Identical Growth Rates Research Articles

A fractographic study of fatigue crack growth from a cold expanded fastener hole at an engineering “crack initiation” scale

AbstractThe effects of cold expansion on fatigue crack growth from fastener holes in aircraft structure are a well‐studied problem, with many contributions focusing on both residual stresses and “long crack” experimental data. In this study, the authors have used quantitative fractography techniques to measure fatigue crack growth from naturally occurring discontinuities on an engineering “crack initiation” scale. Fatigue crack growth rates were measured through the full range of crack depths, allowing the effects of beneficial residual stresses to be directly observed. The almost identical early crack growth rates in cold expanded and non‐cold expanded specimens were demonstrated up to crack depths of approximately 0.1–0.2 mm. Beyond this depth, fatigue crack growth in cold expanded specimens was markedly slowed to the point at which failure ultimately arose from cracks away from, or growing into, the fastener hole. The available life improvement factor for cold expansion is therefore maximized through a crack growth‐based lifing approach.

Global dynamics of 3D cooperative Lotka-Volterra system with the identical intrinsic growth rate

In this paper, we complete the classification on global topological structures of the three-dimensional cooperative Lotka-Volterra system with the identical intrinsic growth rate inside the Poincaré compactification of the positive octant of R3. Precisely, with the help of the replicator equations it is proved that this kind of system can have exactly 8 topologically different phase portraits. As a consequence, we obtain the necessary and sufficient conditions for the system to be bounded in the positive octant.

Dietary 1,3-β-Glucans Affect Growth, Breast Muscle Composition, Antioxidant Activity, Inflammatory Response, and Economic Efficiency in Broiler Chickens.

Recently, researchers have been intensively looking for novel, safe antibiotic alternatives because of the prevalence of many clinical and subclinical diseases affecting bird flocks and the risks of using antibiotics in subtherapeutic doses as feed additives. The present study intended to evaluate the potential use of 1,3-β-glucans (GLC) as antibiotic alternative growth promotors and assessed the effect of their dietary inclusion on the growth performance, carcass traits, chemical composition of breast muscles, economic efficiency, blood biochemical parameters, liver histopathology, antioxidant activity, and the proinflammatory response of broiler chickens. This study used 200 three-day-old ROSS broiler chickens (50 chicks/group, 10 chicks/replicate, with an average body weight of 98.71 ± 0.17 g/chick). They were assigned to four experimental groups with four dietary levels of GLC, namely 0, 50, 100, and 150 mg kg-1, for a 35-day feeding period. Birds fed diets containing GLC showed an identical different growth rate to the control group. However, the total feed intake (TFI) increased quadratically in the GLC50 and GLC100 groups as compared to that in the control group. GLC addition had no significant effect on the weights of internal and immune organs, except for a decrease in bursal weight in the GLC150 group (p = 0.01). Dietary GLC addition increased the feed cost and total cost at 50 and 100 mg kg-1 doses. The percentages of n-3 and n-6 PUFA in the breast muscle of broiler chickens fed GLC-supplemented diets increased linearly in a dose-dependent manner (p < 0.01). The serum alanine aminotransferase (ALT) level and the uric acid level were quadratically increased in the GLC150 group. The serum levels of total antioxidant capacity, catalase, superoxide dismutase, interleukin-1β, and interferon-gamma linearly increased, while the MDA level decreased in the GLC-fed groups in a dose-dependent manner. Normal histological characterization of different liver structures in the different groups with moderate round cells was noted as a natural immune response around the hepatic portal area. The different experimental groups showed an average percentage of positive immunostaining to the proinflammatory marker transforming growth factor-beta with an increase in the dose of GLC addition. The results suggest that GLC up to 100 mg kg-1 concentration can be used as a feed additive in the diets of broiler chickens and shows no adverse effects on their growth, dressing percentage, and internal organs. GLC addition in diets improves the antioxidant activity and immune response in birds. GLC help enrich the breast muscle with n-3 and n-6 polyunsaturated fatty acids.

