Comparing stochastic differential equations and agent-based modelling and simulation for early-stage cancer

There is great potential to be explored regarding the use of agent-based modelling and simulation as an alternative paradigm to investigate early-stage cancer interactions with the immune system. It does not suffer from some limitations of ordinary differential equation models, such as the lack of stochasticity, representation of individual behaviours rather than aggregates and individual memory. In this paper we investigate the potential contribution of agent-based modelling and simulation when contrasted with stochastic versions of ODE models using early-stage cancer examples. We seek answers to the following questions: (1) Does this new stochastic formulation produce similar results to the agent-based version? (2) Can these methods be used interchangeably? (3) Do agent-based models outcomes reveal any benefit when compared to the Gillespie results? To answer these research questions we investigate three well-established mathematical models describing interactions between tumour cells and immune elements. These case studies were re-conceptualised under an agent-based perspective and also converted to the Gillespie algorithm formulation. Our interest in this work, therefore, is to establish a methodological discussion regarding the usability of different simulation approaches, rather than provide further biological insights into the investigated case studies. Our results show that it is possible to obtain equivalent models that implement the same mechanisms; however, the incapacity of the Gillespie algorithm to retain individual memory of past events affects the similarity of some results. Furthermore, the emergent behaviour of ABMS produces extra patters of behaviour in the system, which was not obtained by the Gillespie algorithm

Modeling recursive RNA interference.

An important application of the RNA interference (RNAi) pathway is its use as a small RNA-based regulatory system commonly exploited to suppress expression of target genes to test their function in vivo. In several published experiments, RNAi has been used to inactivate components of the RNAi pathway itself, a procedure termed recursive RNAi in this report. The theoretical basis of recursive RNAi is unclear since the procedure could potentially be self-defeating, and in practice the effectiveness of recursive RNAi in published experiments is highly variable. A mathematical model for recursive RNAi was developed and used to investigate the range of conditions under which the procedure should be effective. The model predicts that the effectiveness of recursive RNAi is strongly dependent on the efficacy of RNAi at knocking down target gene expression. This efficacy is known to vary highly between different cell types, and comparison of the model predictions to published experimental data suggests that variation in RNAi efficacy may be the main cause of discrepancies between published recursive RNAi experiments in different organisms. The model suggests potential ways to optimize the effectiveness of recursive RNAi both for screening of RNAi components as well as for improved temporal control of gene expression in switch off-switch on experiments

Changes in body composition and performance with supplemental HMB-FA+ATP (Manuscript Clarification)

Additional co-authors: Matthew D. Vukovich, Colin Wilborn, and Darryn S. Willoughb

The initial characterization of the iron environment in lipoxygenase by MÖssbauer spectroscopy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65879/1/j.1432-1033.1990.tb15616.x.pd

Metabolic responses to the acute ingestion of two commercially available carbonated beverages: A pilot study

<p>Abstract</p> <p>Background</p> <p>The purpose of this placebo-controlled, double-blind cross-over study was to compare the effects of two commercially available soft drinks on metabolic rate.</p> <p>Methods</p> <p>After giving informed consent, twenty healthy men and women were randomly assigned to ingest 12 ounces of Celsius™ and, on a separate day, 12 ounces of Diet Coke®. All subjects completed both trials using a randomized, counterbalanced design. Metabolic rate (via indirect calorimetry) and substrate oxidation (via respiratory exchange ratio) were measured at baseline (pre-ingestion) and at the end of each hour for 3 hours post-ingestion.</p> <p>Results</p> <p>Two-way ANOVA revealed a significant interaction (p < 0.001) between trials in metabolic rate. Scheffe post-hoc testing indicated that metabolic rate increased by 13.8% (+ 0.6 L/min, p < 0.001) 1 hr post, 14.4% (+0.63 L/min, p < 0.001) 2 hr post, and 8.5% (+0.37 L/min, p < 0.004) 3 hr post Celsius™ ingestion. In contrast, small (~4–6%) but statistically insignificant increases in metabolic rate were noted following Diet Coke^®ingestion. No differences in respiratory exchange ratio were noted between trials.</p> <p>Conclusion</p> <p>These preliminary findings indicate Celsius™ has thermogenic properties when ingested acutely. The effects of repeated, chronic ingestion of Celsius™ on body composition are unknown at this time.</p

Resident Cardiac Immune Cells and Expression of the Ectonucleotidase Enzymes CD39 and CD73 after Ischemic Injury

