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Insulin-mechanistic target of rapamycin (mTOR) signaling drives anabolic growth during organismal development; its late-life dysregulation contributes to aging and limits lifespans. Age-related regulatory mechanisms and functional consequences of insulin-mTOR remain incompletely understood. Here, we identify LPD-3 as a megaprotein that orchestrates the tempo of insulin-mTOR signaling during C. elegans aging. We find that an agonist insulin, INS-7, is drastically overproduced from early life and shortens lifespan in lpd-3 mutants. LPD-3 forms a bridge-like tunnel megaprotein to facilitate non-vesicular cellular lipid trafficking. Lipidomic profiling reveals increased hexaceramide species in lpd-3 mutants, accompanied by up-regulation of hexaceramide biosynthetic enzymes, including HYL-1. Reducing the abundance of HYL-1, insulin receptor/DAF-2 or mTOR/LET-363, normalizes INS-7 levels and rescues the lifespan of lpd-3 mutants. LPD-3 antagonizes SINH-1, a key mTORC2 component, and decreases expression with age. We propose that LPD-3 acts as a megaprotein brake for organismal aging and that its age-dependent decline restricts lifespan through the sphingolipid-hexaceramide and insulin-mTOR pathways.

Background: Muscle Tension Dysphonia is a relatively new clinical entity that, despite being one of the most frequent causes of functional dysphonia, is little-known by many otorhinolaryngologists. Objective: The objective of the current work is to describe the evolution of Muscle Tension Dysphonia—the concepts and the ways it has been diagnosed and treated—from its first descriptions to our current knowledge. Design: A scoping review was conducted using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. A search of three bibliographic databases was performed to identify original articles on Muscle Tension Dysphonia. Study selection and characterization was conducted by three independent reviewers and was further reviewed by a fourth individual. In case of relocating any of the studies, it was performed by agreement of two reviewers. We excluded articles not written in English or Spanish, letters to the editor, review articles, studies of the pediatric population, articles related to dysphagia, and other publications that were not relevant. Results: The search identified 1144 articles published from 1983 to December 2022. A total of 581 studies were repeated and another 462 were excluded because they were not written in English or Spanish, were not original articles, or were not relevant to the objective of the study. Finally, 101 articles were included in the review. The articles included in the review were divided into three groups considering the objective and conclusions of each study: 21 articles were classified as "Etiology and Physiopathology", 29 articles as "Diagnosis", and 51 articles were included in the "Treatment" group. Conclusions: The concept of Muscle Tension Dysphonia has been developed during the last forty years. For its diagnosis, endoscopic visualization of the larynx is crucial, but must be combined with the patient's clinical history and other methods can also be useful. This entity should be addressed in a multidisciplinary approach, with the active participation of speech therapists. Most therapeutic options include voice education, vocal hygiene, and rehabilitation of the voice. [ABSTRACT FROM AUTHOR]

In recent years, the direction associated with the study of maps from a finite set A to the set of all subsets of the set A, including the empty one, has been intensively developing. Such mappings are called multifunctions on A, as well as hyperfunctions on A, if an empty subset is excluded from the subsets under consideration. It is not difficult to see that the so-called undefined or undefined functions, which are studied in many works, are most directly related to this field of research. The power of the set A is called the rank of multifunction or hyperfunction. Obviously, multifunctions and hyperfunctions generalize well-known functions of k-valued logic, however, it should be noted that the usual superposition of functions of k-valued logic is not suitable for multifunctions and hyperfunctions. Two types of superpositions are most often considered here, one of them leads to sets closed relative to the superposition, which are called multiclones and hyperclones, and for the second type of superposition, closed sets are called ultraclones and partial ultraclones. In this article, the elements of the rank 2 ultraclone lattice are considered. By now, all the maximum and minimum elements of this lattice are known. For example, Panteleev V.I. described all maximal ultraclones in the predicate language, which allowed us to prove the completeness criterion of an arbitrary system of hyperfunctions of rank 2. We managed to prove the completeness criterion in the maximal ultraclone of linear hyperfunctions of rank 2. Thus, all submaximal ultraclones of linear hyperfunctions are described.