Assessment of environmental sustainability of nickel required for mobility transition

Nickel (Ni) in batteries (e.g., nickel-metal hydride battery (NiMH), lithium nickel cobalt aluminum oxide (NCA) and lithium nickel manganese cobalt oxide (NMC)) aim to ensure higher energy density and greater storage capacity. Two typical layered nickel-rich ternary cathode materials, NCA and NMC, are commercialized as advanced lithium-ion batteries (LiBs) for electric vehicles (EVs). The technology of those batteries has been improving by steadily increasing the nickel content in each cathode generation. In this study, we consider two types of batteries having a composite cathode made of Li [Ni0.80Co0.1Al0.1]O2, and Li [Ni0.33Mn0.33Co0.33]O2, which are the most common cathode materials for LiBs in EVs since 2010 and their functional recycling is performed. The increasing use of nickel in battery technologies has resulted in the continuous growth of demand for nickel over recent years. Nickel was added to the list of critical materials by the United States Geological Survey (USGS) already in 2021. Unfortunately now, the sustainable supply of nickel is even at higher risk due to the sanctions-related disruption of supplies from Russia. Therefore, enhancing the circularity of nickel starts to be vital for many economies. Demand for recycled nickel is growing, however, a systematic analysis of the sustainability of its recycling is still missing. Therefore, we provide a comprehensive assessment of the sustainability of the global primary and secondary production of nickel. Using system dynamics modelling integrated with geometallurgy principles and by analyzing the processing routes (pyrometallurgical and hydrometallurgical processes), we quantify the key environmental concerns across the life cycle of primary and secondary nickel required for sustainable mobility transition. Energy consumption, water use, and related emissions are assessed for all stages of the nickel supply chain, from mining to recycling. Our analysis shows the possibility of reducing the emissions by around 4.7 mt for GHG, 6.9 kt for PM2.5, 34.3 t for BC, 2.8 kt for CH4, 7.5 kt for CO, 3.3 mt for CO2, 169.9 t for N2O, 3.8 kt for NOx, 11.8 kt for PM10, 104.8 t for POC, 1.6 mt for SOx, and 232.5 t for VOC by engaging in the secondary production of nickel through the recycling of batteries. However, identical growth rate of energy consumption and water use compared to nickel mass flows means no technical progress has been achieved in different stages of the nickel supply chain towards sustainability over the period 2010–2030. Therefore, an improvement in technology is needed to save energy and water in nickel production processes. The results and findings of this study contribute to a better understanding of the necessity for improving closed-loop supply chain policies for nickel.

Role of avalanche transport in competing drift wave and interchange turbulence

We complete the 2D 2-fields turbulence model previously used with an interchange-like instability by slightly modifying the parallel loss terms to drive drift wave instabilities. We show that the instability driven by temperature fluctuations of the sheath losses is identical to that of the drift wave turbulence. The linear analysis is performed and used to select control parameters that yield identical maximum growth rates for the interchange alone and drift wave alone instability. Combining the two instabilities doubles the maximum growth rate. The non-linear simulations are used to analyse the SOL width. The simulations allow one to identify a low field side SOL region where interchange and drift wave are unstable and a high field side SOL region where only the drift wave is unstable. The SOL profiles appear exponential in the region close to the source but depart from a simple exponential fall-off in the far SOL. The low field side SOL width is found to be larger in the interchange alone case, slightly smaller when both instabilities are present and finally narrower when only the drift waves. For the high field side SOL, without interchange, the drift wave SOL width is observed to be identical to that on the low field side and larger than that when both instabilities at play. The Sherwood dimensionless parameter, ratio of convective particle flux divided by the diffusive particle flux, is used to compare the efficiency of turbulent transport. The profiles of the Sherwood parameter for time and flux surface averaged transport indicate that turbulent transport is dominant close to the separatrix but is less effective towards the far SOL. The Sherwood parameter evolution, determined with the flux-surface averaged transport, indicates that outward avalanche transport with corrugations governs the case with interchange only. When combining the two instabilities, outward avalanche transport is less pronounced and inward avalanche transport is observed, reducing the overall turbulent transport efficiency. The avalanche transport with drift waves only compared to interchange only is found to be inhibited.

Examining the role of water vapor on small fatigue crack growth behavior in Ti-6242S using ultrasonic fatigue and scanning electron microscopy

The influence of water vapor on small fatigue crack growth rates in the near alpha titanium alloy Ti-6242S was investigated using a combined ultrasonic fatigue/environmental scanning electron microscope system (UF-SEM). Small fatigue cracks were grown at a cyclic frequency of 20 kHz in laboratory air, partial pressures of water vapor ranging from 65 to 1330 Pa, and vacuum (1.7 × 10-4 Pa). Fatigue cracks grew at higher rates in all water vapor pressures investigated versus in vacuum, with a nearly identical growth rate observed in laboratory air and 1330 Pa water vapor. A linear dependence of small fatigue crack growth rate on water vapor pressure was observed that is consistent with a pressure dependent transport rate of water vapor molecules to the crack-tip. This work indicates that the amount of water vapor present in the environment (humidity) plays an important role in determining the fatigue life of Ti-6242S and must be accounted for even at very high cyclic frequencies, such as the 20 kHz cyclic frequency commonly employed in ultrasonic fatigue testing.

