Search Results (32)

It is well known that mean elements obtained by canonical perturbation theory only agree partially with the average dynamics of the osculating orbit. While this fact does not necessarily compromise the accuracy of corresponding perturbation solutions, the loose use of the terminology “mean elements” in artificial satellite theory may obscure the understanding of the variety of available solutions in the literature, and thus make the implementation of additional patches to increase their performance ambiguous. We resort to noncanonical perturbation methods, and, for the main problem of artificial satellite theory (the $J_2$-problem), compute the purely periodic, noncanonical, mean-to-osculating transformation that yields the exact separation between short- and long-period variations up to the second order of the zonal harmonic of the second degree. To our knowledge this transformation is new and was long-awaited by software developers in order to improve operational orbit propagation tools based on semianalytical integration. It is also shown that this kind of noncanonical solution confines the long-period oscillations of the semimajor axis in the mean variation equations. Full article

The tripartite-motif protein 56 (TRIM56) is a RING-type E3 ubiquitin ligase whose functions were recently beginning to be unveiled. While the physiological role(s) of TRIM56 remains unclear, emerging evidence suggests this protein participates in host innate defense mechanisms that guard against viral infections. Interestingly, TRIM56 has been shown to pose a barrier to viruses of distinct families by utilizing its different domains. Apart from exerting direct, restrictive effects on viral propagation, TRIM56 is implicated in regulating innate immune signaling pathways that orchestrate type I interferon response or autophagy, through which it indirectly impacts viral fitness. Remarkably, depending on viral infection settings, TRIM56 either operates in a canonical, E3 ligase-dependent fashion or adopts an enzymatically independent, non-canonical mechanism to bolster innate immune signaling. Moreover, the recent revelation that TRIM56 is an RNA-binding protein sheds new light on its antiviral mechanisms against RNA viruses. This review summarizes recent advances in the emerging roles of TRIM56 in innate antiviral immunity. We focus on its direct virus-restricting effects and its influence on innate immune signaling through two critical pathways: the endolysosome-initiated, double-stranded RNA-sensing TLR3-TRIF pathway and the cytosolic DNA-sensing, cGAS-STING pathway. We discuss the underpinning mechanisms of action and the questions that remain. Further studies understanding the complexity of TRIM56 involvement in innate immunity will add to critical knowledge that could be leveraged for developing antiviral therapeutics. Full article

Endogenous DNA damage occurs throughout the cell cycle, with cells responding differently at various stages. The base excision repair (BER) pathway predominantly repairs damaged bases in the genome. While extensively studied in interphase cells, it is unknown if BER operates in mitosis and how apurinic/apyrimidinic (AP) sites, intermediates in the BER pathway that inhibit transcriptional elongation, are processed for post-mitotic gene reactivation. In this study, using an alkaline comet assay, we demonstrate that BER is inefficient in mitosis and that AP endonuclease 1 (APE1), a key BER enzyme, is required for the repair of damage post-mitosis. We previously demonstrated that APE1 is acetylated (AcAPE1) in the chromatin. Using high-resolution microscopy, we show that AcAPE1 remains associated with specific regions in the condensed chromatin in each of the phases of mitosis. This association presumably occurs via the binding of APE1 to the G-quadruplex structure, a non-canonical DNA structure predominantly present in the transcribed gene regions. Additionally, using a nascent RNA detection strategy, we demonstrate that the knockdown of APE1 delayed the rapid post-mitotic transcriptional reactivation of genes. Our findings highlight the functional importance of APE1 in the mitotic chromosomes to facilitate faster repair of endogenous damage and rapid post-mitotic gene reactivation in daughter cells. Full article

The purpose of this paper is to add some new asymptotic and oscillatory results for third-order neutral delay differential equations with noncanonical operators. Without assuming any extra conditions, by using the canonical transform technique, the studied equation is changed to a canonical type equation, and this reduces the number of classes of nonoscillatory solutions into two instead of four. Then, we obtain Myshkis type sufficient conditions for the nonexistence of Kneser type solutions for the studied equation. Finally, employing these newly obtained criteria, we provide conditions for the oscillation of all solutions of the studied equation. Examples are presented to illustrate the importance and the significance of the main results. Full article