Background: Injecting botulinum neurotoxin (BoNT) into the salivary glands is a common treatment for certain diseases. Green tea's active compound, epigallocatechin-3-gallate (EGCG), has been linked to a variety of health benefits, including the reduction of free radicals and inflammation. This study compared the effects of BoNT and BoNT/EGCG on the submandibular salivary glands (SMG) histology and ultrastructure. Methods: Both BoNT and BoNT/EGCG nanoemulsions were injected into the submandibular salivary glands (SMGs) in adult male albino rats, which were then euthanized, and the right SMGs were thoroughly dissected and prepared for histological, immunohistochemical, and transmission electron microscopic analysis. Results: When compared to the BoNT group, the BoNT/EGCG nanoemulsion group significantly improved SMG acinar and ductal cells using both H&E and immunohistochemical stainings. Ultrastructural findings of the BoNT/EGCG nanoemulsion group revealed marked improvement in the SMG structure, almost normal acini, and striated ducts. Conclusion: Salivary gland histological structures are significantly altered after BoNT administration, but the addition of EGCG causes only minor alterations and can be used to treat hyperfunction.

Background: Muscle Tension Dysphonia is a relatively new clinical entity that, despite being one of the most frequent causes of functional dysphonia, is little-known by many otorhinolaryngologists. Objective: The objective of the current work is to describe the evolution of Muscle Tension Dysphonia—the concepts and the ways it has been diagnosed and treated—from its first descriptions to our current knowledge. Design: A scoping review was conducted using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. A search of three bibliographic databases was performed to identify original articles on Muscle Tension Dysphonia. Study selection and characterization was conducted by three independent reviewers and was further reviewed by a fourth individual. In case of relocating any of the studies, it was performed by agreement of two reviewers. We excluded articles not written in English or Spanish, letters to the editor, review articles, studies of the pediatric population, articles related to dysphagia, and other publications that were not relevant. Results: The search identified 1144 articles published from 1983 to December 2022. A total of 581 studies were repeated and another 462 were excluded because they were not written in English or Spanish, were not original articles, or were not relevant to the objective of the study. Finally, 101 articles were included in the review. The articles included in the review were divided into three groups considering the objective and conclusions of each study: 21 articles were classified as “Etiology and Physiopathology”, 29 articles as “Diagnosis”, and 51 articles were included in the “Treatment” group. Conclusions: The concept of Muscle Tension Dysphonia has been developed during the last forty years. For its diagnosis, endoscopic visualization of the larynx is crucial, but must be combined with the patient’s clinical history and other methods can also be useful. This entity should be addressed in a multidisciplinary approach, with the active participation of speech therapists. Most therapeutic options include voice education, vocal hygiene, and rehabilitation of the voice.

In this paper, we reformulate the quintic and sextic equations in the spaces of generalized functions. Using the pullbacks and the heat kernels, we investigate the approximate quintic and sextic mappings in the spaces of Schwartz tempered distributions and Fourier hyperfunctions. [ABSTRACT FROM AUTHOR]