Scan4CFU: Low-cost, open-source bacterial colony tracking over large areas and extended incubation times

A hallmark of bacterial populations cultured in vitro is their homogeneity of growth, where the majority of cells display identical growth rate, cell size and content. Recent insights, however, have revealed that even cells growing in exponential growth phase can be heterogeneous with respect to variables typically used to measure cell growth. Bacterial heterogeneity has important implications for how bacteria respond to environmental stresses, such as antibiotics. The phenomenon of antimicrobial persistence, for example, has been linked to a small subpopulation of cells that have entered into a state of dormancy where antibiotics are no longer effective. While methods have been developed for identifying individual non-growing cells in bacterial cultures, there has been less attention paid to how these cells may influence growth in colonies on a solid surface. In response, we have developed a low-cost, open-source platform to perform automated image capture and image analysis of bacterial colony growth on multiple nutrient agar plates simultaneously. The descriptions of the hardware and software are included, along with details about the temperature-controlled growth chamber, high-resolution scanner, and graphical interface to extract and plot the colony lag time and growth kinetics. Experiments were conducted using a wild type strain of Escherichia coli K12 to demonstrate the feasibility and operation of our setup. By automated tracking of bacterial growth kinetics in colonies, the system holds the potential to reveal new insights into understanding the impact of microbial heterogeneity on antibiotic resistance and persistence.

A Comparison of Tree Growth in Two Sites near Schefferville, Quebec

This aim of this study is to determine if there are differences in tree growth between two sites near Schefferville, Quebec (located at 54°48′N,&nbsp;&nbsp;66°50′W): the Ephemeral Lake and Airport Woodland site. Tree core samples were collected in order to determine if the “stressed” condition might make a difference in the growth of the trees within the site, and to evaluate how trees may adapt to particular conditions. Cores were collected from 20 trees in the 100x100 meter stressed site, Ephemeral Lake. Core samples were taken from 30 trees located in the in the 10x10 meter ideal site, Airport Woodland.Analysis of the tree cores showed that that there was no statistically significant difference in rate of trunk circumference (or diameter) growth, but rather, both the stressed and ideal forests displayed nearly identical growth rates. This seems to indicate that trees in both plots had similar amounts of water to facilitate their annual growth rate. However, average tree height and average vertical growth per year are highly statistically significant, and are thus found to be key factors. Trees in the stressed forest grow slower upwards (but not in thickness) than trees in the ideal forest, and they reach lower total height—by a factor of almost two—than trees in the ideal forest.If we assume, for example, that the stressed forest under study constitutes a random sample of trees that, in a sense, comes from a population of “all stressed forests,” and similarly for the “ideal forest,” then we may conclude that stressed forests—ones exposed to heavy winds and facing unreliable water supply—tend to produce shorter and slower-growing trees than do forests under “ideal” conditions. Equally, the non-significance of the width-growth variable can indicate that it is not necessarily true that tree-width and tree-width-growth-rate are adversely affected by stressed environment.On the other hand, there were differences in the heights—or lengths of trunks—of trees in the two groups. First, trees in the stressed group were less likely to be growing vertically. About half of the trees in the stressed group were tilted or growing with their main trunk underground. The trees in the ideal group, on the other hand, were nearly all growing vertically, with only a single tree identified as “slanted” rather than “straight.” Also, the trees in the stressed group grew upward at a slower rate than those in the ideal group, and displayed lower overall heights.&nbsp

Balance simplices of 3-species May-Leonard systems

We investigate the existence of a two-dimensional invariant manifold that attracts all nonzero orbits in 3 species Lotka-Volterra systems with identical linear growth rates. This manifold, which we call the balance simplex, is the common boundary of the basin of repulsion of the origin and the basin of repulsion of infinity. The balance simplex is linked to ecological models where there is ‘growth when rare’ and competition for finite resources. By including alternative food sources for predators we cater for predator-prey type models. In the case that the model is competitive, the balance simplex coincides with the carrying simplex which is an unordered manifold (no two points may be ordered componentwise), but for non-competitive models the balance simplex need not be unordered. The balance simplex of our models contains all limit sets and is the graph of a piecewise analytic function over the unit probability simplex.

