Control Of Activation Research Articles

Modelling of parallel and series inflatable actuators for sequential activation control

Modelling of parallel and series inflatable actuators for sequential activation control

A novel motorized office chair causes low-amplitude spinal movements and activates trunk muscles: A cross-over trial.

Inactivity and long periods of sitting are common in our society, even though they pose a health risk. Dynamic sitting is recommended to reduce this risk. The purpose of this study was to investigate the effect of continuous passive motion (CPM) conducted by a novel motorized office chair on lumbar lordosis and trunk muscle activation, oxygen uptake and attentional control. Randomized, single-session, crossover with two periods/conditions. Twenty office workers (50% women) sat for one hour on the motorized chair, one half with CPM, the other not. The starting condition (CPM/no CPM) was switched in half of the sample. The participants were equipped with a spirometric cart, surface EMG, the Epionics SPINE system and performed a computer-based test for attentional control (AX-CPT). Outcomes were lumbar sagittal movements and posture, number of trunk muscle activations, attentional control and energy expenditure. The CPM of the chair causes frequent low-amplitude changes in lumbar lordosis angle (moved: 498 ± 133 vs. static: 45 ± 38) and a higher number of muscle activations. A periodic movement pattern of the lumbar spine according to the movement of the chair was observed in every participant, although, sitting behavior varied highly between individuals. Attentional control was not altered in the moved condition (p = .495; d = .16). Further, oxygen uptake did not increase higher than 1.5 MET. The effects of the motorized chair can be particularly useful for people with static sitting behavior. Further studies should investigate, whether CPM provides the assumed beneficial effects of dynamic sitting on the spine.

Cognitive Patterns and Problematic Use of Video Games in Adolescents: A Cluster Analysis.

Video game playing (VGP) is an increasingly common leisure activity among children and adolescents, although in some cases, it is accompanied by problems due to misuse. A sample of 2884 children and adolescents aged between 12 and 20, representative of the Community of Madrid (Spain), were studied using a cluster analysis to explore the existence of cognitive patterns associated with engagement, attitudes, and concurrent cognitions. We also explored the relationship between these patterns and problematic VGP, using the 2173 gamers as a reference. The concurrent cognitions were not qualitatively different between the problematic users and the others. High engagement and high activation of concurrent cognitions (intensity and frequency) showed the greatest relationship with problematic VGP. The results suggest the existence of different groups of gamers and the relevance to include psycho-educational aspects in intervention programs, as well as the training of specific skills, especially those related with the control of activation. Limitations related to the sample size and potential supplementary analyses are acknowledged.

Stereoselective Control of the Cu Activation of β,β-Diboryl Acrylates for Allylic Coupling Protocols with Concomitant Lactonization.

The key to a successful C-B activation is to discriminate between two geminal boryl moieties that are exposed to the same reaction conditions. Here we describe a stereoselective C-B activation of β,β-diboryl acrylates forming exclusively the (Z)-α-borylalkenyl copper(I) key intermediate, for subsequent allylic alkylation reactions. The new borylated (Z)-skipped dienoates followed a feasible iodo-lactonization sequence for the preparation of borylated lactone cores, which can be used in drug discovery.

Biorational control of corn leafhopper and activation of resistance with compounds from Morinda citrifolia.

Currently, the increasing productivity, garanee phytosanitary measures, and food security in plantations is a significant challenge. The potential of plant compounds in pests and diseases alternative control has been widely researched. This study is the first to investigate the use of the plant Morinda citrifolia L.(noni) for managing maize leafhoppers, a major issue in plantations. The effects of essential oil and octanoic acid on resistance induction were evaluated with quantification of phytoalexins, potential phytotoxicity, and toxicity to corn leafhopper, Dalbulus maidis. The chromatographic analysis identified octanoic acid as the primary compound, constituting 58.43% of the essential oil. The elicitor potential was more pronounced in plants treated with M. citrifolia compounds than in those treated with commercial resistance-activating products. The essential oil effectively controlled D. maidis, resulting in 50% mortality after 48 hours without damaging the leaf area. These findings highlight the potential of M. citrifolia in the biorational control of the stunting complex, with effective vector control and resistance induction.

