Exploring tradeoffs in pleiotropy and redundancy using evolutionary computing

Evolutionary computation algorithms are increasingly being used to solve optimization problems as they have many advantages over traditional optimization algorithms. In this paper we use evolutionary computation to study the trade-off between pleiotropy and redundancy in a client-server based network. Pleiotropy is a term used to describe components that perform multiple tasks, while redundancy refers to multiple components performing one same task. Pleiotropy reduces cost but lacks robustness, while redundancy increases network reliability but is more costly, as together, pleiotropy and redundancy build flexibility and robustness into systems. Therefore it is desirable to have a network that contains a balance between pleiotropy and redundancy. We explore how factors such as link failure probability, repair rates, and the size of the network influence the design choices that we explore using genetic algorithms.Comment: 10 pages, 6 figure

Luminal Ca2+–regulated Mg2+ Inhibition of Skeletal RyRs Reconstituted as Isolated Channels or Coupled Clusters

In resting muscle, cytoplasmic Mg2+ is a potent inhibitor of Ca2+ release from the sarcoplasmic reticulum (SR). It is thought to inhibit calcium release channels (RyRs) by binding both to low affinity, low specificity sites (I-sites) and to high affinity Ca2+ sites (A-sites) thus preventing Ca2+ activation. We investigate the effects of luminal and cytoplasmic Ca2+ on Mg2+ inhibition at the A-sites of skeletal RyRs (RyR1) in lipid bilayers, in the presence of ATP or modified by ryanodine or DIDS. Mg2+ inhibits RyRs at the A-site in the absence of Ca2+, indicating that Mg2+ is an antagonist and does not simply prevent Ca2+ activation. Cytoplasmic Ca2+ and Cs+ decreased Mg2+ affinity by a competitive mechanism. We describe a novel mechanism for luminal Ca2+ regulation of Ca2+ release whereby increasing luminal [Ca2+] decreases the A-site affinity for cytoplasmic Mg2+ by a noncompetitive, allosteric mechanism that is independent of Ca2+ flow. Ryanodine increases the Ca2+ sensitivity of the A-sites by 10-fold, which is insufficient to explain the level of activation seen in ryanodine-modified RyRs at nM Ca2+, indicating that ryanodine activates independently of Ca2+. We describe a model for ion binding at the A-sites that predicts that modulation of Mg2+ inhibition by luminal Ca2+ is a significant regulator of Ca2+ release from the SR. We detected coupled gating of RyRs due to luminal Ca2+ permeating one channel and activating neighboring channels. This indicated that the RyRs existed in stable close-packed rafts within the bilayer. We found that luminal Ca2+ and cytoplasmic Mg2+ did not compete at the A-sites of single open RyRs but did compete during multiple channel openings in rafts. Also, luminal Ca2+ was a stronger activator of multiple openings than single openings. Thus it appears that RyRs are effectively “immune” to Ca2+ emanating from their own pore but sensitive to Ca2+ from neighboring channels

Optimization of protein recovery from bovine lung by pH shift process using response surface methodology

peer-reviewedBACKGROUND Response surface methodology (RSM) was used in a sequential manner to optimize solubilization and precipitation conditions in the recovery of protein from bovine lung using pH shift. RESULTS Separate D‐optimal designs were employed for protein solubilization and precipitation. Independent variables investigated for protein solubilization were time (10–120 min), temperature (4–20 °C), pH (8.0–11.0) and solvent/sample ratio (2.5–10). Variables for protein precipitation were time (0–60 min) and pH (4.25–6.00). Soluble protein yields ranged from 323 to 649 g kg−1 and the quadratic model for protein solubilization revealed a coefficient of determination R2 of 0.9958. Optimal conditions for maximum protein solubility were extraction time 140 min, temperature 19 °C, pH 10.8 and solvent/sample ratio 13.02. Protein precipitation yields varied from 407 to 667 g kg−1, giving a coefficient of determination R2 of 0.9335. Optimal conditions for maximum protein precipitation were pH 5.03 and 60 min. Based on the RSM model, solubilization conditions were manipulated to maximize protein solubilization under reduced water and alkaline usage. These conditions were also validated. CONCLUSION Models for solubilization and precipitation using bovine and porcine lung were validated; predicted and actual yields were in good agreement, showing cross‐species applicability of the results. © 2017 Society of Chemical Industr

Families of graphs with maximum nullity equal to zero forcing number

The maximum nullity of a simple graph G, denoted M(G), is the largest possible nullity over all symmetric real matrices whose ijth entry is nonzero exactly when fi, jg is an edge in G for i =6 j, and the iith entry is any real number. The zero forcing number of a simple graph G, denoted Z(G), is the minimum number of blue vertices needed to force all vertices of the graph blue by applying the color change rule. This research is motivated by the longstanding question of characterizing graphs G for which M(G) = Z(G). The following conjecture was proposed at the 2017 AIM workshop Zero forcing and its applications: If G is a bipartite 3- semiregular graph, then M(G) = Z(G). A counterexample was found by J. C.-H. Lin but questions remained as to which bipartite 3-semiregular graphs have M(G) = Z(G). We use various tools to find bipartite families of graphs with regularity properties for which the maximum nullity is equal to the zero forcing number; most are bipartite 3-semiregular. In particular, we use the techniques of twinning and vertex sums to form new families of graphs for which M(G) = Z(G) and we additionally establish M(G) = Z(G) for certain Generalized Petersen graphs