Comparative Palm Oil Trade Performance in Indonesia, Malaysia, and the Philippines

Purpose – As one of the most traded commodities in the world with tremendous economic significance, palm oil is an inexpensive source of oil. This paper examined and compared the palm oil trade performance of the Philippines relative to its top palm oil producing neighbors, Indonesia and Malaysia, by analyzing import-export volume trends of the said food commodity, consumption and production trends, self-sufficiency, import dependence, and shifting patterns of comparative advantage. Design/Methodology/Approach – Secondary data covering the period from 1964 through 2018 were collected from various sources, and descriptive analysis coupled with trend analysis were employed with respect to import and export, production, and consumption performance. Other trade indicators were computed, to wit: balance of trade, self-sufficiency ratio, import dependency ratio, and normalized trade balance. Implications were drawn after the comparative analysis among the three countries was done. Findings – An increase in the volume of the palm oil supply in the Philippines is evident, and this is attributed to increasing importation. Relative to Malaysia and Indonesia, the Philippines lags behind in international trade. While Philippine palm oil industry growth has been stagnant in terms of international trade by virtue of its net importer status, Malaysia and Indonesia have overtaken the country significantly, having attained self-sufficiency in the commodity with trade surpluses, and the gap is expected to widen in the coming years. It is interesting to note that the Philippines, Malaysia, and Indonesia had identical production volumes and growth rates until the last decade of the 21st century. A steadily growing industry, palm oil is foreseen to continue being a vital industry, not only to top producing countries such as Malaysia and Indonesia but also in the Philippines, which is trying to improve its palm oil trade performance by expanding production. Research Implications – The study findings imply expansion and income opportunities not only for local oil palm producers, processors, and traders in the Philippines but also for foreign market entrants.

Global dynamics of 3D competitive Lotka-Volterra equations with the identical intrinsic growth rate

This paper focuses on investigating complete global topological classification of the three dimensional competitive Lotka-Volterra system with the identical intrinsic growth rate in the compactification of the positive octant of R3 including its infinity. The system is divided into 37 topological classes among 33 stable nullcline classes by the relation on the parameters of competitive system.

A large-scale investigation of stress response mechanisms in the industrial yeast Kluyveromyces marxianus

Microbial production strains need to operate under sub- optimal growth conditions such as low pH, high osmolarity and thermal stress. The capacity to carry out industrial fermentations at higher temperatures reduces the risk of bacterial contamination and lowers cooling costs. We want to understand the basis of thermotolerance in the industrial yeast Kluyveromyces marxianus. As part of the EU-funded project, CHASSY, K. marxianus was grown in chemostat cultures under different stress conditions and a multi-omics analysis performed to study a range of stress responses, including elevated temperature (40 °C). Transcriptomes were generated from steady state cultures growing at identical growth rates under different stress conditions and gene set enrichment analysis (GSEA) performed. A range of functions were identified as being specifically expressed at higher temperatures and these are now being further investigated. One example is the temperature-specific expression of two putative hexose transport genes. Subsequent mutational inactivation using CRISPR and heterologous complementation established that at least one of these two genes is required for growth at (40 °C). We are now trying to determine the substrates for, and the precise function of, these genes. We also developed a ribosome profiling pipeline for K. marxianus and are using this to investigate the translational response to temperature stress. The combined study of both transcription and translation at steady state and as a culture responds to a temperature shift will give a comprehensive view of the basis of thermotolerance in K. marxianus and should identify strategies to exploit this in biotechnological processes.