Currently, concern about facial attractiveness is increasing, and this fact has led to orthodontics in adult patients being an increasingly demanded treatment, and with it, multi-disciplinary work. When it is caused by a vertical excess of the maxilla, the ideal solution is orthognathic surgery. However, in borderline cases and when the cause is hyperactivity of the upper lip levator muscle complex, alternative conservative solutions can be considered, such as the application of botulinum toxin A (BTX-A). Botulinum toxin is a protein produced by a bacterium and causes a reduction in the force of muscle contraction. The multi-factorial nature of the smile requires an individualized diagnosis in each patient, since there are multiple ways to treat the gummy smile (orthognathic surgery, gingivoplasty, orthodontic intrusion). In recent years, interest has grown in the simplest techniques that allow the patient to quickly return to their usual routine, such as lip replacement. However, this procedure shows recurrences in the first 6–8 post-operative weeks. The main objective of this systematic review and meta-analysis is to analyze the effectiveness of BTX-A in the treatment of gummy smile in the short term, to study its stability, and to evaluate potential complications. A thorough search of the PubMed, Scopus, Embase, Web of Science, and Cochrane databases and a grey literature search were conducted. The inclusion criteria were studies with a sample size greater than or equal to 10 patients with gingival exposure greater than 2 mm in smile, treated with BTX-A infiltration. Those patients whose exclusive etiology of their gummy smile was related to altered passive eruption, gingival thickening, or overeruption of upper incisors were excluded. In the qualitative analysis, the mean pre-treatment gingival exposure ranged between 3.5 and 7.2 mm, reaching a reduction of up to 6 mm after infiltration with botulinum toxin at 12 weeks. Although multiple muscles are involved in the facial expression, the muscles par excellence selected for blockade with BTX-A were levator labii superioris, levator labii superioris ala nasalis, and zygomaticus minor, infiltrating from 1.25 to 7.5 units per side. In the quantitative analysis, the difference in mean reduction between both groups was −2.51 mm at two weeks and −2.24 mm at three months. The benefit of BTX-A in terms of improvement of gummy smile is demonstrated, as a significant reduction in gummy smile is estimated by BTX-A therapy two weeks after its application. Its results gradually decrease over time, however, they stay satisfactory without returning to their initial values after 12 weeks. [ABSTRACT FROM AUTHOR]

Purpose: To assess the preliminary outcomes of inferior oblique (IO) disinsertion-distal myectomy and tucking combined with superior oblique (SO) full tendon advancement in patients with Knapp II or III superior oblique palsy. Methods: This single-centered retrospective study included 16 eyes from 13 patients with Knapp Class II or III SO palsy. All patients underwent IO disinsertion-distal myectomy and tucking combined with SO full tendon advancement while under general anesthesia. Pre- and post-operative levels of vertical deviation in the primary position, abnormal head position, IO hyperfunction and SO hypofunction, torsion, as well as the presence of diplopia, were all measured, and the differences were statistically compared. Results: Pre-operatively, 12 patients had abnormal head positions, and two had diplopia. The pre-and post-operative levels of IO hyperfunction and SO hypofunction, as well as a vertical deviation in the primary position and torsion, all differed statistically significantly (p < 0.01). Conclusions: Inferior oblique disinsertion distal myectomy and tucking combined with SO full tendon advancement surgery appears to be an effective procedure in patients with congenital and acquired Knapp Class II or III SO palsy. [ABSTRACT FROM AUTHOR]