PROTEIN RAS-LIKE PROTEINS FROM RAT BRAIN SEBAGAI TARGET PENGHAMBATAN PERKEMBANGAN SEL KANKER

Ras-like proteins from rat brain (Rab) is one of the crucial proteins in the process of intracellular transport. Rab plays a role in delivering vesicles from the donor membrane to the acceptor membrane. Vesicles contain various molecules that are important in cell growth and development. These molecules are generally involved in some signaling pathways. In carrying out its functions, Rab needs to be activated first. The activation process of Rab involves various proteins. Thus, Rab activation and deactivation control are critical to regulating the movement of the transferred molecules. In cancer, there is an uncontrolled activation and deactivation of Rab. Rab's involvement in various signaling pathways by providing molecules needed for growth and development is a basis for increasing the speed of growth and development of cancer cells. Although Rab is not the main factor causing cancer, it can help the development of cancer. So, it can be one of the keys to controlling the transfer of molecules involved in the growth and development of cancer cells. There are several methods related to the activation of Rab for molecular transport. Rab activation inhibition by Rab inhibitors and inhibitors of Rab activating proteins and the use of miRNAs can prevent molecule transport. Thus, control of Rab activation can be an alternative to suppress the growth and development of cancer cells.

Bexmarilimab-induced macrophage activation leads to treatment benefit in solid tumors: The phase I/II first-in-human MATINS trial

Macrophage Clever-1 contributes to impaired antigen presentation and suppression of anti-tumor immunity. This first-in-human trial investigates the safety and tolerability of Clever-1 blockade with bexmarilimab in patients with treatment-refractory solid tumors and assesses preliminary anti-tumor efficacy, pharmacodynamics, and immunologic correlates. Bexmarilimab shows no dose-limiting toxicities in part I (n= 30) and no additional safety signals in part II (n= 108). Disease control (DC) rates of 25%-40% are observed in cutaneous melanoma, gastric, hepatocellular, estrogen receptor-positive breast, and biliary tract cancers. DC associates with improved survival in a landmark analysis and correlates with high pre-treatment intratumoral Clever-1 positivity and increasing on-treatment serum interferon γ (IFNγ) levels. Spatial transcriptomics profiling of DC and non-DC tumors demonstrates bexmarilimab-induced macrophage activation and stimulation of IFNγ and Tcell receptor signaling selectively in DC patients. These data suggest that bexmarilimab therapy is well tolerated and show that macrophage targeting can promote immune activation and tumor control in late-stage cancer.

Halogen-Site Regulation in Cs3Bi2X9 Quantum Dots for Efficient and Selective Oxidation of Benzyl Alcohol Driven by Solar Light.

Sluggish charge kinetics and low selectivity limit the solar-driven selective organic transformations under mild conditions. Herein, an efficient strategy of halogen-site regulation, based on the precise control of charge transfer and molecule activation by rational design of Cs3Bi2X9 quantum dots photocatalysts, is proposed to achieve both high selectivity and yield of benzyl-alcohol oxidation. In situ PL spectroscopy study reveals that the Bi─Br bonds formed in the form of Br-associated coordination can enhance the separation and transfer of photoexcited carriers during the practical reaction. As the active center, the exclusive Bi─Br covalence can benefit the benzyl-alcohol activation for producing carbon-centered radicals. As a result, the Cs3Bi2Br9 with this atomic coordination achieves a conversion ratio of 97.9% for benzyl alcohol and selectivity of 99.6% for aldehydes, which are 56.9- and 1.54-fold higher than that of Cs3Bi2Cl9. Combined with quasi-in situ EPR, in situ ATR-FTIR spectra, and DFT calculation, the conversion of C6H5-CH2OH to C6H5-CH2* at Br-related coordination is revealed to be a determining step, which can be accelerated via halogen-site regulation for enhancing selectivity and photocatalytic efficiency. The mechanistic insights of this research elucidate how halogen-site regulation in favor of charge transfer and molecule activation toward efficient and selective oxidation of benzyl alcohol.

Movement predictability modulates sensorimotor processing.

