Balance between asymmetric allocation and repair of somatic damage in unicellular life forms as an ancient form of r/K selection.

Over the course of multiple divisions, cells accumulate diverse nongenetic, somatic damage including misfolded and aggregated proteins and cell wall defects. If the rate of damage accumulation exceeds the rate of dilution through cell growth, a dedicated mitigation strategy is required to prevent eventual population collapse. Strategies for somatic damage control can be divided into two categories, asymmetric allocation and repair, which are not, in principle, mutually exclusive. We explore a mathematical model to identify the optimal strategy, maximizing the total cell number, over a wide range of environmental and physiological conditions. The optimal strategy is primarily determined by extrinsic, damage-independent mortality and the physiological model for damage accumulation that can be either independent (linear) or increasing (exponential) with respect to the prior accumulated damage. Under the linear regime, the optimal strategy is either exclusively repair or asymmetric allocation, whereas under the exponential regime, the optimal strategy is a combination of asymmetry and repair. Repair is preferred when extrinsic mortality is low, whereas at high extrinsic mortality, asymmetric damage allocation becomes the strategy of choice. We hypothesize that at an early stage of life evolution, optimization over repair and asymmetric allocation of somatic damage gave rise to r and K selection strategists.

Application of the thermal death time model in predicting thermal damage accumulation in plants.

The thermal death time (TDT) model suggests that the duration for which an organism can tolerate thermal stress decreases exponentially as the intensity of the temperature becomes more extreme. This model has been used to predict damage accumulation in ectothermic animals and plants under fluctuating thermal conditions. However, the critical assumption of the TDT model, which is additive damage accumulation, remains unverified for plants. We assessed thermal damage in Thymus vulgaris under different heat and cold treatments, and used TDT models to predict time to thermal failure of PSII. Additionally, thermal tolerance estimates from previous studies were used to create TDT models to assess the applicability of this framework in plants. We show that thermal damage is additive between 44 °C and 47 °C and between -6.5 °C and -8 °C, and that the TDT model can predict damage accumulation at both temperature extremes. Data from previous studies indicate a broad applicability of this approach across plant species and traits. The TDT framework reveals a thermal tolerance landscape describing the relationship between exposure duration, stress intensity, and percentage damage accumulation. The extreme thermal sensitivity of plants emphasizes that even a 1 °C increase in future extreme temperatures could impact their mortality and distribution.

How soon do metabolic alterations and oxidative distress precede the reduction of muscle mass and strength in Wistar rats in aging process?

Here we investigate metabolic changes, the antioxidant system and the accumulation of oxidative damage in muscles with different fiber types during the aging process in Wistar rats and try to map how sooner the changes occur. To do so, 30 male Wistar rats were submitted to behavioral evaluation to determine voluntary strength in the 11, 15, and 19 month old rats, measuring the energy metabolism, antioxidant system, oxidative damage and structure in the soleus and extensor digitorum longus muscles. We detected structural and metabolic changes in both muscles, especially in the EDL of 15 month old rats and in the soleus of 19 month old rats. In the 15 month old rats, there was a reduction in the cross-sectional area of the fibers, and a reduction in the proportion of type I fibers, accompanied by an increase in fiber density and the amount of type IIA fibers. This change in the fiber profile was followed by an increase in the activity of anaerobic metabolism enzymes, suggesting a reduction in the oxidative capacity of the muscle. In addition, there was an increase in the rate of lipid peroxidation, accompanied by a reduced antioxidant capacity. In the 19 month old rats, these disturbances got stronger. In summary, the present study demonstrated that before functional disturbances, there was an accumulation of oxidative damage and structural changes in the skeletal muscle beginning at 15 months old in the EDL and the soleus only in the biochemical parameters. Therefore, the metabolic alterations occurred at 15 months old and not before.

Varied approaches to loading assessment in fatigue studies.