The virus–host relationship is indispensable for executing successful viral infection. The pathogenesis of HIV is determined by an intricate interaction between the host and the virus for the regulation of HIV infection, thereby influencing various aspects, including the regulation of signaling pathways. High mutation rates and population heterogeneity characterize HIV with consequences for viral pathogenesis and the potential to escape the immune system and anti-viral inhibitors used in therapy. The origin of the high mutation rates exhibited by HIV may be attributed to a limited template-copied fidelity that likely operates in the cytoplasm. HIV-1 infection induces upregulation and activation of tumor suppressor p53 protein in the early stages of HIV-1 infection. p53 plays a multifaceted role in the context of HIV infection, thereby affecting viral replication. p53 is involved in maintaining genetic integrity, actively participating in various DNA repair processes through its various biochemical activities and via its ability to interact with components of the repair machinery. This report focuses on the impact of the p53 protein on the HIV-1 reverse transcription process while incorporating various incorrect and non-canonical nucleotides. The presence of functional host-coded p53 protein with proofreading–repair activities in the cytoplasm may lead to various biological outcomes. Full article

To describe the hysteresis nonlinearities in smart actuators, numerous models have been presented in the literature, among which the Preisach operator is the most effective due to its capability to capture multi-loop or sophisticated hysteresis curves. When such an operator is coupled with uncertain nonlinear dynamics, especially in noncanonical form, it is a challenging problem to develop techniques to cancel out the hysteresis effects and, at the same time, achieve asymptotic tracking performance. To address this problem, in this paper, we investigate the problem of iterative inverse-based adaptive control for uncertain noncanonical nonlinear systems with unknown input Preisach hysteresis, and a new adaptive version of the closest-match algorithm is proposed to compensate for the Preisach hysteresis. With our scheme, the stability and convergence of the closed-loop system can be established. The effectiveness of the proposed control scheme is illustrated through simulation and experimental results. Full article

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease due to early metastatic spread, late diagnosis and the lack of efficient therapies. A major driver of cancer progression and hurdle to successful treatment is transforming growth factor (TGF)-β. Recent data from pancreatic cancer mouse models showed that transcriptionally active p73 (TAp73), a p53 family member, inhibits tumor progression through promoting tumor suppressive canonical TGF-β/Smad signaling, while preventing non-canonical TGF-β signaling through extracellular signal-regulated kinases (ERK)1/2. Here, we studied whether this mechanism also operates in human PDAC. Using the PDAC-derived tumor cell lines PANC-1, HPAFII and L3.6pl, we showed that TAp73 induces the expression of the epithelial marker and invasion suppressor E-cadherin and the common-mediator Smad, SMAD4, while at the same time suppressing expression of the EMT master regulator SNAIL and basal and TGF-β1-induced activation of ERK1 and ERK2. Using dominant-negative and RNA interference-based inhibition of SMAD4 function, we went on to show that inhibition of ERK activation by TAp73 is mediated through SMAD4. Intriguingly, both SMAD4 and the α isoform of TAp73—but not the β isoform—interfered with cell migration, as shown by xCELLigence technology. Our findings highlighted the role of TAp73-SMAD4 signaling in tumor suppression of human PDAC and identified direct inhibition of basal and TGF-β-stimulated pro-invasive ERK activation as an underlying mechanism. Full article

In this paper, the tracking control problem of a class of fuzzy approximation-based noncanonical nonlinear systems with hysteresis inputs is investigated, where the fuzzy weight matrix is not available for measurement, and the hysteresis nonlinearities are modeled by the Prandtl–Ishlinskii operator. Due to the coupling effects, the plant input containing hysteresis is unknown. To solve the problem, two adaptive control schemes are developed. The first is a Lyapunov-based scheme, and the second is a gradient-based scheme. For convenience, only the relative-degree-one case is taken into account in design and analysis. With the proposed schemes, it can be proved that all signals in the closed-loop system are bounded, and the tracking error converges to a small region around zero. Simulation results show that the maximum steady-state error converges to $[-0.0131,0.0183]\mathsf{\mu }\mathrm{m}$ and $[-0.0139,0.0161]\mathsf{\mu }\mathrm{m}$ with two control schemes, which confirms the obtained results. Full article

The study of the symmetric properties of differential equations is essential for identifying effective methods for solving them. In this paper, we examine the oscillatory behavior of solutions of Emden–Fowler-type mixed non-linear neutral differential equations with both canonical and non-canonical operators. By utilizing integral conditions and the integral averaging method, we present new sufficient conditions to ensure that all solutions are oscillatory. Our results enhance and extend previous findings in the literature and are illustrated with suitable examples to demonstrate their effectiveness. Full article

