performance in the first-person viewpoint compared to third-person in the autonomous-supportive style, while they were comparable in the positive-reinforcement style. We observed no significant effects on the foot height and number of mistakes. Furthermore, we report the analysis of user performance with balance training poses and subjective measures based on questionnaires to assess the user experience, usability, and task load. The proposed VR balance training could offer an interactive, adaptive, and engaging environment and open new potential research directions for lower extremity rehabilitation.

97 MATHEMATICS AND COMPUTING↗

A self-learning disturbance observer for nonlinear systems in feedback-error learning scheme

Here this paper represents a novel online self-learning disturbance observer (SLDO) by benefiting from the combination of a type-2 neuro-fuzzy structure (T2NFS), feedback-error learning scheme and sliding mode control (SMC) theory. The SLDO is developed within a framework of feedback-error learning scheme in which a conventional estimation law and a T2NFS work in parallel. In this scheme, the latter learns uncertainties and becomes the leading estimator whereas the former provides the learning error to the T2NFS for learning system dynamics. A learning algorithm established on SMC theory is derived for an interval type-2 fuzzy logic system. In addition to the stability of the learning algorithm, the stability of the SLDO and the stability of the overall system are proven in the presence of time-varying disturbances. Thanks to learning process by the T2NFS, the simulation results show that the SLDO is able to estimate time-varying disturbances precisely as distinct from the basic nonlinear disturbance observer (BNDO) so that the controller based on the SLDO ensures robust control performance for systems with time-varying uncertainties, and maintains nominal performance in the absence of uncertainties.

42 ENGINEERING↗

Feedback Control Approaches for Restoration of Power Grids from Blackouts

The automated restoration of power systems with variable energy resources is a timely problem to tackle. Automated restoration advice can support operators in deciding on strategic actions to restore power grids from a blackout with a mix of conventional and renewable generation resources. To this end, this paper frames the restoration process of power grids with solar resources as a nonlinear dynamic model with algebraic constraints in discrete time which is steered by feedback control loops. We discuss two feedback-control strategies based on greedy and reinforcement learning algorithms, and contrast their performance with restoration plans generated by a mixed-integer linear program. We found that the reinforcement learning algorithm infers restoration actions faster than the greedy one. However, the tuning process of the reinforcement learning parameters is slower than for the greedy one.

machine learning↗

Feedforward-feedback ammonia control at a water resource recovery facility based on a digital twin with hybrid model

Ammonia-based aeration control (ABAC) at full-scale Water Resource Recovery Facilities (WRRFs) can be challenged by diurnal loading and transport delays. This work addressed these challenges using a hybrid feedforward–feedback controller built on Activated Sludge Model 1 (ASM1), marking the first full-scale deployment to pair a mechanistic feedforward core with data-driven corrections. The objectives were to improve ammonia setpoint tracking, assess performance of the mechanistic model when enhanced with data-driven corrections, and document full-scale operation. The hybrid model incorporates two data-driven components: (1) a Mechanistic Error Forecasting Engine (MEFE), consisting of a multivariate linear regressor and a long short-term memory (LSTM) ensemble. Defying expectations, low-parameter models outperformed more complex alternatives, reducing the mechanistic error by 71%. (2) A Residual Oscillation Forecasting Engine (ROFE), based on Fast Fourier Transform, reduced the remaining error by another 35%. Two proportional–integral (PI) feedback loops further (i) trim the feedforward output and (ii) eliminate residual controller error in the final aerobic zone. In full-scale operation, the controller reduced mean-squared error (MSE) by 94% over the baseline and produced more stable dissolved oxygen (DO) setpoints. Overall, it was proven that layering multi-timescale data-driven models on a mechanistic core can yield reliable ABAC performance at WRRFs.

54 ENVIRONMENTAL SCIENCES↗

Adaptive model tuning studies for non-invasive diagnostics and feedback control of plasma wakefield acceleration at FACET-II

Beam-driven plasma wakefield acceleration (PWFA) achieves the same energy gain in a single meter, for which conventional accelerators require several kilometers, however much work is still required to match the beam quality of conventional accelerators. The PWFA processes to be studied at the FACET-II facility will utilize extremely short (down to a few fs) high energy (10 GeV), high charge (few nC) electron and eventually positron bunches. The PWFA process is extremely sensitive to the detailed longitudinal current profiles of these bunches and it would be of great benefit to have precise measurement and control of these profiles. We present an adaptive model tuning technique for FACET-II to adaptively tune online models based on real time accelerator and beam data to continuously provide a non-invasive diagnostic which predicts the longitudinal phase space (LPS) of extremely short and highly compressed electron beams, which otherwise require destructive X-band transverse deflecting cavity (XTCAV)-based measurements. Based on simulation studies, our method has the potential for: (1). The development of a non-invasive longitudinal phase space diagnostic by adaptively tuning models based on non-invasive measurements such as energy spread spectra which could be recorded at all of the bunch compressors in the facility. (2). Utilize these diagnostic to perform model-independent feedback-based to achieve desired longitudinal phase space distributions. (3). Utilize the model-independent feedback approach to maximize energy gain while minimizing emittance growth and energy gain variance of the PWFA process by tuning accelerator parameters, while monitoring what longitudinal phase space the algorithm has found, information that will be useful for further analytical and simulation studies.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Negative feedback regulation of Homer 1a on norepinephrine-dependent cardiac hypertrophy