In this paper, the authors want to draw readers' attention to one long-standing question: which approach is preferable for estimation longevities in fatigue problem, the time domain approach (Rainflow) or the frequency domain one (Dirlik and others)? This question is important in engineering problems, particularly in problems of prolongation of the guaranteed service life. The discussion here is restricted by the longevity evaluation only at the post-processing stage of unidirectional loaded machine parts. It means the realizations might be recorded. Some experimental and speculative evidence of preferable use the Rainflow method is shown. Taking into account the huge computer's power nowadays, the question of the irrelevance of appellation to the calculation accelerating using the spectral methods is specially discussed. There are areas, where the spectral methods are really necessary. There is only a need to recommend the restriction of their application scope to these special situations. It seems there is no need in inventing new spectral complicated algorithms only to stress out at the end, that their result coincides with the Rainflow outcome. That might be confusing for the practicing engineers. Currently, the main attention among supporters of spectral methods is focused on non-stationary and non-Gaussian random processes. (to estimate the spectral density is impossible for non-stationary processes, according to definition). These researchers seem to have forgotten, that even for these complicated situations the decision has already existed: that is the Rainflow and its analogues. The paper shows extensive laboratory experiment results of random fatigue testing of aluminum flat specimens under regular (to build the fatigue curve) and irregular (random) loading. The fatigue life curve (Gassner curve) has been built. These results allowed to compare the existing computation methods of longevity estimation. In the particular situation of narrow-band process, the methods seem to provide comparative results. Considered are methodological issues related to the assessment of the necessary and sufficient realization length, the influence of RMS, cycle counting methods and some possibilities of computing resources saving when using the Rainflow method. The stability of the Rainflow estimates is confirmed. Some problems with the choice of parameters during the longevity assessment by the Dirlik method were noted.

Evolution of ageing as a tangle of trade-offs: energy versus function.

Despite tremendous progress in recent years, our understanding of the evolution of ageing is still incomplete. A dominant paradigm maintains that ageing evolves due to the competing energy demands of reproduction and somatic maintenance leading to slow accumulation of unrepaired cellular damage with age. However, the centrality of energy trade-offs in ageing has been increasingly challenged as studies in different organisms have uncoupled the trade-off between reproduction and longevity. An emerging theory is that ageing instead is caused by biological processes that are optimized for early-life function but become harmful when they continue to run-on unabated in late life. This idea builds on the realization that early-life regulation of gene expression can break down in late life because natural selection is too weak to optimize it. Empirical evidence increasingly supports the hypothesis that suboptimal gene expression in adulthood can result in physiological malfunction leading to organismal senescence. We argue that the current state of the art in the study of ageing contradicts the widely held view that energy trade-offs between growth, reproduction, and longevity are the universal underpinning of senescence. Future research should focus on understanding the relative contribution of energy and function trade-offs to the evolution and expression of ageing.

Damage-Fitness Model: the missing piece in integrative stress models.

Over the last decade, several theoretical models have been put forth to describe how animals respond to adverse environments and how this response changes under different physiological demands across life history stages. These models capture the context- and condition-dependent nature of stress responses. Yet, application of the models has been limited thus far in part because each model addresses different aspects of the problems facing the field of stress biology. Thus, there is a need for a unifying theoretical model that incorporates changes in physiological demand with life history stages and age, intricate relationships among physiological systems, and biphasic nature of stress responses. Here, I propose a new integrative framework, the Damage-Fitness Model. In this model, regulators, such as DNA repair mechanisms and glucocorticoids, work together as anti-damage mechanisms to minimize damage at both the cellular and organismal level. When the anti-damage regulators are insufficient or inappropriate, persistent damage accumulates. Previous studies indicate that these damage directly impact reproductive performance, disease risk, and survival. The types of regulators, the threshold at which they are initiated, and the magnitude of the responses are shaped by developmental and current environments. This model unites existing theoretical models by shifting our focus from physiological responses to downstream consequences of the stress responses, circumventing context specificity. Discussions include (1) how the proposed model relates to existing models, (2) steps to test the new model, and (3) how this model can be used to better assess the health of individuals and a population. Lay summary The field of stress physiology faces a challenge of characterizing dynamic cellular, physiological, and behavioral responses when animals encounter a stressor. This paper proposes a new theoretical model which links stress avoidance, damage repair and accumulation, and fitness components.

The protective function of non-coding DNA in DNA damage accumulation with age and its roles in age-related diseases.