BACKGROUND: The ectoenzymes CD39 and CD73 are expressed by a broad range of immune cells and promote the extracellular degradation of nucleotides to anti-inflammatory adenosine. This study explored the abundance of CD73 and CD39 on circulating and resident cardiac leukocytes and coronary endothelial cells under control conditions and in response to inflammation following myocardial ischemia and reperfusion (I/R). METHODS AND RESULTS: A method was elaborated to permit FACS analysis of non-myocardial cells (resident leukocytes, coronary endothelium and CD31(-) CD45(-) cells) of the unstressed heart. Under control conditions the murine heart contained 2.3 × 10(3) resident leukocytes/mg tissue, the most prominent fraction being antigen-presenting mononuclear cells (CD11b(+) CD11c(+) F4/80(+) MHCII(+)) followed by B-cells, monocytes and T-cells. CD73 was highly expressed on circulating and resident cardiac lymphoid cells with little expression on myeloid cells, while the opposite was true for CD39. Cardiomyocytes and erythrocytes do not measurably express CD39/CD73 and CD39 dominates on coronary endothelium. Three days after I/R, CD73 was significantly upregulated on invading granulocytes (2.8-fold) and T-cells (1.5-fold). Compared with coronary endothelial cells, CD73 associated with leukocytes comprised 2/3 of the total cardiac CD73. CONCLUSION: Our study suggests that extracellular ATP formed during I/R is preferentially degraded by CD39 present on myeloid cells, while the formation of immunosuppressive adenosine is mainly catalysed by CD73 present on granulocytes and lymphoid cells. Upregulated CD73 on granulocytes and T-cells infiltrating the injured heart is consistent with the existence of an autocrine adenosinergic loop which may promote the healing process

International Society of Sports Nutrition Position Stand: Nutrient Timing

Position statement The International Society of Sports Nutrition (ISSN) provides an objective and critical review regarding the timing of macronutrients in reference to healthy, exercising adults and in particular highly trained individuals on exercise performance and body composition. The following points summarize the position of the ISSN. Nutrient timing incorporates the use of methodical planning and eating of whole foods, fortified foods and dietary supplements. The timing of energy intake and the ratio of certain ingested macronutrients may enhance recovery and tissue repair, augment muscle protein synthesis (MPS), and improve mood states following high-volume or intense exercise. Endogenous glycogen stores are maximized by following a high-carbohydrate diet (8–12 g of carbohydrate/kg/day [g/kg/day]); moreover, these stores are depleted most by high volume exercise. If rapid restoration of glycogen is required (\u3c 4 h of recovery time) then the following strategies should be considered: a) aggressive carbohydrate refeeding (1.2 g/kg/h) with a preference towards carbohydrate sources that have a high (\u3e 70) glycemic index b) the addition of caffeine (3–8 mg/kg) c) combining carbohydrates (0.8 g/kg/h) with protein (0.2–0.4 g/kg/h) 4. Extended (\u3e 60 min) bouts of high intensity (\u3e 70% VO2max) exercise challenge fuel supply and fluid regulation, thus carbohydrate should be consumed at a rate of ~30–60 g of carbohydrate/h in a 6–8% carbohydrateelectrolyte solution (6–12 fluid ounces) every 10–15 min throughout the entire exercise bout, particularly in those exercise bouts that span beyond 70 min. When carbohydrate delivery is inadequate, adding protein may help increase performance, ameliorate muscle damage, promote euglycemia and facilitate glycogen re-synthesis. 5. Carbohydrate ingestion throughout resistance exercise (e.g., 3–6 sets of 8–12 repetition maximum [RM] using multiple exercises targeting all major muscle groups) has been shown to promote euglycemia and higher glycogen stores. Consuming carbohydrate solely or in combination with protein during resistance exercise increases muscle glycogen stores, ameliorates muscle damage, and facilitates greater acute and chronic training adaptations. 6. Meeting the total daily intake of protein, preferably with evenly spaced protein feedings (approximately every 3 h during the day), should be viewed as a primary area of emphasis for exercising individuals. 7. Ingestion of essential amino acids (EAA; approximately 10 g)either in free form or as part of a protein bolus of approximately 20–40 g has been shown to maximally stimulate muscle protein synthesis (MPS)