An important factor for optimal sensorimotor control is how well we are able to predict sensory feedback from internal and external sources during movement. If predictability decreases due to external disturbances, the brain is able to adjust muscle activation and the filtering of incoming sensory inputs. However, little is known about sensorimotor adjustments when predictability is increased by availability of additional internal feedback. In the present study we investigated how modifications of internal and external sensory feedback influence the control of muscle activation and gating of sensory input. Co-activation of forearm muscles, somatosensory evoked potentials (SEP) and short afferent inhibition (SAI) were assessed during three object manipulation tasks designed to differ in the predictability of sensory feedback. These included manipulation of a shared object with both hands (predictable coupling), manipulation of two independent objects without (uncoupled) and with external interference on one of the objects (unpredictable coupling). We found a task-specific reduction in co-activation during the predictable coupling compared to the other tasks. Less sensory gating, reflected in larger subcortical SEP amplitudes, was observed in the unpredictable coupling task. SAI behavior was closely linked to the subcortical SEP component indicating an important function of subcortical sites in predictability related SEP gating and their direct influence on M1 inhibition. Together, these findings suggest that the unpredictable coupling task cannot only rely on predictive forward control and is compensated by enhancing co-activation and increasing the saliency for external stimuli by reducing sensory gating at subcortical level. This behavior might serve as a preparatory step to compensate for external disturbances and to enhance processing and integration of all incoming external stimuli to update the current sensorimotor state. In contrast, predictive forward control is accurate in the predictable coupling task due to the integrated sensory feedback from both hands where sensorimotor resources are economized by reducing muscular co-activation and increasing sensory gating.

FOXO1 reduces STAT3 activation and causes impaired mitochondrial quality control in diabetic cardiomyopathy.

To investigate the role of FOXO1 in STAT3 activation and mitochondrial quality control in the diabetic heart. Type 1 diabetes mellitus (T1DM) was induced in rats by a single intraperitoneal injection of 60 mg · kg-1 streptozotocin (STZ), while type 2 diabetes mellitus (T2DM) was induced in rats with a high-fat diet through intraperitoneal injection of 35 mg · kg-1 STZ. Primary neonatal mouse cardiomyocytes and H9c2 cells were exposed to low glucose (5.5 mM) or high glucose (HG; 30 mM) with or without treatment with the FOXO1 inhibitor AS1842856 (1 μM) for 24 hours. In addition, the diabetic db/db mice (aged 8 weeks) and sex- and age-matched non-diabetic db/+ mice were treated with vehicle or AS1842856 by oral gavage for 15 days at a dose of 5 mg · kg-1 · d-1 . Rats with T1DM or T2DM had excessive cardiac FOXO1 activation, accompanied by decreased STAT3 activation. Immunofluorescence and immunoprecipitation analysis showed colocalization and association of FOXO1 and STAT3 under basal conditions in isolated cardiomyocytes. Selective inhibition of FOXO1 activation by AS1842856 or FOXO1 siRNA transfection improved STAT3 activation, mitophagy and mitochondrial fusion, and decreased mitochondrial fission in isolated cardiomyocytes exposed to HG. Transfection with STAT3 siRNA further reduced mitophagy, mitochondrial fusion and increased mitochondrial fission in HG-treated cardiomyocytes. AS1842856 alleviated cardiac dysfunction, pathological damage and improved STAT3 activation, mitophagy and mitochondrial dynamics in diabetic db/db mice. Additionally, AS1842856 improved mitochondrial function indicated by increased mitochondrial membrane potential and adenosine triphosphate production and decreased mitochondrial reactive oxygen species production in isolated cardiomyocytes exposed to HG. Excessive FOXO1 activation during diabetes reduces STAT3 activation, with subsequent impairment of mitochondrial quality, ultimately promoting the development of diabetic cardiomyopathy.

MARCH5 promotes STING pathway activation by suppressing polymer formation of oxidized STING.