Aging is a progressive decline of physiological function in tissue and organ accompanying both accumulation of DNA damage and reduction of non-coding DNA. Peripheral non-coding DNA/heterochromatin has been proposed to protect the genome and centrally-located protein-coding sequences in soma and male germ cells against radiation and the invasion of exogenous nucleic acids. Therefore, this review summarizes the reduction of non-coding DNA/heterochromatin (including telomeric DNA and rDNA) and DNA damage accumulation during normal physiological aging and in various aging-related diseases. Based on analysis of data, it is found that DNA damage accumulation is roughly negatively correlated with the reduction of non-coding DNA and therefore speculated that DNA damage accumulation is likely due to the reduction of non-coding DNA protection in genome defense during aging. Therefore, it is proposed here that means to increase the total amount of non-coding DNA and/or heterochromatin prior to the onset of these diseases could potentially better protect the genome and protein-coding DNA, reduce the incidence of aging-related diseases, and thus lead to better health during aging.

Combination of DESI2 and endostatin gene therapy significantly improves antitumor efficacy by accumulating DNA lesions, inducing apoptosis and inhibiting angiogenesis.

DESI2 is a novel pro-apoptotic gene. We previously reported that DESI2 overexpression induces S phase arrest and apoptosis by activating checkpoint kinases. This work was to test whether the combination of endostatin, an endogenous antiangiogenic inhibitor, with DESI2 could improve the therapy efficacy in vitro and in vivo. The recombinant plasmid co-expressing DESI2 and endostatin was encapsulated with DOTAP/Cholesterol cationic liposome. Mice bearing CT26 colon carcinoma and LL2 lung cancer were treated with the DNA-liposome complex. We found that, in vitro, the combination of DESI2 and endostatin more efficiently inhibited proliferation of CT26, LL2, HCT116 and A549 cancer cells via apoptosis, as assessed by MTT assay, colony-formation assays, flow cytometric analysis, hoechst staining and activation of caspase-3, respectively. In addition, DESI2 overexpression caused up-regulation of RPS7, a substrate of DESI2 deubiquitination. Furthermore, siRNA targeting RPS7 partially abrogated, whereas RPS7 overexpression enhanced DESI2-induced inhibition of cell proliferation. Importantly, the combination also caused DNA lesions accumulation, which further promotes apoptosis. Mechanistic rationale suggested that endostatin first inhibits DNA-PKcs kinase, and partly abrogated DESI2-induced phosphorylation of DNA-PKcs, leading to increase of DNA damage, then contributes to DESI2-induced apoptosis. In vivo, the combined gene therapy more significantly inhibited tumor growth and efficiently prolonged the survival of tumor bearing mice than mono therapy. The improved antitumor effect was associated with inhibition of cell proliferation via apoptosis, as analyzed by TUNEL assay and PCNA immunostaining. The combination also inhibited angiogenesis, as assessed by alginate-encapsulated tumor cell assay and CD31 staining. Our data suggest that the combined gene therapy of DESI2 and endostatin can significantly enhance the antitumor activity as a DNA lesions accumulator, apoptosis inducer and angiogenesis inhibitor. The present study may provide a novel method for the treatment of cancer.

Age and years to death disparately influence reproductive allocation in a short-lived bird.

Theory predicts that reproduction will change as individuals near the end of their lives by either increasing reproductive allocation (terminal allocation hypothesis) or decreasing allocation (senescence hypothesis) toward the end of life. Although senescence has received more support, few studies examine how both age and years to death influence late-life reproduction. We used a 37-yr study of Song Sparrows (Melospiza melodia) to ask how age and years to death influenced reproductive allocation late in life. We observed both senescence and terminal allocation, and that age and years to death interacted to influence individual variation in allocation tactics. In particular, we observed a decline in allocation in older individuals (senescence), but only when comparing individuals with the same number of years to death. Likewise, we observed terminal allocation, but only in young females. Reproductive tactics were most variable in young females, with many exerting high effort but living 1-2 yr, and others exerting low effort annually and living longer. Our results suggest that late-life reproductive tactics are influenced by both chronological age and years to death, and that short- and long-lived females with differing reproductive tactics exist within this population of Song Sparrows.

Self-Sensing of Damage Progression in Unidirectional Multiscale Hierarchical Composites Subjected to Cyclic Tensile Loading.

