Allogeneic HSCT in Adolescents and Young Adults With Primary Immunodeficiencies

Significant advances in hematopoietic transplantation over the past 20 years, have facilitated the safe transplantation of older adults with higher co-morbidities. In pediatric practice these advances have simultaneously improved outcomes for sicker children with complex, rare diseases including the primary immunodeficiencies, PID. With more widespread adoption of genetic sequencing, older patients with disease-causing mutations restricted to the hematopoietic system can be identified who may benefit from allogeneic hematopoietic stem cell transplantation (Allo-HSCT). Here we discuss the evidence for Allo-HSCT in adolescent and younger adults (AYAs) with PID

Letter graphs and geometric grid classes of permutations: characterization and recognition

In this paper, we reveal an intriguing relationship between two seemingly unrelated notions: letter graphs and geometric grid classes of permutations. An important property common for both of them is well-quasi-orderability, implying, in a non-constructive way, a polynomial-time recognition of geometric grid classes of permutations and $k$-letter graphs for a fixed $k$. However, constructive algorithms are available only for $k=2$. In this paper, we present the first constructive polynomial-time algorithm for the recognition of $3$-letter graphs. It is based on a structural characterization of graphs in this class.Comment: arXiv admin note: text overlap with arXiv:1108.6319 by other author

A colimit decomposition for homotopy algebras in Cat

Badzioch showed that in the category of simplicial sets each homotopy algebra of a Lawvere theory is weakly equivalent to a strict algebra. In seeking to extend this result to other contexts Rosicky observed a key point to be that each homotopy colimit in simplicial sets admits a decomposition into a homotopy sifted colimit of finite coproducts, and asked the author whether a similar decomposition holds in the 2-category of categories Cat. Our purpose in the present paper is to show that this is the case.Comment: Some notation changed; small amount of exposition added in intr

11 x 11 Domineering is Solved: The first player wins

We have developed a program called MUDoS (Maastricht University Domineering Solver) that solves Domineering positions in a very efficient way. This enables the solution of known positions so far (up to the 10 x 10 board) much quicker (measured in number of investigated nodes). More importantly, it enables the solution of the 11 x 11 Domineering board, a board up till now far out of reach of previous Domineering solvers. The solution needed the investigation of 259,689,994,008 nodes, using almost half a year of computation time on a single simple desktop computer. The results show that under optimal play the first player wins the 11 x 11 Domineering game, irrespective if Vertical or Horizontal starts the game. In addition, several other boards hitherto unsolved were solved. Using the convention that Vertical starts, the 8 x 15, 11 x 9, 12 x 8, 12 x 15, 14 x 8, and 17 x 6 boards are all won by Vertical, whereas the 6 x 17, 8 x 12, 9 x 11, and 11 x 10 boards are all won by Horizontal

Pattern Avoidance in Poset Permutations

We extend the concept of pattern avoidance in permutations on a totally ordered set to pattern avoidance in permutations on partially ordered sets. The number of permutations on $P$ that avoid the pattern $\pi$ is denoted $Av_P(\pi)$. We extend a proof of Simion and Schmidt to show that $Av_P(132) \leq Av_P(123)$ for any poset $P$, and we exactly classify the posets for which equality holds.Comment: 13 pages, 1 figure; v2: corrected typos; v3: corrected typos and improved formatting; v4: to appear in Order; v5: corrected typos; v6: updated author email addresse

MultiMetEval: comparative and multi-objective analysis of genome-scale metabolic models

Comparative metabolic modelling is emerging as a novel field, supported by the development of reliable and standardized approaches for constructing genome-scale metabolic models in high throughput. New software solutions are needed to allow efficient comparative analysis of multiple models in the context of multiple cellular objectives. Here, we present the user-friendly software framework Multi-Metabolic Evaluator (MultiMetEval), built upon SurreyFBA, which allows the user to compose collections of metabolic models that together can be subjected to flux balance analysis. Additionally, MultiMetEval implements functionalities for multi-objective analysis by calculating the Pareto front between two cellular objectives. Using a previously generated dataset of 38 actinobacterial genome-scale metabolic models, we show how these approaches can lead to exciting novel insights. Firstly, after incorporating several pathways for the biosynthesis of natural products into each of these models, comparative flux balance analysis predicted that species like Streptomyces that harbour the highest diversity of secondary metabolite biosynthetic gene clusters in their genomes do not necessarily have the metabolic network topology most suitable for compound overproduction. Secondly, multi-objective analysis of biomass production and natural product biosynthesis in these actinobacteria shows that the well-studied occurrence of discrete metabolic switches during the change of cellular objectives is inherent to their metabolic network architecture. Comparative and multi-objective modelling can lead to insights that could not be obtained by normal flux balance analyses. MultiMetEval provides a powerful platform that makes these analyses straightforward for biologists. Sources and binaries of MultiMetEval are freely available from https://github.com/PiotrZakrzewski/MetEv​al/downloads

Fluoromycobacteriophages for rapid, specific, and sensitive antibiotic susceptibility testing of Mycobacterium tuberculosis

Rapid antibiotic susceptibility testing of Mycobacterium tuberculosis is of paramount importance as multiple- and extensively- drug resistant strains of M. tuberculosis emerge and spread. We describe here a virus-based assay in which fluoromycobacteriophages are used to deliver a GFP or ZsYellow fluorescent marker gene to M. tuberculosis, which can then be monitored by fluorescent detection approaches including fluorescent microscopy and flow cytometry. Pre-clinical evaluations show that addition of either Rifampicin or Streptomycin at the time of phage addition obliterates fluorescence in susceptible cells but not in isogenic resistant bacteria enabling drug sensitivity determination in less than 24 hours. Detection requires no substrate addition, fewer than 100 cells can be identified, and resistant bacteria can be detected within mixed populations. Fluorescence withstands fixation by paraformaldehyde providing enhanced biosafety for testing MDR-TB and XDR-TB infections. © 2009 Piuri et al

Different reactions to adverse neighborhoods in games of cooperation

In social dilemmas, cooperation among randomly interacting individuals is often difficult to achieve. The situation changes if interactions take place in a network where the network structure jointly evolves with the behavioral strategies of the interacting individuals. In particular, cooperation can be stabilized if individuals tend to cut interaction links when facing adverse neighborhoods. Here we consider two different types of reaction to adverse neighborhoods, and all possible mixtures between these reactions. When faced with a gloomy outlook, players can either choose to cut and rewire some of their links to other individuals, or they can migrate to another location and establish new links in the new local neighborhood. We find that in general local rewiring is more favorable for the evolution of cooperation than emigration from adverse neighborhoods. Rewiring helps to maintain the diversity in the degree distribution of players and favors the spontaneous emergence of cooperative clusters. Both properties are known to favor the evolution of cooperation on networks. Interestingly, a mixture of migration and rewiring is even more favorable for the evolution of cooperation than rewiring on its own. While most models only consider a single type of reaction to adverse neighborhoods, the coexistence of several such reactions may actually be an optimal setting for the evolution of cooperation.Comment: 12 pages, 5 figures; accepted for publication in PLoS ON