Regular Functions Research Articles

The Role and Interactive Mechanism of Endoplasmic Reticulum Stress and Ferroptosis in Musculoskeletal Disorders

Endoplasmic reticulum (ER) stress is a cellular phenomenon that arises in response to the accumulation of misfolded proteins within the ER. This process triggers the activation of a signalling pathway known as the unfolded protein response (UPR), which aims to restore ER homeostasis by reducing protein synthesis, increasing protein degradation, and promoting proper protein folding. However, excessive ER stress can perturb regular cellular function and contribute to the development of diverse pathological conditions. As is well known, ferroptosis is a kind of programmed cell death characterized by the accumulation of lipid peroxides and iron-dependent reactive oxygen species (ROS), resulting in oxidative harm to cellular structures. In recent years, there has been increasing evidence indicating that ferroptosis occurs in musculoskeletal disorders (MSDs), with emerging recognition of the complex relationship between ER stress and ferroptosis. This review presents a summary of ER stress and the ferroptosis pathway. Most importantly, it delves into the significance of ER stress in the ferroptosis process within diverse skeletal or muscle cell types. Furthermore, we highlight the potential benefits of targeting the correlation between ER stress and ferroptosis in treating degenerative MSDs.

ND15, subunit of the electron transport chain protein-complex I, age-dependently worsens cardiac performance in Drosophila melanogaster

Abstract Introduction In the natural aging process of the heart, aside others, mitochondrial dysfunction is an essential driver for the development of reduced cardiac performance. Previous analysis of protein expression levels in cardiomyocytes of aged mice and have found aberrancies in subunits of the mitochondrial Complexes I – IV of the electron transport chain. Especially, the complex I subunit ND15 was highly downregulated. To elucidate the functional effects of this gene on the cardiac performance, we generated cardiomyocyte specific ND15 knock-downs in Drosophila melanogaster. Methods We generated Drosophila with heart-specific (+/+; Hand4.2-GAL4/UAS-ND15; tdtK/+) (ND15-KD)knockdown of ND15 using the UAS/GAL4 system. The flies' cardiomyocytes endogenously express tdTomato, facilitating fluorescence-based live imaging of the heart by high-resolution video fluorescence microscopy. The recorded data was processed using a R-Script, resulting in Results We compared wild type (WT) flies to ND15-KD flies at age 3 weeks(young) and 7 weeks(old). Knockdown of ND15 resulted in impaired cardiac function. Most parameters deteriorated in aged flies in comparison to young flies. The heart frequency was significantly reduced (WT:6 beats/s – KD:4 beats/s – p<0.0001) in the 7 weeks old group, end-diastolic diameter of the heart tube increased significantly in 3 weeks old ND15KD flies compared to controls(WT:65µm – KD:74µm p<0,0001), resulting in a dilated heart tube Interestingly enough, this dilation in ND15-KD disappeared in 7 weeks old flies. The fractional shortening was significantly decreased in young(WT:33,5% - KD:30% p<0,01) and deteriorated in old flies (WT:35% - KD:22% p<0,0001), indicating a reduced contraction capability. For both 3 weeks and 7 weeks old groups, the heart-rate adjusted interbeat interval variance (WT:22% -KD: 40% p<0,0001) as well as the time of no cardiac action (WT: 22% - KD: 35% p<0,0001) increased and showed significant irregularities. The duration of systole and diastole combined also exhibited arrhythmic patterns (WT:15% - KD:20.5% p<0,0001). A general arrhythmia index (AI) increased significantly (WT: 0.25 – KD:0.5 p<0,0001) These arrhythmia parameters emphasize the arrhythmogenic potential of the ND15-knockdown. The relative relaxation capabilities drastically worsened with age, displaying a diastolic dysfunction in the 7 weeks old group. At half-time relaxation, the WT was at 60% relaxation, ND15KD at 46%). Conclusion This study demonstrates that heart-specific deletion of ND15 results in a marked impairment of systolic and diastolic cardiac function in Drosophila accompanied by pro-arrhythmogenic actions. We could identify ND15 as a new mitochondrial molecular target for the maintenance of regular cardiac function and rhythmicity, especially with increasing age. Further mechanistic studies and translation to mammalian organisms are ongoing.