Understanding mechanisms of ageing remains a complex challenge for biogerontologists, but recent adaptations of evolutionary ageing theories offer a compelling lens in which to view both age-related molecular and physiological deterioration. Ageing is commonly associated with progressive declines in biochemical and molecular processes resulting from damage accumulation, yet the role of continued developmental gene activation is less appreciated. Natural selection pressures are at their highest in youthful periods to modify gene expression towards maximising reproductive capacity. After sexual maturation, selective pressure diminishes, subjecting individuals to maladaptive pleiotropic gene functions that were once beneficial for developmental growth but become pathogenic later in life. Due to this selective 'shadowing' in ageing, mechanisms to counter such hyper/hypofunctional genes are unlikely to evolve. Interventions aimed at targeting gene hyper/hypofunction during ageing might, therefore, represent an attractive therapeutic strategy. The nematode Caenorhabditis elegans offers a strong model for post-reproductive mechanistic and therapeutic investigations, yet studies examining the mechanisms of, and countermeasures against, ageing decline largely intervene from larval stages onwards. Importantly, however, lifespan extending conditions frequently impair early-life fitness and fail to correspondingly increase healthspan. Here, we consolidate multiple evolutionary theories of ageing and discuss data supporting hyper/hypofunctional changes at a global molecular and functional level in C. elegans , and how classical lifespan-extension mutations alter these dynamics. The relevance of such mutant models for exploring mechanisms of ageing are discussed, highlighting that post-reproductive gene optimisation represents a more translatable approach for C. elegans research that is not constrained by evolutionary trade-offs. Where some genetic mutations in C. elegans that promote late-life health map accordingly with healthy ageing in humans, other widely used genetic mutations that extend worm lifespan are associated with life-limiting pathologies in people. Lifespan has also become the gold standard for quantifying 'ageing', but we argue that gerospan compression (i.e., 'healthier' ageing) is an appropriate goal for anti-ageing research, the mechanisms of which appear distinct from those regulating lifespan alone. There is, therefore, an evident need to re-evaluate experimental approaches to study the role of hyper/hypofunctional genes in ageing in C. elegans. [Display omitted] • Views that ageing stems from molecular damage has narrowed our view that hyperactive wild-type genes drive physiological decline. • Systems biology will uncover hyperfunctional expression changes in ageing, enabling late-life gene optimisations to improve health. • Healthy phenotypes of long-lived Caenorhabditis elegans mutants are bound within evolutionary constraints. • There is an urgent need to employ pharmaco-genetic interventions commencing in post-reproductive animals to study healthy ageing. [ABSTRACT FROM AUTHOR]

Objective: The objective of the present study was to investigate the effect of fast speaking on pause duration, breath group duration, and fundamental frequency (F O ) in rote speech (counting)., Method: Twenty-eight healthy women (age 18-39) who had no experience of voice training, repeated a counting task in both a habitual and fast speaking rate. Pause duration, breath group duration, and mean fundamental frequency were measured from audio recordings. Differences in the study variables between habitual and fast speaking rates were analyzed and tested for statistical significance., Results: In fast speaking rate, mean pause duration was shorter and mean breath group duration longer as compared with habitual speaking rate, both with statistical significance at the group level. Surprisingly, mean fundamental frequency was significantly lower in the fast-speaking rate condition., Conclusion: The results overall supported the hypothesis that pause duration becomes shorter and breath group duration longer with a fast-speaking rate. This may have clinical relevance for voice therapy and supports the importance of speaking rate for the understanding and treatment of some hyperfunctional voice disorders. Notably, however, our findings indicated that counting as a speech task induces a specific pattern which may not be comparable to other speech tasks, nor representative of spontaneous speech in every-day-life., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Currently, concern about facial attractiveness is increasing, and this fact has led to orthodontics in adult patients being an increasingly demanded treatment, and with it, multi-disciplinary work. When it is caused by a vertical excess of the maxilla, the ideal solution is orthognathic surgery. However, in borderline cases and when the cause is hyperactivity of the upper lip levator muscle complex, alternative conservative solutions can be considered, such as the application of botulinum toxin A (BTX-A). Botulinum toxin is a protein produced by a bacterium and causes a reduction in the force of muscle contraction. The multi-factorial nature of the smile requires an individualized diagnosis in each patient, since there are multiple ways to treat the gummy smile (orthognathic surgery, gingivoplasty, orthodontic intrusion). In recent years, interest has grown in the simplest techniques that allow the patient to quickly return to their usual routine, such as lip replacement. However, this procedure shows recurrences in the first 6–8 post-operative weeks. The main objective of this systematic review and meta-analysis is to analyze the effectiveness of BTX-A in the treatment of gummy smile in the short term, to study its stability, and to evaluate potential complications. A thorough search of the PubMed, Scopus, Embase, Web of Science, and Cochrane databases and a grey literature search were conducted. The inclusion criteria were studies with a sample size greater than or equal to 10 patients with gingival exposure greater than 2 mm in smile, treated with BTX-A infiltration. Those patients whose exclusive etiology of their gummy smile was related to altered passive eruption, gingival thickening, or overeruption of upper incisors were excluded. In the qualitative analysis, the mean pre-treatment gingival exposure ranged between 3.5 and 7.2 mm, reaching a reduction of up to 6 mm after infiltration with botulinum toxin at 12 weeks. Although multiple muscles are involved in the facial expression, the muscles par excellence selected for blockade with BTX-A were levator labii superioris, levator labii superioris ala nasalis, and zygomaticus minor, infiltrating from 1.25 to 7.5 units per side. In the quantitative analysis, the difference in mean reduction between both groups was −2.51 mm at two weeks and −2.24 mm at three months. The benefit of BTX-A in terms of improvement of gummy smile is demonstrated, as a significant reduction in gummy smile is estimated by BTX-A therapy two weeks after its application. Its results gradually decrease over time, however, they stay satisfactory without returning to their initial values after 12 weeks.

