On pairwise distances and median score of three genomes under DCJ

In comparative genomics, the rearrangement distance between two genomes (equal the minimal number of genome rearrangements required to transform them into a single genome) is often used for measuring their evolutionary remoteness. Generalization of this measure to three genomes is known as the median score (while a resulting genome is called median genome). In contrast to the rearrangement distance between two genomes which can be computed in linear time, computing the median score for three genomes is NP-hard. This inspires a quest for simpler and faster approximations for the median score, the most natural of which appears to be the halved sum of pairwise distances which in fact represents a lower bound for the median score. In this work, we study relationship and interplay of pairwise distances between three genomes and their median score under the model of Double-Cut-and-Join (DCJ) rearrangements. Most remarkably we show that while a rearrangement may change the sum of pairwise distances by at most 2 (and thus change the lower bound by at most 1), even the most "powerful" rearrangements in this respect that increase the lower bound by 1 (by moving one genome farther away from each of the other two genomes), which we call strong, do not necessarily affect the median score. This observation implies that the two measures are not as well-correlated as one's intuition may suggest. We further prove that the median score attains the lower bound exactly on the triples of genomes that can be obtained from a single genome with strong rearrangements. While the sum of pairwise distances with the factor 2/3 represents an upper bound for the median score, its tightness remains unclear. Nonetheless, we show that the difference of the median score and its lower bound is not bounded by a constant.Comment: Proceedings of the 10-th Annual RECOMB Satellite Workshop on Comparative Genomics (RECOMB-CG), 2012. (to appear

Isolation, phenotype, and allostimulatory activity of mouse liver dendritic cells

Donor liver-derived dendritic cells (DC) have recently been identified within various lymphoid and nonlymphoid tissues of organ allograft recipients, including nonimmunosuppressed mice transplanted with and permanently accepting major histocompatibility complex (MHC)-disparate hepatic allografts. These findings have raised questions about the basis of the tolerogenicity of the liver—and, in particular, about the properties of liver-derived DC. To study further the structure, immunophenotype and allostimu-latory activity of leukocytes resident in normal mouse (B10.BR; H-2k, I-Ek) liver, a procedure was developed to maximize the yield of viable, nonparenchymal cells (NPC) obtained following collagenase digestion of perfused liver fragments and density centrifugation (Per-coll). These cells comprised populations expressing lymphoid and myeloid cell surface antigens. As compared with spleen cells, they proved good allostimula-tors of naive (BIO; H-2b, I-E") splenic T cells when tested in primary mixed leukocyte reactions (MLR). After overnight (18-hr) incubation of the NPC, enrichment for transiently adherent, low-density (LD) cells on metrizamide gradients permitted the recovery of low numbers of cells (approx. 2-5 × 105 per liver), many of which displayed distinct DC morphology. Flow cytometric analysis revealed that these cells were CD3-, CD4-, CD8-, and B220-, but strongly expressed CD45 (leukocyte-common antigen), and mild-to-moderate levels of CD lib, heat-stable antigen, and CD44. The cells also expressed moderate intensity of NLDC 145 but not 33D1, DC restricted markers which have been shown to be differentially expressed on mouse DC isolated from various organs. This DC-enriched population was more strongly MHC class II(I-Ek)+ than NPC, as determined by immunocytochemistry and flow cytometry and exhibited much more potent allo-stimulatory activity for naive T cells. These findings demonstrate that freshly isolated murine liver NPC, and perhaps their counterparts in situ, exhibit allo-stimulatory activity that is enhanced in the nonadherent, low-density (DC-enriched) fraction after overnight culture. They further suggest that the © 1994 by Williams and Wilkins

HIV infection and domestic smoke exposure, but not human papillomavirus, are risk factors for esophageal squamous cell carcinoma in Zambia: a case-control study

(c) 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

A systematic review of ICD complications in randomised controlled trials versus registries: is our 'real-world' data an underestimation?