ERFLSTM: Enhanced regularization function in LSTM to assess feature importance

ERFLSTM: Enhanced regularization function in LSTM to assess feature importance

ExpAvatar: High-Fidelity Avatar Generation of Unseen Expressions with 3D Face Priors

The reconstruction of dynamic head avatars has gained increasing significance, giving rise to various downstream applications such as visual dubbing and digital human creation. Despite recent advancements, generating novel, unseen expressions for a given identity remains challenging in concurrently achieving 1) accurate expression and consistent appearance and 2) high-quality and realistic faces. This paper introduces ExpAvatar, a novel approach crafted to address these challenges. ExpAvatar elaborately leverages the appearance consistency capabilities inherent in 3DMMs-based models along with the robust generalization ability of DDPMs-based models to alleviate appearance drift issues and enhance the generation of unseen expressions. Specifically, ExpAvatar introduces a Face Priors-conditioned Diffusion model (FPDiff) to inject 3D face priors into generation models through fine-tuning. Furthermore, a Face Priors-conditioned Catalyst (FPCatalyst) is employed to enhance the inference efficiency and generation quality. Moreover, we propose a unique confidence-based regularizer function to mitigate the effect of imperfect face-tracking estimates, thereby improving the quality of dynamic neural head avatars. Experimental results demonstrate that ExpAvatar surpasses current state-of-the-art solutions in generating unseen expressions, marking an advancement in the realm of dynamic head avatar synthesis. Code: https://github.com/yuangan/ExpAvatar .

Fractional integration of summable functions: Maz'ya's~$\Phi$-inequalities

We study the inequalities of the type $|\int_{\mathbb{R}^d} \Phi(K*f)| \lesssim \|f\|_{L_1(\mathbb{R}^d)}^p$, where the kernel $K$ is homogeneous of order $\alpha - d$ and possibly vector-valued, the function $\Phi$ is positively $p$-homogeneous, and $p = d/(d-\alpha)$. Under mild regularity assumptions on $K$ and $\Phi$, we find necessary and sufficient conditions on these functions under which the inequality holds true with a uniform constant for all sufficiently regular functions $f$.

Overexpressing Carbonic Anhydrase Transgenic Rice Plants Maintain the Regular Soil Functions and Microbial Activities of Soil

Background: Genetically modified (GM) crops are focused on establishing desirable traits to support the food demand of increasing populations. The effect of transgenic plants on soil diversity has been highlighted by a lot of researchers. Some of them showed the negative effect of transgenic crop on soil microbes and the food chain. So there is an urgent need to develop transgenic plants with no harmful effects on environmental health. Methods: We have examined the effects salt tolerant carbonic anhydrase overexpressing transgenic rice plants on the physiology of rhizospheric microbes and their enzymatic activities. In the present study, we have used pot experiments in the greenhouse of Centurion University of Technology and management, Bhubaneswar, Odisha, India. Result: No significant variation in the soil properties viz., pH, Eh, organic C, P, K, N, Ca, Mg, S, Na and Fe+2 were observed. The population of bacteria, fungi and nematodes were remained same in the soil. The enzymatic activities like soil dehydrogenase, nitrate reductase, urease and alkaline phosphatase were not significantly affected. Further, plant growth promotion (PGP) functions such as HCN, siderophore, salicylic acid, GA, IAA, zeatin, were, not influenced considerably. The present study ecologically pertinent of salt tolerant CA transgenic rice to usual functions of the rhizospheric organisms.

Association schemes arising from non-weakly regular bent functions

Association schemes arising from non-weakly regular bent functions

Effects of testosterone and metformin on the GlycanAge index of biological age and the composition of the IgG glycome.

With aging, the body's ability to maintain regular functions declines, increasing susceptibility to age-related diseases. Therapeutic interventions targeting the underlying biological changes of aging hold promise for preventing or delaying multiple age-related diseases. Metformin, a drug commonly used for diabetes treatment, has emerged as a potential gerotherapeutic agent due to its established safety record and preclinical and clinical data on its anti-aging effects. Glycosylation, one of the most common and complex co- and post-translational protein modifications, plays a crucial role in regulating protein function and has been linked to aging and various diseases. Changes in immunoglobulin G (IgG) glycosylation patterns have been observed with age, and these alterations may serve as valuable biomarkers for disease predisposition, diagnosis, treatment monitoring, and overall health assessment. In this study, we analyzed the IgG glycosylation patterns of white men from Europe, aged 29-45years, under treatment with metformin, testosterone, metformin plus testosterone, and placebo (trial registration number NCT02514629, 2013/07/04), and investigated the longitudinal changes in glycosylation over time. We observed statistically significant differences in the IgG glycome composition between participants on testosterone therapy and placebo, with decreased agalactosylation and increased galactosylation and sialylation. However, metformin therapy did not result in statistically significant changes in glycosylation patterns. These findings contribute to our understanding of the impact of therapeutic interventions on IgG glycosylation and confirm the value of IgG glycosylation as a significant biomarker, capable of assessing biological age using the GlycanAge index and providing insight into overall health compared to chronological age.