The electrical sensitivity of glass fiber/multiwall carbon nanotube/vinyl ester hierarchical composites containing a tailored electrically-percolated network to self-sense accumulation of structural damage when subjected to cyclic tensile loading-unloading is investigated. The hierarchical composites were designed to contain two architectures differentiated by the location of the multiwall carbon nanotubes (MWCNTs), viz. MWCNTs deposited on the fibers and MWCNTs dispersed within the matrix. The changes in electrical resistance of the hierarchical composites are associated to their structural damage and correlated to acoustic emissions. The results show that such tailored hierarchical composites are able to self-sense damage onset and accumulation upon tensile loading-unloading cycles by means of their electrical response, and that the electrical response depends on the MWCNT location.

Microstructural aspects of fatigue in Ni-base superalloys.

Nickel-base superalloys are primarily used as components in jet engines and land-based turbines. While compositionally complex, they are microstructurally simple, consisting of small (50-1000 nm diameter), ordered, coherent Ni(3)(Al,Ti)-type L1(2) or Ni(3)Nb-type DO(22) precipitates (called γ(') and γ(''), respectively) embedded in an FCC substitutional solid solution consisting primarily of Ni and other elements which confer desired properties depending upon the application. The grain size may vary from as small as 2 µm for powder metallurgy alloys used in discs to single crystals the actual size of the component for turbine blades. The fatigue behaviour depends upon the microstructure, deformation mode, environment and cycle time. In many cases, it can be controlled or modified through small changes in composition which may dramatically change the mechanism of damage accumulation and the fatigue life. In this paper, the fundamental microstructural, compositional, environmental and deformation mode factors which affect fatigue behaviour are critically reviewed. Connections are made across a range of studies to provide more insight. Modern approaches are pointed out in which the wealth of available microstructural, deformation and damage information is used for computerized life prediction. The paper ends with a discussion of the very important and highly practical subject of thermo-mechanical fatigue (TMF). It is shown that physics-based modelling leads to significantly improved life prediction. Suggestions are made for moving forward on the critical subject of TMF life prediction in notched components.

Comprehensive modeling of annulus fibrosus: From biphasic refined characterization to damage accumulation under viscous loading.

The annulus fibrosus (AF), a permeable, hydrated, and fiber-reinforced soft tissue, exhibits complex responses influenced by fluid pressure, osmotic pressure, and structural mechanics. Existing models struggle to comprehensively represent these intricate interactions and the heterogeneous solid responses within the AF. Additionally, the mechanisms driving differential damage accumulation between non-degenerative and degenerative intervertebral discs remain poorly understood. In this study, we introduce a biphasic-swelling damage model for the AF. We conceptually develop and rigorously validate this model through tissue-level tests employing various loading modes, consistently aligning model predictions with experimental data. Leveraging parametric geometric algorithms and custom Python scripts, we construct models simulating both non-degenerative and degenerative discs. Following calibration, we subject these models to viscous loading protocols. Our findings reveal the posterior AF's susceptibility to damage, contingent upon loading rate and water content. We elucidate the underlying mechanisms by examining the temporal evolution of fluid pressure, osmotic pressure, and the regionally dependent fiber network. This research presents a highly accurate model of the AF, providing valuable insights into disc damage. Future research endeavors should expand this model to incorporate ionic transport and diffusion, enabling a more profound exploration of intervertebral disc mechanobiology. This comprehensive model contributes to a better understanding of AF behavior and may inform therapeutic strategies for disc-related pathologies. STATEMENT OF SIGNIFICANCE: This research presents a comprehensive model of the annulus fibrosus (AF), a crucial component of the intervertebral disc that provides structural support and resists deformation. The study introduces a biphasic-swelling damage model for the AF and validates it through tissue-level tests. The model accounts for fluid pressure, osmotic pressure, and matrix mechanics, providing a more accurate representation of the AF's behavior. The study also investigates the differential damage accumulation between non-degenerative and degenerative discs, shedding light on the mechanisms driving disc degeneration. The findings have significant implications for medical treatments and interventions, as they highlight the posterior AF's susceptibility to damage. This research is of great interest to readers interested in biomechanics, tissue engineering, and medical treatments for disc degeneration.

Dynamic Response and Damage Accumulation of Laminated Composites under Repeated Low-Velocity Impacts.