Submission to the independent review of the Student Grant Scheme by The Department of Further and Higher Education, Research, Innovation and Science Department of Adult and Community Education, Maynooth University

The Department of Adult and Community Education, Maynooth University, welcome this opportunity to contribute to the consultation for the independent review of the Student Grant Scheme by The Department of Further and Higher Education, Research, Innovation and Science. Based on consultation with staff and students in our department, we present key discussion points and recommendations below about the current SUSI eligibility criteria and grant support, the potential impact of changing income thresholds and of widening the supports to include part time provision, postgraduate programme, FET learners and blended/online provision. Since its establishment in 1974, the Department of Adult and Community Education (DACE) in Maynooth University has focused on meeting the educational needs of diverse groups in our society, supporting the transformation of lives and communities through adult and community education to create a just, equitable and sustainable society. Our work is informed by the experiences of students and staff of the department through programmes ranging from outreach certificates and diplomas, undergraduate and post-graduate programmes to thousands of students from diverse backgrounds on campus and across outreach centres nationally over the past 40 years. Our work is set within a broader context where Maynooth University welcomes students from diverse backgrounds, including having approximately half of its 1st year full-time undergraduate new entrants in receipt of a student grant, the highest proportion of students in receipt of a grant in the University sector (HEA 2015, 2017). We consulted with staff and students in our department to explore their experiences and opinions on the student award system, including those in receipt of SUSI and those who are not currently eligible. We also consulted with the Communiversity Network of community based adult education coordinators and adult guidance services who are advocates for lifelong learning among the most disadvantaged groups. The document that follows is informed by the insights provided by these students, staff and community actors. In particular, we wish to highlight issues about current income thresholds and the costs of higher education; diverse student pathways and knowledge about progression; and the rationale and impacts of widening the supports to include part time provision, postgraduate programme, FET learners and blended/online provision

Resolution of inflammation:state of the art, definitions and terms

A recent focus meeting on Controlling Acute Inflammation was held in London, April 27-28, 2006, organized by D.W. Gilroy and S.D. Brain for the British Pharmacology Society. We concluded at the meeting that a consensus report was needed that addresses the rapid progress in this emerging field and details how the specific study of resolution of acute inflammation provides leads for novel anti-inflammatory therapeutics, as well as defines the terms and key components of interest in the resolution process within tissues as appreciated today. The inflammatory response protects the body against infection and injury but can itself become dysregulated with deleterious consequences to the host. It is now evident that endogenous biochemical pathways activated during defense reactions can counter-regulate inflammation and promote resolution. Hence, resolution is an active rather than a passive process, as once believed, which now promises novel approaches for the treatment of inflammation-associated diseases based on endogenous agonists of resolution

Hypoxia-induced responses by endothelial colony-forming cells are modulated by placental growth factor

BACKGROUND: Endothelial colony-forming cells (ECFCs), also termed late outgrowth endothelial cells, are a well-defined circulating endothelial progenitor cell type with an established role in vascular repair. ECFCs have clear potential for cell therapy to treat ischaemic disease, although the precise mechanism(s) underlying their response to hypoxia remains ill-defined. METHODS: In this study, we isolated ECFCs from umbilical cord blood and cultured them on collagen. We defined the response of ECFCs to 1% O(2) exposure at acute and chronic time points. RESULTS: In response to low oxygen, changes in ECFC cell shape, proliferation, size and cytoskeleton phenotype were detected. An increase in the number of senescent ECFCs also occurred as a result of long-term culture in 1% O(2). Low oxygen exposure altered ECFC migration and tube formation in Matrigel®. Increases in angiogenic factors secreted from ECFCs exposed to hypoxia were also detected, in particular, after treatment with placental growth factor (PlGF). Exposure of cells to agents that stabilise hypoxia-inducible factors such as dimethyloxalylglycine (DMOG) also increased PlGF levels. Conditioned medium from both hypoxia-treated and DMOG-treated cells inhibited ECFC tube formation. This effect was reversed by the addition of PlGF neutralising antibody to the conditioned medium, confirming the direct role of PlGF in this effect. CONCLUSIONS: This study deepens our understanding of the response of ECFCs to hypoxia and also identifies a novel and important role for PlGF in regulating the vasculogenic potential of ECFCs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13287-016-0430-0) contains supplementary material, which is available to authorized users

Chlamydia trachomatis from Australian Aboriginal people with trachoma are polyphyletic composed of multiple distinctive lineages.

Chlamydia trachomatis causes sexually transmitted infections and the blinding disease trachoma. Current data on C. trachomatis phylogeny show that there is only a single trachoma-causing clade, which is distinct from the lineages causing urogenital tract (UGT) and lymphogranuloma venerum diseases. Here we report the whole-genome sequences of ocular C. trachomatis isolates obtained from young children with clinical signs of trachoma in a trachoma endemic region of northern Australia. The isolates form two lineages that fall outside the classical trachoma lineage, instead being placed within UGT clades of the C. trachomatis phylogenetic tree. The Australian trachoma isolates appear to be recombinants with UGT C. trachomatis genome backbones, in which loci that encode immunodominant surface proteins (ompA and pmpEFGH) have been replaced by those characteristic of classical ocular isolates. This suggests that ocular tropism and association with trachoma are functionally associated with some sequence variants of ompA and pmpEFGH