$$\ell $$-Adic properties and congruences of $$\ell $$-regular partition functions

$$\ell $$-Adic properties and congruences of $$\ell $$-regular partition functions

Better than the Total Variation Regularization

The total variation (TV) regularization is popular in iterative image reconstruction when the piecewise-constant nature of the image is encouraged. As a matter of fact, the TV regularization is not strong enough to enforce the piecewise- constant appearance. This paper suggests a different regularization function that is able to discourage some smooth transitions in the image and to encourage the piecewise-constant behavior. This new regularization function involves a Gaussian function. We use the limited-angle tomography problem to illustrate the effectiveness of this new regularization function. The limited-angle tomography situation considered in this paper uses a scanning angular range of 40°. For two-dimensional parallel-beam imaging, the required angular range is supposed to be 180°.

Physics-Inspired Evolutionary Machine Learning Method: From the Schrödinger Equation to an Orbital-Free-DFT Kinetic Energy Functional.

We introduce a machine learning (ML)-supervised model function (which is in fact a functional rather than a regular function) that is inspired by the variational principle of physics. This ML hypothesis evolutionary method, termed ML-Ω, allows us to go from data to differential equation(s) underlying the physical (chemical, engineering, etc.) phenomena from which the data are derived from. The fundamental equations of physics can be derived from this ML-Ω evolutionary method when the proper training data is used. By training the ML-Ω model function with only three hydrogen-like atom energies, the method can find Schrödinger's exact functional and, from it, Schrödinger's fundamental equation. Then, in the field of density functional theory (DFT), when the model function is trained with the energies from the known Thomas-Fermi (TF) formula , it correctly finds the exact TF functional. Finally, the method is applied to find a local orbital-free (OF) functional expression of the independent electron kinetic energy functional Ts based on the γTFλvW model. By considering the theoretical energies of only five atoms (He, Be, Ne, Mg, and Ar) as the training set, the evolutionary ML-Ω method finds an ML-Ω-OF-DFT local Ts functional (γTFλvW(0.964,1/4)) that outperforms all the OF-DFT functionals of a representative group. Moreover, our ML-Ω-OF functional overcomes the difficulty of LDA's and some local generalized gradient approximation (GGA)-DFT's functionals to describe the stretched bond region at the correct spin configuration of diatomic molecules. Nonsmooth and nonclosed form functionals can be considered in the ML-Ω model function and still be effectively trained. Although our evolutionary ML-Ω model function can work without an explicit prior-form functional, by using the techniques of symbolic regression, in this work, we exploit prior-form functional expressions to make the training process simpler and faster. The ML-Ω method can be considered at the intersection of ML and the natural sciences.

Thermal Buckling and Postbuckling Analysis of Cracked FG-GPL RC Plates Using a Phase-Field Crack Model

A phase-field crack model is developed for numerical analysis of thermal buckling and postbuckling behavior of a functionally graded (FG) graphene platelet-reinforced composite (FG-GPLRC) plate with a central crack. The inclined central crack is represented according to a stable, effective phase-field formulation (PFF) by introducing a virtual crack rotation. The problem is formulated using first-order shear deformation theory (SDT) incorporated with von Kármán geometric nonlinearity. And it is approximated by combining regular Laplace interpolation functions and crack-tip singular functions in the framework of the 2D extended natural element method (XNEM). Troublesome shear locking is suppressed by applying the concept of the MITC (mixed-interpolated tensorial components)3+ shell element to the present numerical method. The results demonstrate the effectiveness of this method in accurately predicting the critical buckling temperature rise (CBTR) and the thermal postbuckling path. In addition, the parametric results reveal that the CBTR and postbuckling path of the FG-GPLRC plate are distinct from those of the FG carbon nanotube-reinforced composite (FG-CNTRC) plate and remarkably affected by the parameters associated with the crack and graphene platelet (GPL).