Homers are scaffolding proteins that modulate diverse cell functions being able to assemble signalling complexes. In this study, the presence, sub-cellular distribution and function of Homer 1 was investigated. Homer 1a and Homer 1b/c are constitutively expressed in cardiac muscle of both mouse and rat and in HL-1 cells, a cardiac cell line. As judged by confocal immunofluorescence microscopy, Homer 1a displays sarcomeric and peri-nuclear localization. In cardiomyocytes and cultured HL-1 cells, the hypertrophic agonist norepinephrine (NE) induces α{sub 1}-adrenergic specific Homer 1a over-expression, with a two-to-three-fold increase within 1 h, and no up-regulation of Homer 1b/c, as judged by Western blot and qPCR. In HL-1 cells, plasmid-driven over-expression of Homer 1a partially antagonizes activation of ERK phosphorylation and ANF up-regulation, two well-established, early markers of hypertrophy. At the morphometric level, NE-induced increase of cell size is likewise and partially counteracted by exogenous Homer 1a. Under the same experimental conditions, Homer 1b/c does not have any effect on ANF up-regulation nor on cell hypertrophy. Thus, Homer 1a up-regulation is associated to early stages of cardiac hypertrophy and appears to play a negative feedback regulation on molecular transducers of hypertrophy. -- Highlights: • Homer 1a is constitutively expressed in cardiac tissue. • In HL-1 cells, norepinephrine activates signaling pathways leading to hypertrophy. • Homer 1a up-regulation is an early event of norepinephrine-induced hypertrophy. • Homer 1a plays a negative feedback regulation modulating pathological hypertrophy. • Over-expression of Homer 1a per se does not induce hypertrophy.

60 APPLIED LIFE SCIENCES↗

PGC1α regulates mitochondrial oxidative phosphorylation involved in cisplatin resistance in ovarian cancer cells via nucleo-mitochondrial transcriptional feedback

Mitochondria play an important role in effective cell energy production and cell survival under stress conditions, such as treatment with chemotherapeutic drugs. Mitochondrial biogenesis is increased in ovarian cancer tissues, which is accompanied by alteration of mitochondrial energy metabolism, structure, and dynamics. These factors are involved in tumorigenesis and apoptosis resistance, highlighting the role of mitochondria in resisting cisplatin toxicity. Cisplatin-resistant ovarian cancer cells are dependent on mitochondrial OXPHOS for energy supply, and intracellular PGC1α-mediated mitochondrial biogenesis levels are increased in this cell line, indicating the important role of mitochondrial oxidative phosphorylation in cisplatin resistance. As PGC1α is a key molecule for integrating and coordinating nuclear DNA and mitochondrial DNA transcriptional machinery, an investigation into the regulatory mechanism PGC1α in mitochondrial energy metabolism via transcription may provide new clues for solving chemotherapy resistance. In the present study, it was demonstrated that inhibiting the expression of PGC1α decreased nuclear and mitochondrial DNA transcription factor expression, leading to increased lactic acid production and decreased cellular oxygen consumption and mitochondrial oxidative phosphorylation. Furthermore, mitochondrial stress-induced ROS production, as a feedback signal from mitochondria to the cell nucleus, increased PGC1α expression in SKOV3/DDP cells, which was involved in mitochondrial oxidative phosphorylation regulation. Collectively, the present study provides evidence that PGC1α-mediated nuclear and mitochondrial transcription feedback regulates energy metabolism and is involved in ovarian cancer cells escaping apoptosis during cisplatin treatment.