Implantable cardioverter defibrillator (ICD) implantation carries a significant risk of complications, however published estimates appear inconsistent. We aimed to present a contemporary systematic review using meta-analysis methods of ICD complications in randomised controlled trials (RCTs) and compare it to recent data from the largest international ICD registry, the US National Cardiovascular Data Registry (NCDR). PubMed was searched for any RCTs involving ICD implantation published 1999-2013; 18 were identified for analysis including 6433 patients, mean follow-up 3 months-5.6 years. Exclusion criteria were studies of children, hypertrophic cardiomyopathy, congenital heart disease, resynchronisation therapy and generator changes. Total pooled complication rate from the RCTs (excluding inappropriate shocks) was 9.1%, including displacement 3.1%, pneumothorax 1.1% and haematoma 1.2%. Infection rate was 1.5%.There were no predictors of complications but longer follow-up showed a trend to higher complication rates (p=0.07). In contrast, data from the NCDR ICD, reporting on 356 515 implants (2006-2010) showed a statistically significant threefold lower total major complication rate of 3.08% with lead displacement 1.02%, haematoma 0.86% and pneumothorax 0.44%. The overall ICD complication rate in our meta-analysis is 9.1% over 16 months. The ICD complication reported in the NCDR ICD registry is significantly lower despite a similar population. This may reflect under-reporting of complications in registries. Reporting of ICD complications in RCTs and registries is very variable and there is a need to standardise classification of complications internationally

A path-integral approach to polynomial invariants of links

A brief review of a self-contained genuinely three-dimensional monodromy-matrix based non-perturbative covariant path-integral approach to {\it polynomial invariants} of knots and links in the framework of (topological) quantum Chern-Simons field theory is given. An idea of ``physical'' observables represented by an auxiliary topological quantum-mechanics model in an external gauge field is introduced substituting rather a limited notion of the Wilson loop. Thus, the possibility of using various generalizations of the Chern-Simons action (also higher-dimensional ones) as well as a purely functional language becomes open. The theory is quantized in the framework of the best suited in this case {\it antibracket-antifield} formalism of Batalin and Vilkovisky. Using the Stokes theorem and formal translational invariance of the path-integral measure a {\it monodromy matrix} corresponding to an arbitrary pair of irreducible representations of an arbitrary semi-simple Lie group is derived

Creative benefits from well-connected leaders? Leader social network ties as facilitators of employee radical creativity

Employee radical creativity critically depends on substantive informational resources from others across the wider organization. We propose that the social network ties of employees’ immediate leaders assume a central role in garnering these resources, thereby fostering their employees’ radical creativity both independent of and interactively with employees’ own network ties. Drawing on data from 214 employees working in 30 teams of a public technology and environmental services organization, we find that team leaders’ betweenness centrality in the idea network within their teams as well as among their peer leaders provides creative benefits beyond employees’ own internal and external ties. Further, employees’ and leaders’ ties within and external to the team interactively predict employee radical creativity. Implications for theory and practice are discusse

A New Method for Producing Pharmaceutical Co-crystals: Laser Irradiation of Powder Blends

In this work, a high-power CO2 laser was used to irradiate powder blends of co-crystal formers, with the specific aim of trying to cause recrystallization to a co-crystal structure. By varying the power and raster speed of the laser, it was found that sufficient thermal energy could be imparted to the powder to cause molecular rearrangement. It was possible to form co-crystals of caffeine with oxalic acid and caffeine with malonic acid. Interestingly, it was found that, to form co-crystals successfully, the coformers needed to sublime to an appreciable extent, which indicates that the mechanism of rearrangement involves interaction and nucleation in the vapor phase. Laser irradiation thus offers a new route to creation of pharmaceutical co-crystals and a potentially rapid screen for likely co-crystal formation between coforming pairs

An implementation of Deflate in Coq

The widely-used compression format "Deflate" is defined in RFC 1951 and is based on prefix-free codings and backreferences. There are unclear points about the way these codings are specified, and several sources for confusion in the standard. We tried to fix this problem by giving a rigorous mathematical specification, which we formalized in Coq. We produced a verified implementation in Coq which achieves competitive performance on inputs of several megabytes. In this paper we present the several parts of our implementation: a fully verified implementation of canonical prefix-free codings, which can be used in other compression formats as well, and an elegant formalism for specifying sophisticated formats, which we used to implement both a compression and decompression algorithm in Coq which we formally prove inverse to each other -- the first time this has been achieved to our knowledge. The compatibility to other Deflate implementations can be shown empirically. We furthermore discuss some of the difficulties, specifically regarding memory and runtime requirements, and our approaches to overcome them

Laser irradiation to produce amorphous pharmaceuticals

Using a high-power CO2 laser to irradiate powder beds, it was possible to induce phase transformation to the amorphous state. Irradiation of a model drug, indometacin, resulted in formation of a glass. Varying the settings of the laser (power and raster speed) was shown to change the physicochemical properties of the glasses produced and all irradiated glasses were found to be more stable than a reference glass produced by melt-quenching. Irradiation of a powder blend of paracetamol and polyvinylpyrrolidone K30 was found to produce a solid amorphous dispersion. The results suggest that laser-irradiation might be a useful method for making amorphous pharmaceuticals