Apple varieties and growth prediction with time series classification based on deep learning to impact the harvesting decisions

Apples are among the most popular fruits globally due to their health and nutritional benefits for humans. Artificial intelligence in agriculture has advanced, but vision, which improves machine efficiency, speed, and production, still needs to be improved. Managing apple development from planting to harvest affects productivity, quality, and economics. In this study, by establishing a vision system platform with a range of camera types that conforms with orchard standard specifications for data gathering, this work provides two new apple collections: Orchard Fuji Growth Stages (OFGS) and Orchard Apple Varieties (OAV), with preliminary benchmark assessments. Secondly, this research proposes the orchard apple vision transformer method (POA-VT), incorporating novel regularization techniques (CRT) that assist us in boosting efficiency and optimizing the loss functions. The highest accuracy scores are 91.56 % for OFGS and 94.20 % for OAV. Thirdly, an ablation study will be conducted to demonstrate the importance of CRT to the proposed method. Fourthly, the CRT outperforms the baselines by comparing it with the standard regularization functions. Finally, time series analyses predict the ‘Fuji’ growth stage, with the outstanding training and validation RMSE being 19.29 and 19.26, respectively. The proposed method offers high efficiency via multiple tasks and improves the automation of apple systems. It is highly flexible in handling various tasks related to apple fruits. Furthermore, it can integrate with real-time systems, such as UAVs and sorting systems. This research benefits the growth of apple’s robotic vision, development policies, time-sensitive harvesting schedules, and decision-making.

Prevalence of Hypothyroidism in Children with Transfusion Dependent Thalassemia Patient Attending in A Tertiary Care Hospital of Bangladesh

Background: Blood transfusions and iron chelation are standard treatments for β-thalassemia major and Hb E-Beta-Thalassemia. However, repeated transfusions raise body iron levels, leading to secondary hemosiderosis and complications in the heart, endocrine system, and liver. Thyroid dysfunction results from gland infiltration, chronic hypoxia, free radical damage, and iron overload. This study aimed to find out the prevalence of hypothyroidism in transfusion-dependent thalassemic children attending Bangladesh Shishu Hospital & Institute. Methods: A descriptive cross-sectional study was conducted at the Thalassemia Centre, Department of Hematology and Oncology, Bangladesh Shishu Hospital & Institute, from December 2019 to November 2020. The study included 140 children with thalassemia, aged 5 to 16 years, who were receiving blood transfusions. Data were collected using a structured questionnaire with participant consent. Statistical analysis was performed using SPSS version 23.0. Results: In this study, hypothyroidism was observed in 26.2% of patients, with 23.5% having subclinical and 2.9% overt hypothyroidism. In most of the patients (n=85), aged 11-16 years, 58.3% had normal thyroid function, 36.5% had subclinical, and 4.7% had overt hypothyroidism, which was statistically significant (p<0.05). Of the 91 patients with hemoglobin levels below 11.5 g/dL, 85.7% had normal thyroid function, 13.2% had subclinical hypothyroidism, and 1.1% had overt hypothyroidism, also significant (p<0.05). In the group with ferritin levels of 1200-2000 ng/mL, 78.1% had normal thyroid function, 18.8% had subclinical hypothyroidism, and 3.1% had overt hypothyroidism, which was not statistically significant (p>0.05). Conclusion: Subclinical hypothyroidism is commonly seen in thalassemia patients aged 5 to 16 years who undergo regular blood transfusions. Regular physical exams and thyroid function assessments are crucial to detect overt hypothyroidism early. Timely hormone replacement can

Weighted Contrastive Prototype Network for Few-Shot Hyperspectral Image Classification with Noisy Labels

Few-shot hyperspectral image classification aims to develop the ability of classifying image pixels by using relatively few labeled pixels per class. However, due to the inaccuracy of the localization system and the bias of the ground survey, the potential noisy labels in the training data pose a very significant challenge to few-shot hyperspectral image classification. To solve this problem, this paper proposes a weighted contrastive prototype network (WCPN) for few-shot hyperspectral image classification with noisy labels. WCPN first utilizes a similarity metric to generate the weights of the samples from the same classes, and applies them to calibrate the class prototypes of support and query sets. Then the weighted prototype network will minimize the distance between features and prototypes to train the network. WCPN also incorporates a weighted contrastive regularization function that uses the sample weights as gates to filter the fake positive samples whose labels are incorrect to further improve the discriminative power of the prototypes. We conduct experiments on multiple hyperspectral image datasets with artificially generated noisy labels, and the results show that the WCPN has excellent performance that can sufficiently mitigate the impact of noisy labels.