The mechanical response and damage accumulation of carbon-fiber-reinforced composite laminates subjected to repeated low-velocity impacts were experimentally investigated. The repeated impact tests were conducted on [902/-452/02/452]S quasi-isotropic and [902/02]2S cross-ply composite laminates under 16.8 J impact energy, respectively. For each impact, impact responses such as force-time, force-displacement and energy-time curves were recorded. The trends of peak force, maximum central displacement, energy absorption rate and bending stiffness with the increasing impact number were summarized, and the maximum number of repeated impacts corresponded to the occurrence of penetration events. The results showed that the delamination initiation, fiber breakage and penetration were the three typical characteristics describing the damage evolution of the repeated impacts. The damage accumulation of both the laminates was characterized by employing appropriate damage indices. By contrast, the quasi-isotropic laminates had higher impact resistance and damage tolerance, and their damage accumulation was relatively slower.

Mechanical Properties Degradation of Fiberglass Tubes during Biaxial Proportional Cyclic Loading.

Composite structures during an operation are subjected to various types of external loading (impact, vibration, cyclic, etc.), which may lead to a decrease in mechanical properties. Previously, many experimental investigations of the mechanical behavior of composites under uniaxial cyclic loading were carried out. Acquisition of new data on the reduction of composite materials' mechanical characteristics under conditions of multiaxial cyclic loading, as well as verification of existing models for calculation of the residual properties, are relevant. Therefore, this work is devoted to the experimental investigation of the mechanical behavior of fiberglass tubes under proportional cyclic loading. Static and fatigue tests were carried out under tension with torsion conditions. Inhomogeneous strain fields were obtained using a non-contact optical video system VIC-3D. The structural damage accumulation processes were analyzed by an AMSY-6 acoustic emission signals recording system. Surface defects were determined using a DinoLite microscope. Residual dynamic elastic modules were calculated during fatigue tests, and fatigue sensitivity curves were built. Data was approximated using various models, and their high descriptive capability was revealed. Damage accumulation stages were determined. The dependence of the models' parameters on a stress state were observed. It was concluded that multiaxial cyclic loading leads to a significant decrease in mechanical properties, which should be taken into account in composite structure design.

Cumulative Fatigue Damage of Composite Laminates: Engineering Rule and Life Prediction Aspect.

The analysis of cumulative fatigue damage is an important factor in predicting the life of composite elements and structures that are exposed to field load histories. A method for predicting the fatigue life of composite laminates under varying loads is suggested in this paper. A new theory of cumulative fatigue damage is introduced grounded on the Continuum Damage Mechanics approach that links the damage rate to cyclic loading through the damage function. A new damage function is examined with respect to hyperbolic isodamage curves and remaining life characteristics. The nonlinear damage accumulation rule that is presented in this study utilizes only one material property and overcomes the limitations of other rules while maintaining implementation simplicity. The benefits of the proposed model and its correlation with other relevant techniques are demonstrated, and a broad range of independent fatigue data from the literature is used for comparison to investigate its performance and validate its reliability.

Risk factors of young males with physically demanding occupations having accumulated damage of anterior cruciate ligament.

OBJECTIVE: To present the clinical characteristics of accumulated anterior cruciate ligament (ACL) damage among young male patients undergoing routine exercise, and to evaluate the related risk factors. METHODS: A retrospective study involving ACL-accumulated damage from June 2015 to December 2019 was conducted. Baseline characteristics, such as age, body mass index (BMI), training parameters, and clinical signs, were recorded. The results of the radiologic examinations and related standardized tests were obtained to evaluate the research outcomes. These results were compared using Student's t-test or Chi-square test, and the impact of risk factors on the patient's injury were analyzed. RESULTS: A total of 86 men with accumulated ACL damage were included in this study. Exercise pain (86 [100%]), synovitis (80 [93.0%]), and intra-articular effusion (79 [91.9%]) were the most common clinical symptoms. Loosening of ligaments, decreased tension, mild hyperplasia, and intercondylar fossa effusion were observed using radiography, magnetic resonance imaging, and arthroscopy. Age, BMI, training intensity, length of training, and knee hyperextension were identified as risk factors for accumulated ACL damage. CONCLUSION: This study suggests that accumulated ACL damage has differentiated clinical symptoms, imaging features, and risk factors compared to common ACL injuries.

Investigating the Effect of Low-Temperature Drilling Process on the Mechanical Behavior of CFRP.