60 APPLIED LIFE SCIENCES↗

Reduction of Feedback Inhibition in Homoserine Kinase (ThrB) of Corynebacterium glutamicum Enhances L -Threonine Biosynthesis

L -Threonine is an important supplement in the food industry. It is currently produced through fermentation of Escherichia coli but requires additional purification steps to remove E. coli endotoxin. To avoid these steps, it is desirable to use Corynebacterium glutamicum , a microorganism generally regarded as safe. Engineering of C. glutamicum to increase production of l -threonine has mainly focused on gene regulation as well as l -threonine export or carbon flux depletion. In this study, we focus on the negative feedback inhibition produced by L -threonine on the enzyme homoserine kinase (ThrB). Although L -threonine binds to allosteric sites of aspartate kinase (LysC) and homoserine dehydrogenase (Hom), serving as a noncompetitive inhibitor, it acts as a competitive inhibitor on ThrB. This is problematic when attempting to engineer enzymes that are nonresponsive to increasing cellular concentrations of L -threonine. Using primary structure alignment as well as analysis of the Methanocaldococcus jannaschii ThrB ( Mja ThrB) active site in complex with L -threonine (inhibitor of ThrB) and L -homoserine (substrate of ThrB), a conserved active-site alanine residue (A20) in C. glutamicum ThrB ( Cgl ThrB) was predicted to be important for differential interactions with L -threonine and L -homoserine. Through site-directed mutagenesis, we show that one variant of C. glutamicum ThrB, Cgl ThrB-A20G, retains wild-type enzymatic activity, with dramatically decreased feedback inhibition by L -threonine. Additionally, by solving the first Corynebacterium X-ray crystal structure of homoserine kinase, we can confirm that the changes in L -threonine affinity to the Cgl ThrB-A20G active site derive from loss of van der Waals interactions.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Observational Evidence of State‐Dependent Positive and Negative Land Surface Feedback on Afternoon Deep Convection Over the Southern Great Plains

Abstract The detection of soil moisture‐precipitation feedback is complicated by the dependence of feedback sign on atmospheric state and cloud types. We evaluated responses of convective clouds to changes in surface evaporative fraction (EF) from satellite and ground‐based measurements over the Southern Great Plains in summer months. Strong responses to EF were inferred only after accounting for tropospheric states supporting systematically positive or negative responses. State dependence (inferred from controlled model experiments) explains the weak response found in previous studies. The probability of transitions from shallow to deep cumulus, and subsequent precipitation onset, increases by 58% over drier surfaces in weakly stratified environments having deeper boundary layers. Boundary layer dynamics play a more important role than low‐level relative humidity in these environments. Wetter surfaces yield increased deep convection in moist and thermally stratified environments. The distinct pathways of convective initiation over dry and wet land surfaces can play important roles in drought onset and termination.

Qiu, Shaoyue↗

Warm Phase of AMV Damps ENSO Through Weakened Thermocline Feedback

Abstract Interactions between ocean basins affect El Niño–Southern Oscillation (ENSO), altering its impacts on society. Here, we explore the effect of Atlantic Multidecadal Variability (AMV) on ENSO behavior using idealized experiments performed with the NCAR‐CESM1 model. Comparing warm (AMV+) to cold (AMV−) AMV conditions, we find that ENSO sea surface temperature (SST) anomalies are reduced by ∼10% and ENSO precipitation anomalies are shifted to the west during El Niño and east during La Niña. Using the Bjerknes stability index, we attribute the reduction in ENSO variability to a weakened thermocline feedback in boreal autumn. In AMV+, the Walker circulation and trade winds strengthen over the tropical Pacific, increasing the background zonal SST gradient. The background changes shift ENSO anomalies westwards, with wind stress anomalies more confined to the west. We suggest the changes in ENSO‐wind stress decrease the strength of the thermocline feedback in the east, eventually reducing ENSO growth rate.

Trascasa‐Castro, Paloma↗

The Role of Mesoscale Cloud Morphology in the Shortwave Cloud Feedback

A supervised neural network algorithm is used to categorize near-global satellite retrievals into three mesoscale cellular convective (MCC) cloud morphology patterns. At constant cloud amount, morphology patterns differ in brightness associated with the amount of optically thin cloud features. Environmentally driven transitions from closed MCC to other morphology patterns, typically accompanied by more optically thin cloud features, are used as a framework to quantify the morphology contribution to the optical depth component of the shortwave cloud feedback. A marine heat wave is used as an out-of-sample test of closed MCC occurrence predictions. Morphology shifts in optical depth between 65°S and 65°N under projected environmental changes (i.e., from an abrupt quadrupling of CO 2 ) assuming constant cloud cover contributes between 0.04 and 0.07 W m -2 K -1 (aggregate of 0.06) to the global mean cloud feedback.

54 ENVIRONMENTAL SCIENCES↗

The Shortwave Cloud-SST Feedback Amplifies Multi-Decadal Pacific Sea Surface Temperature Trends: Implications for Observed Cooling

Climate models struggle to produce sea surface temperature (SST) gradient trends in the tropical Pacific comparable to those seen recently in nature. Here, we find that the magnitude of the cloud-SST feedback in the subtropical Southeast Pacific is correlated across models with the magnitude of Eastern Pacific multi-decadal SST variability. A heat-budget analysis reveals coupling between cloud-radiative effects, circulation, and SST gradients in driving multi-decadal variability in the Eastern Pacific. Using this relationship and observed feedback estimates, we find that internal Eastern Pacific SST variability is underestimated in most models. Adjusting for model bias increases the likelihood of generating a cooling trend at least as large as observations in preindustrial control simulations by ~56% on average. If models underestimate climate “noise,” as our results suggest, this bias should be accounted for when attributing the relative importance of forced versus unforced changes in the climate.