Differential geometry and general relativity with algebraifolds

It is often noted that many of the basic concepts of differential geometry, such as the definition of connection, are purely algebraic in nature. Here, we review and extend existing work on fully algebraic formulations of differential geometry which eliminate the need for an underlying manifold. While the literature contains various independent approaches to this, we focus on one particular approach that we argue to be the most natural one based on the definition of algebraifold, by which we mean a commutative algebra A for which the module of derivations of A is finitely generated projective. Over R as the base ring, this class of algebras includes the algebra C∞(M) of smooth functions on a manifold M, and similarly for analytic functions. An importantly different example is the Colombeau algebra of generalized functions on M, which makes distributional differential geometry an instance of our formalism. Another instance is a fibred version of smooth differential geometry, since any smooth submersion M→N makes C∞(M) into an algebraifold with C∞(N) as the base ring. Over any field k of characteristic zero, examples include the algebra of regular functions on a smooth affine variety as well as any function field.Our development of differential geometry in terms of algebraifolds comprises tensors, connections, curvature, geodesics and we briefly consider general relativity.

Structure‐preserving interpolation of quadratic‐bilinear systems via regular multivariate transfer functions

Structure‐preserving interpolation of quadratic‐bilinear systems via regular multivariate transfer functions

Some operators of fractional calculus and their applications regarding various complex functions analytic in certain domains

Abstract. In this academic research note, some familiar operators prearranged by fractional-order calculus will first be introduced and various characteristic properties of those operators will next be propounded. Through the instrumentality of various earlier results associating with both those operators and some complex- exponential forms, and also in the light of certain special information in [1], [20], [17] and [38], an extensive result together with a variety of its implications consisting of several exponential type inequalities will then be determined. A number of its possible implications will extra be pointed out. Mathematics Subject Classification (2010): 26A33, 30A10, 34A40, 35A30, 41A58, 30C45, 30C55, 30C80, 33D15, 26E05, 33E20. Keywords: Complex plane, domains, regular functions, complex exponential, series expansions, fractional calculus, operators of fractional calculus, exponential type inequalities, differential inequalities.

Characterization of Shy1, the Schizosaccharomyces pombe homolog of human SURF1

Cytochrome c oxidase (complex IV) is the terminal enzyme in the mitochondrial respiratory chain. As a rare neurometabolic disorder caused by mutations in the human complex IV assembly factor SURF1, Leigh Syndrome (LS) is associated with complex IV deficiency. In this study, we comprehensively characterized Schizosaccharomyces pombe Shy1, the homolog of human SURF1. Bioinformatics analysis revealed that Shy1 contains a conserved SURF1 domain that links to the biogenesis of complex IV and shares high structural similarity with its homologs in Saccharomyces cerevisiae and humans. Our study showed that Shy1 is required for the expression of mtDNA-encoded genes and physically interacts with structural subunits and assembly factors of complex IV. Interestingly, Rip1, the subunit of ubiquinone-cytochrome c oxidoreductase or cytochrome bc1 complex (complex III), can also co-immunoprecipitate with Shy1, suggesting Shy1 may be involved in the assembly of the mitochondrial respiratory chain supercomplexes. This conclusion is further corroborated by our BN-PAGE analysis. Unlike its homologs, deletion of shy1 does not critically disrupt respiratory chain assembly, indicating the presence of the compensatory mechanism(s) within S. pombe that ensure mitochondrial functionality. Collectively, our investigation elucidates that Shy1 plays a pivotal role in the sustainability of the regular function of mitochondria by participating in the assembly of complex IV in S. pombe.

Dynamics of Neurogenic Signals as Biological Switchers of Brain Plasticity.

The discovery of adult neurogenesis in the middle of the past century is considered one of the most important breakthroughs in neuroscience. Despite its controversial nature, this discovery shaped our concept of neural plasticity, revolutionizing the way we look at our brains. In fact, after the discovery of adult neurogenesis, we started to consider the brain as something even more dynamic and highly adaptable. In neurogenic niches, adult neurogenesis is supported by neural stem cells (NSCs). These cells possess a unique set of characteristics such as being quiescent for long periods while actively sensing and reacting to their surroundings to influence a multitude of processes, including the generation of new neurons and glial cells. Therefore, NSCs can be viewed as sentinels to our brain's homeostasis, being able to replace damaged cells and simultaneously secrete numerous factors that restore regular brain function. In addition, it is becoming increasingly evident that NSCs play a central role in memory formation and consolidation. In this review, we will dissect how NSCs influence their surroundings through paracrine and autocrine types of action. We will also depict the mechanism of action of each factor. Finally, we will describe how NSCs integrate different and often opposing signals to guide their fate.