Stimulator of interferon genes (STING) is a core DNA sensing adaptor in innate immune signaling. STING activity is regulated by a variety of post-translational modifications (PTMs), including phosphorylation, ubiquitination, sumoylation, palmitoylation, and oxidation, as well as the balance between active and inactive polymer formation. It remains unclear, though, how different PTMs and higher order structures cooperate to regulate STING activity. Here, we report that the mitochondrial ubiquitin ligase MARCH5 (Membrane Associated Ring-CH-type Finger 5, also known as MITOL) ubiquitinates STING and enhances its activation. A long-term MARCH5 deficiency, in contrast, leads to the production of reactive oxygen species, which then facilitate the formation of inactive STING polymers by oxidizing mouse STING cysteine 205. We show that MARCH5-mediated ubiquitination of STING prevents the oxidation-induced STING polymer formation. Our findings highlight that MARCH5 balances STING ubiquitination and polymer formation and its control of STING activation is contingent on oxidative conditions.

Light-responsive smart nanocarriers for wirelessly controlled photodynamic therapy for prostate cancers.

Photodynamic therapy (PDT) is an effective non-invasive or minimally invasive treatment method against different tumors. Loading photosensitizers in nanocarriers can potentially increase their accumulation in tumor sites. However, the PDT efficacy may be hindered because of self-quenching of the encapsulated photosensitizer and the small diffusion radii of the generated reactive oxygen species (ROS). Herein, light responsive nano assemblies composed of (Polyethylene glycol)-block-poly(4,5-dimethoxy-2-nitrobenzylmethacrylate) (PEG-b-PNBMA) were designed and loaded with the photosensitizer, Rose Bengal lactone (RB), to act as a smart nanocarrier (RB-M) for the delivery of the photosensitizer. A wirelessly activated light-emitting diode (LED) implant was designed to programmatically induce the release of the loaded RB and activate PDT after diffusion of RB into the cytoplasm. The results showed that sequential '405-580 nm' irradiation of the RB-M treated 22RV1 cells resulted in the highest PDT outcome among different irradiation protocols. The combination of this smart nanocarrier and sequential '405-580 nm' irradiation strategy exhibited good PDT efficacy against 2D 22RV1 prostate cancer cells as well as 3D cancer cell spheroids. This platform overcome the light penetration limitations in PDT, and can potentially be applied in cancer bearing patients who are unfit for chemotherapy. STATEMENT OF SIGNIFICANCE: Nanocarriers for the delivery of photosensitizer in photodynamic therapy may result in relatively low therapeutic efficacy because of self-quenching of the encapsulated photosensitizer and the small diffusion radii of the generated reactive oxygen species (ROS). Light responsive smart nanocarriers can potentially overcome this challenge. In this study, a light responsive polymer (Polyethylene glycol)-block-poly(4,5-dimethoxy-2-nitrobenzylmethacrylate) (PEG-b-PNBMA) was synthesized and utilized to fabricate the smart nanocarrier. A wirelessly activated light-emitting diode (LED) implant was designed for light delivery in deep tissue. This new approach permits wirelessly and programmatically control of photosensitizer release and PDT activation under deep tissue, thus significantly enhancing PDT efficacy against prostate cancer cells as well as 3D cancer cell spheroids. This design should have a significant impact on controllable PDT under deep tissue.

A Multimodel Study of the Role of Novel PKC Isoforms in the DNA Integrity Checkpoint.

The protein kinase C (PKC) family plays important regulatory roles in numerous cellular processes. Saccharomyces cerevisiae contains a single PKC, Pkc1, whereas in mammals, the PKC family comprises nine isoforms. Both Pkc1 and the novel isoform PKCδ are involved in the control of DNA integrity checkpoint activation, demonstrating that this mechanism is conserved from yeast to mammals. To explore the function of PKCδ in a non-tumor cell line, we employed CRISPR-Cas9 technology to obtain PKCδ knocked-out mouse embryonic stem cells (mESCs). This model demonstrated that the absence of PKCδ reduced the activation of the effector kinase CHK1, although it suggested that other isoform(s) might contribute to this function. Therefore, we used yeast to study the ability of each single PKC isoform to activate the DNA integrity checkpoint. Our analysis identified that PKCθ, the closest isoform to PKCδ, was also able to perform this function, although with less efficiency. Then, by generating truncated and mutant versions in key residues, we uncovered differences between the activation mechanisms of PKCδ and PKCθ and identified their essential domains. Our work strongly supports the role of PKC as a key player in the DNA integrity checkpoint pathway and highlights the advantages of combining distinct research models.