On the validity of Zeeman's classification for three dimensional competitive differential equations with linearly determined nullclines

We study three dimensional competitive differential equations with linearly determined nullclines and prove that they always have 33 stable nullcline classes in total. Each class is given in terms of inequalities on the intrinsic growth rates and competitive coefficients and is independent of generating functions. The common characteristics are that every trajectory converges to an equilibrium in classes 1–25, that Hopf bifurcations do not occur within class 32, and that there is always a heteroclinic cycle in class 27. Nontrivial dynamical behaviors, such as the existence and multiplicity of limit cycles, only may occur in classes 26–33, but these nontrivial dynamical behaviors depend on generating functions. We show that Hopf bifurcation can occur within each of classes 26–31 for continuous-time Leslie/Gower system and Ricker system, the same as Lotka–Volterra system; but it only occurs in classes 26 and 27 for continuous-time Atkinson/Allen system and Gompertz system. There is an apparent distinction between Lotka–Volterra system and Leslie/Gower system, Ricker system, Atkinson/Allen system, and Gompertz system with the identical growth rate. Lotka–Volterra system with the identical growth rate has no limit cycle, but admits a center on the carrying simplex in classes 26 and 27. But Leslie/Gower system, Ricker system, Atkinson/Allen system, and Gompertz system with the identical growth rate do possess limit cycles. At last, we provide examples to show that Leslie/Gower system and Ricker system can also admit two limit cycles. This general classification greatly widens applications of Zeeman's method and makes it possible to investigate the existence and multiplicity of limit cycles, centers and stability of heteroclinic cycles for three dimensional competitive systems with linearly determined nullclines, as done in planar systems.

Invariance of multifractal spectrums of spatial forms on the surface of ZnxCd1-xTe – Si heterocompositions synthesized by electron beam epitaxy and hot wall epitaxy

Multifractal (MF) analysis is applied for the description of spatial nanoforms which form a relief on a surface of heterostructures of ZnxCd1-xTe solid solution – substrate Si (111) synthesized by the method of the electron beam with the evaporating anode. The input data for the MF analysis were the AFM (atomic force microscopy) images of the surface of layers. Comparison of parameters of MF spectrums for different geometries of the surface relief of the layers obtained at identical temperatures and approximately identical growth rates by the above mentioned method of growth and the method of hot wall epitaxy has been performed.It was shown that within the error limits, MF spectrums of spatial nanoforms for heterostructures ZnxCd1-xTe – Si remained very similar under identical conditions for synthesis of layers for compared techniques.

Isothermal-crystallization kinetics and spherulite growth of aliphatic polyketone/polyamide-6 blends

In this research, the morphologies, isothermal-crystallization kinetics, and spherulite growth of aliphatic polyketone/polyamide-6 blends were studied. A single glass-transition temperature (T g) was determined, and the composition dependence of T g for these blends was well described by the Kwei equation. The strong intermolecular interaction between the two polymer components was confirmed by melting-point depression. The isothermal-crystallization kinetics were analyzed on the basis of the Avrami approach. A linear increase in the radii of the spherulites with time was observed for all compositions. All the spherulites continued to grow at nearly identical growth rates. With increasing polyamide-6 content, the size of the spherulites in the polyketone/polyamide-6 blends gradually decreased, and the number of spherulites in the blends increased.

Outdoor Growth Characterization of an Unknown Microalga Screened from Contaminated Chlorella Culture.

Outdoor microalgae cultivation process is threatened by many issues, such as pest pollution and complex, changeable weather. Therefore, it is difficult to have identical growth rate for the microalgae cells and to keep their continuous growth. Outdoor cultivation requires the algae strains not only to have a strong ability to accumulate oil, but also to adapt to the complicated external environment. Using 18S rRNA technology, one wild strain Scenedesmus sp. FS was isolated and identified from the culture of Chlorella zofingiensis. Upon contamination by Scenedesmus sp., the species could quickly replace Chlorella zofingiensis G1 and occupy ecological niche in the outdoor column photobioreactors. The results indicated that Scenedesmus sp. FS showed high alkali resistance. It also showed that even under the condition of a low inoculum rate (OD680, 0.08), Scenedesmus sp. FS could still grow in the outdoor raceway pond under a high alkaline environment. Even under unoptimized conditions, the oil content of Scenedesmus sp. FS could reach more than 22% and C16–C18 content could reach up to 79.68%, showing that this species has the potential for the biodiesel production in the near future.

Non-constant discounting and Ak-type growth models

This paper analyzes an Ak-type endogenous growth model under non-constant discounting, assuming both naive and sophisticated consumers. For both types of consumers an isoelastic utility with an intertemporal elasticity below one guarantees observational equivalence under exponential and non-constant discounting, but rejects strong equivalence (identical overall impatience does not lead to identical growth rates). Further, polices aimed at increasing productivity of the economy are less growth-enhancing than typically predicted by the literature with exponential discounting.