The present article aims to study the oscillatory properties of a class of second-order dynamic equations on time scales. We consider during this study the noncanonical case, which did not receive much attention compared to the canonical dynamic equations. The approach adopted depends on converting the noncanonical equation to a corresponding canonical equation. By using this transformation and based on several techniques, we create new, more effective, and sharp oscillation criteria. Finally, we explain the effectiveness and importance of the results by applying them to some special cases of the studied equation. Full article

The immediately preverbal position has been argued to be the default focus position in Turkish. In absence of any overt focus markers, the constituent in this position is considered to carry sentential stress and neutral information for canonical word-order sentences and focus is projected to the whole sentence in the form of broad focus. In non-canonical word-order sentences, the immediately preverbal constituent is presumed to carry focal stress and the focused constituent would receive narrow focus. This paper tested this claim experimentally. The paper also investigated if there were any differences in the cognitive operations associated with processing and revising focus in canonical and non-canonical sentences. There were a sentence completion task and an eye-tracking experiment. The sentence completion data and the eye-tracking data supported the theoretical predictions: the immediately preverbal position was associated with default focus in Turkish when no pitch accentuation or other focus markers were available. The eye-tracking data further showed that changes to word-order were perceived as cues for broad versus narrow focus marking. The participants’ processing of and revision from narrow focus were costlier than processing broad focus and assigning narrow focus for the first time. We argue, in line with previous research, that this may be due to deeper encoding of focused information in memory or heavier memory load resulting from keeping a set of alternatives of the focused constituent when it has contrastive meaning. Full article

One of the most abundant non-canonical bases widely occurring on various RNA molecules is 5-methyluridine (m5U). Recent studies have revealed its influences on the development of breast cancer, systemic lupus erythematosus, and the regulation of stress responses. The accurate identification of m⁵U sites is crucial for understanding their biological functions. We propose RNADSN, the first transfer learning deep neural network that learns common features between tRNA m⁵U and mRNA m⁵U to enhance the prediction of mRNA m⁵U. Without seeing the experimentally detected mRNA m⁵U sites, RNADSN has already outperformed the state-of-the-art method, m5UPred. Using mRNA m⁵U classification as an additional layer of supervision, our model achieved another distinct improvement and presented an average area under the receiver operating characteristic curve (AUC) of 0.9422 and an average precision (AP) of 0.7855. The robust performance of RNADSN was also verified by cross-technical and cross-cellular validation. The interpretation of RNADSN also revealed the sequence motif of common features. Therefore, RNADSN should be a useful tool for studying m⁵U modification. Full article

Dosage compensation equalizes gene expression in a single male X chromosome with that in the pairs of autosomes and female X chromosomes. In the fruit fly Drosophila, canonical dosage compensation is implemented by the male-specific lethal (MSL) complex functioning in all male somatic cells. This complex contains acetyl transferase males absent on the first (MOF), which performs H4K16 hyperacetylation specifically in the male X chromosome, thus facilitating transcription of the X-linked genes. However, accumulating evidence points to an existence of additional, non-canonical dosage compensation mechanisms operating in somatic and germline cells. In this review, we discuss current advances in the understanding of both canonical and non-canonical mechanisms of dosage compensation in Drosophila. Full article

G-quadruplexes (G4s) are a unique class of noncanonical DNAs that play a key role in cellular processes and neoplastic transformation. Herein, we focused on the promoter region of human TERT oncogene, whose product is responsible for the immortality of cancer cells. It has been shown by chemical probing and spectroscopic methods that synthetic 96-nt DNAs modeling the wild-type G-rich strand of the hTERT promoter and its variants with G>A point substitutions corresponding to somatic driver mutations fold into three stacked parallel G4s with sites of local G4 destabilization caused by G>A substitutions in the G4 motif. These models were used to elucidate how the hTERT multiG4 affects the binding affinity and functional responses of two key proteins, MutS and MutL, involved in the initial stage of DNA mismatch repair (MMR) in Escherichiacoli and Neisseriagonorrhoeae with different MMR mechanisms. We have shown for the first time that (i) point substitutions do not affect the effective binding of these proteins to the hTERT G4 structure, and (ii) the endonuclease activity of MutL from N. gonorrhoeae is significantly suppressed by the stable G4 scaffold. It is likely that some of the genomic instability associated with G4 may be related to the blockage of human intrinsic methyl-independent MMR attempting to operate near G4 structures. Full article

The study of the oscillatory behavior of solutions to second order nonlinear differential equations is motivated by their numerous applications in the natural sciences and engineering. In the presented research, some new oscillation criteria for a class of damped second order neutral differential equations with noncanonical operators are established. The results extend and improve on those reported in the literature. Moreover, some examples are provided to show the significance of the results. Full article