How myosin VI traps its off-state, is activated and dimerizes

Myosin VI (Myo6) is the only minus-end directed nanomotor on actin, allowing it to uniquely contribute to numerous cellular functions. As for other nanomotors, the proper functioning of Myo6 relies on precise spatiotemporal control of motor activity via a poorly defined off-state and interactions with partners. Our structural, functional, and cellular studies reveal key features of myosin regulation and indicate that not all partners can activate Myo6. TOM1 and Dab2 cannot bind the off-state, while GIPC1 binds Myo6, releases its auto-inhibition and triggers proximal dimerization. Myo6 partners thus differentially recruit Myo6. We solved a crystal structure of the proximal dimerization domain, and show that its disruption compromises endocytosis in HeLa cells, emphasizing the importance of Myo6 dimerization. Finally, we show that the L926Q deafness mutation disrupts Myo6 auto-inhibition and indirectly impairs proximal dimerization. Our study thus demonstrates the importance of partners in the control of Myo6 auto-inhibition, localization, and activation.

Bridging the Binding Sites 2.0: Photoswitchable Dualsteric Ligands for the Cannabinoid 2 Receptor.

The cannabinoid receptor 2 (CB2R) has high, unexploited therapeutic potential in several central nervous system disorders due to its involvement in neuroinflammatory processes and pathologies like neurodegeneration. Dualsteric/bitopic ligands are currently developed to achieve receptor subtype selectivity and biased signaling. To obtain a molecular tool compound with photoswitchable potential dualsteric properties, we applied two different approaches to link a positive allosteric modulator with an orthosteric agonist via a photochromic unit. We characterized the photophysical properties of all compounds and determined efficacy in internalization, calcium mobilization, and BRET studies. We report the first potentially dualsteric photoswitchable ligand for studying molecular mechanisms of CB2R-associated pathologies. Compound 17-para is a submicromolar "cis-on" agonist with >10-fold higher potency compared to its trans photoisomer and allows high spatiotemporal control of CB2R activation.

Melanocortin-3 receptor expression in AgRP neurons is required for normal activation of the neurons in response to energy deficiency

The melanocortin-3 receptor (MC3R) is a negative regulator of the central melanocortin circuitry via presynaptic expression on agouti-related protein (AgRP) nerve terminals, from where it regulates GABA release onto secondary MC4R-expressing neurons. However, MC3R knockout (KO) mice also exhibit defective behavioral and neuroendocrine responses to fasting. Here, we demonstrate that MC3R KO mice exhibit defective activation of AgRP neurons in response to fasting, cold exposure, or ghrelin while exhibiting normal inhibition of AgRP neurons by sensory detection of food in the ad libitum-fed state. Using a conditional MC3R KO model, we show that the control of AgRP neuron activation by fasting and ghrelin requires the specific presence of MC3R within AgRP neurons. Thus, MC3R is a crucial player in the responsiveness of the AgRP soma to both hormonal and neuronal signals of energy need.

Linking corticospinal tract activation and upper-limb motor control in adults with cerebral palsy.

To quantify the cervicomedullary motor evoked potentials (CMEPs) at the cervical spinal level in adults with cerebral palsy (CP) and determine if altered CMEPs are linked with upper-extremity motor function in this population. This cross-sectional study consisted of a cohort of adults with CP (n = 15; mean age = 33 years 5 months [SD = 11 years 8 months]); Manual Ability Classification System levels I-IV) and neurotypical controls (n = 18; mean age = 30 years 10 months [SD = 10 years 4 months]), who were recruited to participate at an academic medical center. Adults with CP and typical adults (controls) were stimulated at the cervicomedullary junction to assess CMEPs at the cervical spinal cord level. Upper-extremity motor function was quantified using the Box and Blocks and Purdue Pegboard tests, self-reported upper-extremity function (UEF), and assessments of selective motor control. At higher stimulation levels, the contralateral CMEP responses of adults with CP were different from typical adults (p = 0.032). Reduced CMEP was correlated with reduced upper-limb function, including worse performance on the Box and Blocks (rho = 0.625, p = 0.025) and Purdue Pegboard tests (rho = 0.701, p = 0.010), lower self-reported UEF (rho = 0.761, p = 0.009), and overall selective motor control (rho = 0.731, p = 0.007). Changes in the activation of spinal motoneurons through corticospinal pathways may have an important role in the altered upper-extremity motor function of individuals with CP.