Let P be a minimal parabolic subgroup of a real reductive Lie group G and H a closed subgroup of G. Then it is proved by Kobayashi and Oshima that the regular representation C ∞ (G / H) contains each irreducible representation of G at most finitely many times if the number of H -orbits on G / P is finite. Moreover, they also proved that the multiplicities are uniformly bounded if the number of H ℂ -orbits on G ℂ / B is finite, where G ℂ , H ℂ are complexifications of G , H , respectively, and B is a Borel subgroup of G ℂ . In this paper, we prove that the multiplicities of the representations of G induced from a parabolic subgroup Q in the regular representation on G / H are uniformly bounded if the number of H ℂ -orbits on G ℂ / Q ℂ is finite. For the proof of this claim, we also show the uniform boundedness of the dimensions of the spaces of group invariant hyperfunctions using the theory of holonomic X -modules. [ABSTRACT FROM AUTHOR]

Abstract Classical theory maintains that ageing evolves via energy trade‐offs between reproduction and survival leading to accumulation of unrepaired cellular damage with age. In contrast, the emerging new theory postulates that ageing evolves because of deleterious late‐life hyper‐function of reproduction‐promoting genes leading to excessive biosynthesis in late‐life. The hyper‐function theory uniquely predicts that optimizing nutrient‐sensing molecular signaling in adulthood can simultaneously postpone ageing and increase Darwinian fitness. Here, we show that reducing evolutionarily conserved insulin/IGF‐1 nutrient‐sensing signaling via daf‐2 RNA interference (RNAi) fulfils this prediction in Caenorhabditis elegans nematodes. Long‐lived daf‐2 RNAi parents showed normal fecundity as self‐fertilizing hermaphrodites and improved late‐life reproduction when mated to males. Remarkably, the offspring of daf‐2 RNAi parents had higher Darwinian fitness across three different genotypes. Thus, reduced nutrient‐sensing signaling in adulthood improves both parental longevity and offspring fitness supporting the emerging view that suboptimal gene expression in late‐life lies at the heart of ageing.

The research of multifunctions is a one of the directions in discrete function’s investigations. Multifunction is a discrete function from a finite set A to all subsets of A. The set of hyperfunctions is a subset of set of multifunctions. Hyperfunction is a discrete function from a finite set A to all nonempty subsets of A. The subset relation of hyperfunctions to maximal multiclones is a relation of equivalence and according it all hyperfunctions are divided into equivalence classes. Based on this equivalence it is possible to estimate the cardinality of all possible bases, calculate the number of different types of bases of the same cardinality, and construct some intervals of the clone lattice. Knowing the number of maximal clones, we can obtain upper-bound estimate of the number of such classes as the cardinality of the set of all subsets of the set of maximal clones. It possible to lower this estimate by using properties of the hyperfunctions . A lower-bound estimate for the number of classes can be obtained by constructing the corresponding classes. It is noteworthy that the complexity of the problem of describing all equivalence classes increases essentially with the cardinality of the set of maximal clones increasing. This paper considers multifunctions on a two-element set. The number of maximal multiclones equals to 15 (Panteleyev V.I., 2009). The primary purpose of this research is describing the classification of the set of hyperfunctions into equivalence classes. As Kazimirov A.S. and Panteleyev V.I. showed there are 18 equivalence classes on the set of Boolean functions, which is a subset of the set of hyperfunctions. In this paper were obtained special properties of hyperfunctions and were described all the equivalence classes generated by functions of 3 arguments having applied a computer experiment. The obtained results made it possible to show that the subset relation of hyperfunctions to maximal multiclones splits the set of all hyperfunctions into 67 equivalence classes.