58 GEOSCIENCES↗

Climate mitigation from vegetation biophysical feedbacks during the past three decades

The surface air temperature response to vegetation changes has been studied for the extreme case of land-cover change; yet, it has never been quantified for the slow but persistent increase in leaf area index (LAI) observed over the past 30 years (Earth greening). We isolate the fingerprint of increasing LAI on surface air temperature using a coupled land–atmosphere global climate model prescribed with satellite LAI observations. Furthermore, we found that the global greening has slowed down the rise in global land-surface air temperature by 0.09 ± 0.02 °C since 1982. This net cooling effect is the sum of cooling from increased evapotranspiration (70%), changed atmospheric circulation (44%), decreased shortwave transmissivity (21%), and warming from increased longwave air emissivity (-29%) and decreased albedo (-6%). The global cooling originated from the regions where LAI has increased, including boreal Eurasia, Europe, India, northwest Amazonia, and the Sahel. Increasing LAI did not, but, significantly change surface air temperature in eastern North America and East Asia, where the effects of large-scale atmospheric circulation changes mask local vegetation feedbacks. Overall, the sum of biophysical feedbacks related to the greening of the Earth mitigated 12% of global land-surface warming for the past 30 years.

54 ENVIRONMENTAL SCIENCES↗

Diminishing seasonality of subtropical water availability in a warmer world dominated by soil moisture–atmosphere feedbacks

Global warming is expected to cause wet seasons to get wetter and dry seasons to get drier, which would have broad social and ecological implications. However, the extent to which this seasonal paradigm holds over land remains unclear. Here we examine seasonal changes in surface water availability (precipitation minus evaporation, P–E) from CMIP5 and CMIP6 projections. While the P–E seasonal cycle does broadly intensify over much of the land surface, ~20% of land area experiences a diminished seasonal cycle, mostly over subtropical regions and the Amazon. Using land–atmosphere coupling experiments, we demonstrate that 63% of the seasonality reduction is driven by seasonally varying soil moisture (SM) feedbacks on P–E. Declining SM reduces evapotranspiration and modulates circulation to enhance moisture convergence and increase P–E in the dry season but not in the wet season. Our results underscore the importance of SM–atmosphere feedbacks for seasonal water availability changes in a warmer climate.

54 ENVIRONMENTAL SCIENCES↗

Skin-integrated stretchable actuators toward skin-compatible haptic feedback and closed-loop human-machine interactions

Abstract Skin-integrated haptic interfaces that can relay a wealth of information from the machine to the human are of great interest. However, existing haptic devices are not yet able to produce haptic cues that are compatible with the skin. In this work, we present the stretchable soft actuators for haptic feedback, which can match the perception range, spatial resolution, and stretchability of the skin. Pressure-amplification structures are fabricated using a scalable self-assembly process to ensure an output pressure beyond the skin perception threshold. Due to the minimized device size, the actuator array can be fabricated with a sufficiently high spatial resolution, which makes the haptic device applicable for skin locations with the highest spatial acuity. A haptic feedback system is demonstrated by employing the developed soft actuators and highly sensitive pressure sensors. Two proof-of-concept applications are developed to illustrate the capability of transferring information related to surface textures and object shapes acquired at the robot side to the user side.

Chen, Si↗

Multichannel haptic feedback unlocks prosthetic hand dexterity

Abstract Loss of tactile sensations is a major roadblock preventing upper limb-absent people from multitasking or using the full dexterity of their prosthetic hands. With current myoelectric prosthetic hands, limb-absent people can only control one grasp function at a time even though modern artificial hands are mechanically capable of individual control of all five digits. In this paper, we investigated whether people could precisely control the grip forces applied to two different objects grasped simultaneously with a dexterous artificial hand. Toward that end, we developed a novel multichannel wearable soft robotic armband to convey artificial sensations of touch to the robotic hand users. Multiple channels of haptic feedback enabled subjects to successfully grasp and transport two objects simultaneously with the dexterous artificial hand without breaking or dropping them, even when their vision of both objects was obstructed. Simultaneous transport of the objects provided a significant time savings to perform the deliveries in comparison to a one-at-a-time approach. This paper demonstrated that subjects were able to integrate multiple channels of haptic feedback into their motor control strategies to perform a complex simultaneous object grasp control task with an artificial limb, which could serve as a paradigm shift in the way prosthetic hands are operated.

60 APPLIED LIFE SCIENCES↗