An endophyte-rich diet increases ant predation on a specialist herbivorous insect

1. All plants form symbioses with microfungi, known as endophytes, which live within plant tissues. Numerous studies have documented endophyte–herbivore antagonism in grass systems, but plant–endophyte–insect interactions are highly variable for forbs and woody plants. 2. The net effect of endophytes on insect herbivory may be modified by their interactions with higher trophic levels, such as predators. Including these multitrophic dynamics may explain some of the variability among endophyte studies of non-grass plants, which are currently based exclusively on bitrophic studies. 3. The abundance of natural foliar endophytes in a Neotropical vine was manipulated and beetles were fed high or low endophyte diets. Experimental assays assessed whether dietary endophyte load affected beetle growth, leaf consumption, and susceptibility to ant predation. 4. Beetles feeding on high- versus low-endophyte plants had almost identical growth and leaf consumption rates. 5. In a field bioassay, however, it was discovered that feeding on an endophyte-rich diet increased a beetle's odds of capture by predatory ants nine-fold. 6. Endophytes could thus provide an indirect, enemy-mediated form of plant defence that operates even against specialist herbivores. We argue that a multitrophic approach is necessary to untangle the potentially diverse types of endophyte defence among plants.

Nitrogen Utilization and Metabolism in Ruminococcus albus 8

The model rumen Firmicutes organism Ruminococcus albus 8 was grown using ammonia, urea, or peptides as the sole nitrogen source; growth was not observed with amino acids as the sole nitrogen source. Growth of R. albus 8 on ammonia and urea showed the same growth rate (0.08 h(-1)) and similar maximum cell densities (for ammonia, the optical density at 600 nm [OD600] was 1.01; and for urea, the OD600 was 0.99); however, growth on peptides resulted in a nearly identical growth rate (0.09 h(-1)) and a lower maximum cell density (OD600 = 0.58). To identify differences in gene expression and enzyme activities, the transcript abundances of 10 different genes involved in nitrogen metabolism and specific enzyme activities were analyzed by harvesting mRNA and crude protein from cells at the mid- and late exponential phases of growth on the different N sources. Transcript abundances and enzyme activities varied according to nitrogen source, ammonia concentration, and growth phase. Growth of R. albus 8 on ammonia and urea was similar, with the only observed difference being an increase in urease transcript abundance and enzyme activity in urea-grown cultures. Growth of R. albus 8 on peptides showed a different nitrogen metabolism pattern, with higher gene transcript abundance levels of gdhA, glnA, gltB, amtB, glnK, and ureC, as well as higher activities of glutamate dehydrogenase and urease. These results demonstrate that ammonia, urea, and peptides can all serve as nitrogen sources for R. albus and that nitrogen metabolism genes and enzyme activities of R. albus 8 are regulated by nitrogen source and the level of ammonia in the growth medium.

Uracil DNA glycosylase (UNG) loss enhances DNA double strand break formation in human cancer cells exposed to pemetrexed

Misincorporation of genomic uracil and formation of DNA double strand breaks (DSBs) are known consequences of exposure to TS inhibitors such as pemetrexed. Uracil DNA glycosylase (UNG) catalyzes the excision of uracil from DNA and initiates DNA base excision repair (BER). To better define the relationship between UNG activity and pemetrexed anticancer activity, we have investigated DNA damage, DSB formation, DSB repair capacity, and replication fork stability in UNG+/+ and UNG−/− cells. We report that despite identical growth rates and DSB repair capacities, UNG−/− cells accumulated significantly greater uracil and DSBs compared with UNG+/+ cells when exposed to pemetrexed. ChIP-seq analysis of γ-H2AX enrichment confirmed fewer DSBs in UNG+/+ cells. Furthermore, DSBs in UNG+/+ and UNG−/− cells occur at distinct genomic loci, supporting differential mechanisms of DSB formation in UNG-competent and UNG-deficient cells. UNG−/− cells also showed increased evidence of replication fork instability (PCNA dispersal) when exposed to pemetrexed. Thymidine co-treatment rescues S-phase arrest in both UNG+/+ and UNG−/− cells treated with IC50-level pemetrexed. However, following pemetrexed exposure, UNG−/− but not UNG+/+ cells are refractory to thymidine rescue, suggesting that deficient uracil excision rather than dTTP depletion is the barrier to cell cycle progression in UNG−/− cells. Based on these findings we propose that pemetrexed-induced uracil misincorporation is genotoxic, contributing to replication fork instability, DSB formation and ultimately cell death.