Classical theory maintains that ageing evolves via energy trade‐offs between reproduction and survival leading to accumulation of unrepaired cellular damage with age. In contrast, the emerging new theory postulates that ageing evolves because of deleterious late‐life hyper‐function of reproduction‐promoting genes leading to excessive biosynthesis in late‐life. The hyper‐function theory uniquely predicts that optimizing nutrient‐sensing molecular signaling in adulthood can simultaneously postpone ageing and increase Darwinian fitness. Here, we show that reducing evolutionarily conserved insulin/IGF‐1 nutrient‐sensing signaling via daf‐2 RNA interference (RNAi) fulfils this prediction in Caenorhabditis elegans nematodes. Long‐lived daf‐2 RNAi parents showed normal fecundity as self‐fertilizing hermaphrodites and improved late‐life reproduction when mated to males. Remarkably, the offspring of daf‐2 RNAi parents had higher Darwinian fitness across three different genotypes. Thus, reduced nutrient‐sensing signaling in adulthood improves both parental longevity and offspring fitness supporting the emerging view that suboptimal gene expression in late‐life lies at the heart of ageing. [ABSTRACT FROM AUTHOR]

Patients harboring adrenal tumors are characterized by higher prevalence of metabolic syndrome (MetS) components and a higher incidence of cardiovascular complications, especially in cases of subclinical or overt hormonal hypersecretion. Early detection and referral of those patients in tertiary centers could prevent unfavorable outcomes. In this cross-sectional, retrospective study, we evaluated 111 consecutive patients with adrenal incidentalomas and 14 patients with known hypersecretory adrenal lesions (autonomous cortisol secretion, primary aldosteronism, and pheochromocytoma), who were investigated in our clinic. Based on the different distribution of MetS components in patients with non-functional and functional adrenal lesions we introduced a predictive model of hormonal hypersecretion using those components. We performed multivariate discriminant analysis and compared predictive results with conventional multiple logistic regression analysis. Diabetes, impaired glucose tolerance, impaired fasting glucose, hypertension, body mass index, HDL-cholesterol levels, triglyceride levels, drug treatment for lipid disorder (statins, fenofibrate, and fish oils, alone or in combination), and maximal adrenal lesion diameter were used as discriminating covariates. Multivariate discriminant function exhibited a sensitivity of 77.27 % and specificity of 73.08 % in predicting adrenal hormonal hypersecretion. Receiver operating characteristic curve of discriminant predictive function had an area under the curve value of 0.785, S.E. 0.04. Logistic function delivered comparable results. MetS components exhibit a good predictive feature of hormonal hypersecretion in patients with adrenal tumors. Predictive functions may help in the search for an easy and generally available algorithm to validly predict the functional activity of adrenal masses. [ABSTRACT FROM AUTHOR]

One of the direction in discrete function's investigations is research of functional systems: the sets of functions and the sets of operators defined on this functions. The modern line of inquiry of functional systems deals with generalization of many-valued functions such as partial functions, multifunctions or hyperfunctions. Hyperfunctions are discrete functions from a finite set $A$ to all nonempty subsets of $A$ which closed with respect to the superposition operator. In addition of the superposition operator its interesting to exam more stronger operators which given nontrivial function's classifications. For example, the criterion of completeness for the closure operator with the equality predicate branching on the set of hyperfunctions on two-element set was found. Another well-known strong operator is the parametric closure operator. Twenty five closed classes of Boolean functions is known for this operator. In this work we precise the definition of the parametric closure operator for the set of hyperfunctions and consider this operator on set of hyperfunctions on two-element set. With respect to this operator thirteen closed classes of hyperfunctions are founded. Two of them $S^-$ and $L^-$ are parametric precomplete. The lattice of parametric closed classes of hyperfunctions on two-element set are obtained and parametric bases of this classes are defined.