International Society of Sports Nutrition Position Stand: protein and exercise

Abstract Position statement The International Society of Sports Nutrition (ISSN) provides an objective and critical review related to the intake of protein for healthy, exercising individuals. Based on the current available literature, the position of the Society is as follows: 1) An acute exercise stimulus, particularly resistance exercise, and protein ingestion both stimulate muscle protein synthesis (MPS) and are synergistic when protein consumption occurs before or after resistance exercise. 2) For building muscle mass and for maintaining muscle mass through a positive muscle protein balance, an overall daily protein intake in the range of 1.4–2.0 g protein/kg body weight/day (g/kg/d) is sufficient for most exercising individuals, a value that falls in line within the Acceptable Macronutrient Distribution Range published by the Institute of Medicine for protein. 3) There is novel evidence that suggests higher protein intakes (>3.0 g/kg/d) may have positive effects on body composition in resistance-trained individuals (i.e., promote loss of fat mass). 4) Recommendations regarding the optimal protein intake per serving for athletes to maximize MPS are mixed and are dependent upon age and recent resistance exercise stimuli. General recommendations are 0.25 g of a high-quality protein per kg of body weight, or an absolute dose of 20–40 g. 5) Acute protein doses should strive to contain 700–3000 mg of leucine and/or a higher relative leucine content, in addition to a balanced array of the essential amino acids (EAAs). 6) These protein doses should ideally be evenly distributed, every 3–4 h, across the day. 7) The optimal time period during which to ingest protein is likely a matter of individual tolerance, since benefits are derived from pre- or post-workout ingestion; however, the anabolic effect of exercise is long-lasting (at least 24 h), but likely diminishes with increasing time post-exercise. 8) While it is possible for physically active individuals to obtain their daily protein requirements through the consumption of whole foods, supplementation is a practical way of ensuring intake of adequate protein quality and quantity, while minimizing caloric intake, particularly for athletes who typically complete high volumes of training. 9) Rapidly digested proteins that contain high proportions of essential amino acids (EAAs) and adequate leucine, are most effective in stimulating MPS. 10) Different types and quality of protein can affect amino acid bioavailability following protein supplementation. 11) Athletes should consider focusing on whole food sources of protein that contain all of the EAAs (i.e., it is the EAAs that are required to stimulate MPS). 12) Endurance athletes should focus on achieving adequate carbohydrate intake to promote optimal performance; the addition of protein may help to offset muscle damage and promote recovery. 13) Pre-sleep casein protein intake (30–40 g) provides increases in overnight MPS and metabolic rate without influencing lipolysis

International Society of Sports Nutrition Position Stand: protein and exercise

Abstract Position statement The International Society of Sports Nutrition (ISSN) provides an objective and critical review related to the intake of protein for healthy, exercising individuals. Based on the current available literature, the position of the Society is as follows: 1) An acute exercise stimulus, particularly resistance exercise, and protein ingestion both stimulate muscle protein synthesis (MPS) and are synergistic when protein consumption occurs before or after resistance exercise. 2) For building muscle mass and for maintaining muscle mass through a positive muscle protein balance, an overall daily protein intake in the range of 1.4–2.0 g protein/kg body weight/day (g/kg/d) is sufficient for most exercising individuals, a value that falls in line within the Acceptable Macronutrient Distribution Range published by the Institute of Medicine for protein. 3) Higher protein intakes (2.3–3.1 g/kg/d) may be needed to maximize the retention of lean body mass in resistance-trained subjects during hypocaloric periods. 4) There is novel evidence that suggests higher protein intakes (>3.0 g/kg/d) may have positive effects on body composition in resistance-trained individuals (i.e., promote loss of fat mass). 5) Recommendations regarding the optimal protein intake per serving for athletes to maximize MPS are mixed and are dependent upon age and recent resistance exercise stimuli. General recommendations are 0.25 g of a high-quality protein per kg of body weight, or an absolute dose of 20–40 g. 6) Acute protein doses should strive to contain 700–3000 mg of leucine and/or a higher relative leucine content, in addition to a balanced array of the essential amino acids (EAAs). 7) These protein doses should ideally be evenly distributed, every 3–4 h, across the day. 8) The optimal time period during which to ingest protein is likely a matter of individual tolerance, since benefits are derived from pre- or post-workout ingestion; however, the anabolic effect of exercise is long-lasting (at least 24 h), but likely diminishes with increasing time post-exercise. 9) While it is possible for physically active individuals to obtain their daily protein requirements through the consumption of whole foods, supplementation is a practical way of ensuring intake of adequate protein quality and quantity, while minimizing caloric intake, particularly for athletes who typically complete high volumes of training. 10) Rapidly digested proteins that contain high proportions of essential amino acids (EAAs) and adequate leucine, are most effective in stimulating MPS. 11) Different types and quality of protein can affect amino acid bioavailability following protein supplementation. 12) Athletes should consider focusing on whole food sources of protein that contain all of the EAAs (i.e., it is the EAAs that are required to stimulate MPS). 13) Endurance athletes should focus on achieving adequate carbohydrate intake to promote optimal performance; the addition of protein may help to offset muscle damage and promote recovery. 14) Pre-sleep casein protein intake (30–40 g) provides increases in overnight MPS and metabolic rate without influencing lipolysis