Previous research has found that lower temperature drilling is helpful to improve the hole quality of carbon fiber reinforced polymer (CFRP). However, the influence of the lower temperature drilling process on the mechanical behavior of composites is yet not fully understood. To examine the influence of the lower temperature drilling process on the mechanical behavior of CFRP, the open hole CFRP specimens used for mechanical tests were obtained with three cases: drilling with -25 °C/uncoated carbide drills/(1000 rpm, 0.02 mm/r), 23 °C/coated carbide drills/(4000 rpm, 0.03 mm/r), and 23 °C/uncoated carbide drills/(1000 rpm, 0.02 mm/r), respectively; corresponding, three groups of open-hole specimens are obtained: specimens drilling at low-temperature with low damage, specimens drilling at room-temperature with low damage and specimens drilling at room-temperature with low damage; the mechanical behavior of the three groups specimens were obtained by static tensile, tensile-tensile fatigue cyclic tests and residual tensile strength test. The results have shown that the mechanical properties of specimens with a low-temperature drilling process is lower than those of the specimen with a normal drilling process due to the better drilling quality. The damage accumulation in specimens was increased with the damage degree of the original hole, the greater the damage degree, the worse the mechanical properties.

Microstructure-Based Computational Analysis of Deformation Stages of Rock-like Sandy-Cement Samples in Uniaxial Compression.

This work presents a new finite-difference continuum damage mechanics approach for assessment of threshold stresses based on the mechanical response of a representative volume element of a sandy-cement rock-like material. An original experimental study allows validating the mathematical model. A new modification of the damage accumulation kinetic equation is proposed. Several approaches based on acoustic emission, instantaneous Poisson's ratio and reversal point method are employed to determine the threshold stresses. Relying on the numerical modeling of deformation and failure of model samples, the threshold stresses and the deformation stages are determined. The model predicts the crack initiation stress threshold with less than 10% error. The model prediction of the crack damage stress threshold corresponds to the upper boundary of the experimental range. The model predicts the peak stress threshold with less than 0.2% error in comparison with the average experimental peak stress. The results of numerical modeling are shown to correlate well with the available experimental and literature data and sufficiently complement them.

Non-Linear Probabilistic Modification of Miner's Rule for Damage Accumulation.

A non-linear modification to Miner's rule for damage accumulation is proposed to reduce the scatter between experimental fatigue life and fatigue life predicted according to the original Miner's sum. Based on P-s-n probability distribution and design s-n curves, the modification satisfies the assumption of equality between the mean damage degree (at the critical level) and fatigue life random variables, which is not covered in the original formulation. The adopted formulation shows the discrepancies between the fatigue lives predicted according to the design s-n curves and the estimated probability distribution. It also proves that it is inappropriate to apply a normal distribution to fatigue life analysis and that the model becomes non-linear only for non-normal distributions. The predictions according to the established model were compared to the predictions obtained with Miner's rule.

Investigation of Changes in Fatigue Damage Caused by Mean Load under Block Loading Conditions.

The literature in the area of material fatigue indicates that the fatigue properties may change with the number of cycles. Researchers recommend taking this into account in fatigue life calculation algorithms. The results of simulation research presented in this paper relate to an algorithm for estimating the fatigue life of specimens subjected to block loading with a nonzero mean value. The problem of block loads using a novel calculation model is presented in this paper. The model takes into account the change in stress-strain curve parameters caused by mean strain. Simulation tests were performed for generated triangular waveforms of strains, where load blocks with changed mean strain values were applied. During the analysis, the degree of fatigue damage was compared. The results of calculations obtained for standard values of stress-strain parameters (for symmetric loads) and those determined, taking into account changes in the curve parameters, are compared and presented in this paper. It is shown that by neglecting the effect of the mean strain value on the K' and n' parameters and by considering only the parameters of the cyclic deformation curve for εm = 0 (symmetric loads), the ratio of the total degree of fatigue damage varies from 10% for εa = 0.2% to 3.5% for εa = 0.6%. The largest differences in the calculation for ratios of the partial degrees of fatigue damage were observed in relation to the reference case for the sequence of block n3, where εm = 0.4%. The simulation results show that higher mean strains change the properties of the material, and in such cases, it is necessary to take into account the influence of the mean value on the material response under block loads.