Background: Noncarious cervical lesions (NCCLs) are rarely described in the periodontal literature, perhaps because no direct link between NCCLs and periodontal lesions has been demonstrated. Aim: The aim of this study is to determine the stress and displacement produced in the tooth at different bone levels under different occlusal load using finite element model (FEM) study. Materials and Methods: Four FEMs of maxillary incisor were designed consisting of the tooth, pulp, periodontal ligament, and alveolar bone at the various level of bone height (25%, 50%, and 75%). Different occlusal load (5 kg, 15 kg, 24 kg, and 29 kg) at an angle of 50° to the long axis of the tooth was applied on the palatal surface at the level of middle third of the crown. All the models were assumed to be isotropic, linear and elastic, and the analysis was performed on a Pentium IV processor computer using the ANSYS software. Results: The maximum stress in the tooth was seen in the cervical region and to a greater extent at the apex for all models. The maximum tooth displacement for all the occlusal loads applied in this study was at the incisal edge with the minimum tooth displacement at the cervical third of the root which shifted apically with the reduction of alveolar bone support. Conclusion: The cumulative effect of increased stress and displacement at the cervical region of the tooth would result in abfraction as the age advances along with other wasting diseases.

Both individuals taking rapamycin, an anti-aging drug, and those not taking it will ultimately succumb to age-related diseases. However, the former, if administered disease-oriented dosages for a long time, may experience a delayed onset of such diseases and live longer. The goal is to delay a particular disease that is expected to be life-limiting in a particular person. Age-related diseases, quasi-programmed during development, progress at varying rates in different individuals. Rapamycin is a prophylactic anti-aging drug that decelerates early development of age-related diseases. I further discuss hyperfunction theory of quasi-programmed diseases, which challenges the need for the traditional concept of aging itself.

In this work we consider the closure operator with the equality predicate branching (E-operator) on the set of hyperfunctions on two-element set. With respect to this operator closed classes of hyperfunctions are generated. We show that there are four submaximal classes and prove the criterion of functional completeness. The relation of equivalence is considered on the set of hyperfunctions obtained by their membership in E-submaximal classes. All hyperfunctions are divided into 14 equivalence classes. In closed sets the minimal closed subsets named basis are derived. We show that basis of hyperfunctions can have cardinality from 1 to 3 and there is no basis with cardinality more than 3. There is only one kind of basis with cardinality 1. The function from that basis does not belong to any of four E-submaximal classes. We obtain 23 kind of basis with cardinality 2 and 11 with cardinality 3.

Let D'L∞(R2n) and A'L∞(R2n) be the spaces of bounded distributions and bounded hyperfunctions respectively. In this paper we consider the Ulam's stability of the sine-cosine functional equation u ...T - u ⊗ v + v ⊗ u ∈ D'L∞(R2n) [resp. A'L∞(R2n)], where u, v are Gelfand hyperfunctions, T : R2n → Rn such that T(x, y) = x - y for all x, y ∈ Rn, and ... ⊗ denote pullback and tensor product of generalized functions respectively. [ABSTRACT FROM AUTHOR]

In this paper, we propose an application of hyperfunction theory to numerical integration. Hyperfunction theory is a generalized version of function theory where functions with singularities such as poles, discontinuities and delta impulses are expressed in terms of complex analytic functions. This feature of hyperfunction theory allows us to construct a numerical integration method for analytic functions. Theoretical error estimates show that our method converges geometrically, and numerical examples show that our method is very efficient especially for integrals with strong end-point singularities. In addition, we present an automatic integration method based on our hyperfunction method. [ABSTRACT FROM AUTHOR]