Scaling in a continuous time model for biological aging

In this paper we consider a generalization to the asexual version of the Penna model for biological aging, where we take a continuous time limit. The genotype associated to each individual is an interval of real numbers over which Dirac $\delta$--functions are defined, representing genetically programmed diseases to be switched on at defined ages of the individual life. We discuss two different continuous limits for the evolution equation and two different mutation protocols, to be implemented during reproduction. Exact stationary solutions are obtained and scaling properties are discussed.Comment: 10 pages, 6 figure

Measurement of disruption forces in JET using fiber-optic sensors

Monitoring the forces induced on the vacuum vessel when a disruption occurs is essential for the protection of the machine. Since divertor coils have been installed in JET, during disruptions a significant difference between the forces measured on the top and the bottom of the machine has been observed. In order to investigate these further, optical fiber transducers FBGs (Fiber Bragg Gratings) were installed in addition to the currently used strain gauges. During VDE (Vertical Displacement Event) tests, these new transducers were used to measure different level of disruptions ranging from 80T up to 230T vertical forces. The results were then compared with the strain gauges. The FBG measurement was carried out using a broadband light source illuminating an array of 4 FBGs through a combination of directional couplers, connectors and fiber-optic cable. The forces measured both by FBG and by the strain gauges are within the same range, except for the initial swing where large random differences are observed. The tests have demonstrated that the FBG-based force measurement system has adequate resolution (±1.52strain corresponding to a force of 4kN due to the geometry of the leg) and measurement range (50002strain or 13000kN) for this application

Catastrophic senescence and semelparity in the Penna aging model

The catastrophic senescence of the Pacific salmon is among the initial tests used to validate the Penna aging model. Based on the mutation accumulation theory, the sudden decrease in fitness following reproduction may be solely attributed to the semelparity of the species. In this work, we report other consequences of mutation accumulation. Contrary to earlier findings, such dramatic manifestation of aging depends not only on the choice of breeding strategy but also on the value of the reproduction age, R, and the mutation threshold, T. Senescence is catastrophic when $T \leq R$. As the organism's tolerance for harmful genetic mutations increases, the aging process becomes more gradual. We observe senescence that is threshold dependent whenever T>R. That is, the sudden drop in survival rate occurs at age equal to the mutation threshold value

Concept level evaluation of the full-scale deployment of fibre Bragg grating sensors for measuring forces in JET during plasma disruption events

This paper discusses concept level evaluation of the full-scale deployment of fibre bragg grating sensors for measuring forces in JET during plasma disruption events

Mechanical testing and modelling of the Universal 2 implant

Understanding the load mechanics of orthopaedic implants is important to be able to predict their behaviour in-vivo. Much research, both mechanical and clinical, has been carried out on hip and knee implants, but less has been written about the mechanics of wrist implants. In this paper, the load mechanics of the Universal 2 wrist implant have been measured using two types of measuring techniques, strain gauges and Fibre Bragg Grating measurements to measure strains. The results were compared to a finite element model of the implant. The results showed that the computational results were in good agreement with the experimental results. Better understanding of the load mechanics of wrist implants, using models and experimental results can catalyse the development of future generation implants

Why Y chromosome is shorter and women live longer?

We have used the Penna ageing model to analyze how the differences in evolution of sex chromosomes depend on the strategy of reproduction. In panmictic populations, when females (XX) can freely choose the male partner (XY) for reproduction from the whole population, the Y chromosome accumulates defects and eventually the only information it brings is a male sex determination. As a result of shrinking Y chromosome the males become hemizygous in respect to the X chromosome content and are characterized by higher mortality, observed also in the human populations. If it is assumed in the model that the presence of the male is indispensable at least during the pregnancy of his female partner and he cannot be seduced by another female at least during the one reproduction cycle - the Y chromosome preserves its content, does not shrink and the lifespan of females and males is the same. Thus, Y chromosome shrinks not because of existing in one copy, without the possibility of recombination, but because it stays under weaker selection pressure; in panmictic populations without the necessity of being faithful, a considerable fraction of males is dispensable and they can be eliminated from the population without reducing its reproduction potential.Comment: 8 pages, 5 figure

Polygenic Study of Endurance-Associated Genetic Markers NOS3 (Glu298Asp), BDKRB2 (-9/+9), UCP2 (Ala55Val), AMPD1 (Gln45Ter) and ACE (I/D) in Polish Male Half Marathoners

The purpose of this study was to investigate individually and in combination the association between the ACE (I/D), NOS3 (Glu298Asp), BDKRB2 (-9/+9), UCP2 (Ala55Val) and AMPD1 (Gln45Ter) variants with endurance performance in a large, performance-homogenous cohort of elite Polish half marathoners. The study group consisted of 180 elite half marathoners: 76 with time 100 minutes. DNA of the subjects was extracted from buccal cells donated by the runners and genotyping was carried out using an allelic discrimination assay with a C1000 Touch Thermal Cycler (Bio-Rad, Germany) instrument with TaqMan® probes (NOS3, UCP2, and AMPD1) and a T100™ Thermal Cycler (Bio-Rad, Germany) instrument (ACE and BDKRB2). We found that the UCP2 Ala55Val polymorphism was associated with running performance, with the subjects carrying the Val allele being overrepresented in the group of most successful runners (100 min group (84.2 vs. 55.8%; OR = 4.23, p 100 min group (73.7 vs. 51.9%; OR = 2.6, p = 0.0034). These data suggest that the likelihood of becoming an elite half marathoner partly depends on the carriage of a high number of endurance-related alleles

Pyruvate kinase M2 activation may protect against the progression of diabetic glomerular pathology and mitochondrial dysfunction

Diabetic nephropathy (DN) is a major cause of end-stage renal disease, and therapeutic options for preventing its progression are limited. To identify novel therapeutic strategies, we studied protective factors for DN using proteomics on glomeruli from individuals with extreme duration of diabetes (≥ 50 years) without DN and those with histologic signs of DN. Enzymes in the glycolytic, sorbitol, methylglyoxal and mitochondrial pathways were elevated in individuals without DN. In particular, pyruvate kinase M2 (PKM2) expression and activity were upregulated. Mechanistically, we showed that hyperglycemia and diabetes decreased PKM2 tetramer formation and activity by sulfenylation in mouse glomeruli and cultured podocytes. Pkm-knockdown immortalized mouse podocytes had higher levels of toxic glucose metabolites, mitochondrial dysfunction and apoptosis. Podocyte-specific Pkm2-knockout (KO) mice with diabetes developed worse albuminuria and glomerular pathology. Conversely, we found that pharmacological activation of PKM2 by a small-molecule PKM2 activator, TEPP-46, reversed hyperglycemia-induced elevation in toxic glucose metabolites and mitochondrial dysfunction, partially by increasing glycolytic flux and PGC-1α mRNA in cultured podocytes. In intervention studies using DBA2/J and Nos3 (eNos) KO mouse models of diabetes, TEPP-46 treatment reversed metabolic abnormalities, mitochondrial dysfunction and kidney pathology. Thus, PKM2 activation may protect against DN by increasing glucose metabolic flux, inhibiting the production of toxic glucose metabolites and inducing mitochondrial biogenesis to restore mitochondrial function