Cu-Based Thermocompression Bonding and Cu/Dielectric Hybrid Bonding for Three-Dimensional Integrated Circuits (3D ICs) Application.

Advanced packaging technology has become more and more important in the semiconductor industry because of the benefits of higher I/O density compared to conventional soldering technology. In advanced packaging technology, copper-copper (Cu-Cu) bonding has become the preferred choice due to its excellent electrical and thermal properties. However, one of the major challenges of Cu-Cu bonding is the high thermal budget of the bonding process caused by Cu oxidation, which can result in wafer warpage and other back-end-of-line process issues in some cases. Thus, for specific applications, reducing the thermal budget and preventing Cu oxidation are important considerations in low-temperature hybrid bonding processes. This paper first reviews the advancements in low-temperature Cu-based bonding technologies for advanced packaging. Various low-temperature Cu-Cu bonding techniques such as surface pretreatment, surface activation, structure modification, and orientation control have been proposed and investigated. To overcome coplanarity issues of Cu pillars and insufficient gaps for filling, low-temperature Cu-Cu bonding used, but it is still challenging in fine-pitch applications. Therefore, low-temperature Cu/SiO2, Cu/SiCN, and Cu/polymer hybrid bonding have been developed for advanced packaging applications. Furthermore, we present a novel hybrid bonding scheme for metal/polymer interfaces that achieves good flatness and an excellent bonding interface without the need for the chemical mechanical polishing (CMP) process.

Dispositional Associations Between Interoceptive Attention Tendencies and Effortful Control: Cross‐sectional Findings from an Online National Survey of Japanese Working Adults

AbstractInteroceptive attention tendencies (IATs) have been theorized to include facets of awareness and evaluative aspects for skillfully attending toward one's bodily sensations in a regulatory manner. However, the relations between IATs and factors for the trait‐like control of behavioral effort are unknown. Here, we tested associations between IATs measured via the Multidimensional Assessment of Interoceptive Awareness (MAIA) and control‐related factors from the Effortful Control Scale (ECS) for adults in a nationally representative online survey of 500 Japanese working adults (analytic sample, N = 463; 274 females, Mage = 46.63 years, SD = 11.58 years). The results of the confirmatory factor analysis for the MAIA showed acceptable model fit for the six‐factor model similar to previous studies with Japanese respondents. Adjusting for the influence of age and gender, partial correlations indicated that the evaluative dimensions of the MAIA were positively correlated with the Inhibitory Control, Activation Control, and Attentional Control factors of the ECS (Pearson's partial rs range .14 to .25, ps < .01). Exploratory multiple regression analysis indicated that the Attention Regulation factor of the MAIA was a statistically significant predictor of effortful control modeled as total score. Taken together, the results were theoretically consistent with previous studies investigating relations with trait‐like factors of personality and mental health indicators for full‐time workers in Japan. Relative to the constructs of awareness, our empirical correlations provide specificity for the construct validity of IATs with trait indicators of effortful control and implications for implementation research.

SPATIO-TEMPORAL PATTERNS OF CORTICAL-MUSCULAR INTERACTION DURING LOCOMOTION

The paper considers the synergetic effects manifested at the cortical and muscular levels during locomotor activity showed in conditions of horizontal hanging of the lower extremities. The analysis of the synergies’ spatio-temporal structure was carried out using the data matrix factorization methods. It was found out the control of the movements’ structure is mainly realized through the three muscle synergies. The activity synchronization of the motor, associative, visual and sensorimotor regions of the cortex bilateral part is due to the specifics of performing locomotion in conditions of gravitational unloading and the associated features of receptor signaling. The identified components indicating synchronization of different areas of the right and left cortex may reflect the control processes associated with the control of alternate activation of the flexor and extensor muscles of the contralateral limb during locomotion. The data on the cortical activity spatial-temporal structuring indicate the separate management of muscle synergies through synchronization of cortical commands and the temporary organization of muscle synergies in the frequency ranges 0.30 to 8.00 Hz. Such patterns may reflect the activity of the rhythm-generating mechanism involved in the management of cyclic locomotor activity.