Influence of a knot on the strength of a polymer strand

Many experiments have been done to determine the relative strength of different knots, and these show that the break in a knotted rope almost invariably occurs at a point just outside the `entrance' to the knot. The influence of knots on the properties of polymers has become of great interest, in part because of their effect on mechanical properties. Knot theory applied to the topology of macromolecules indicates that the simple trefoil or `overhand' knot is likely to be present with high probability in any long polymer strand. Fragments of DNA have been observed to contain such knots in experiments and computer simulations. Here we use {\it ab initio} computational methods to investigate the effect of a trefoil knot on the breaking strength of a polymer strand. We find that the knot weakens the strand significantly, and that, like a knotted rope, it breaks under tension at the entrance to the knot.Comment: 3 pages, 4 figure

Business growth, the internet and risk management in the computer games industry

According to Wasserman (2011) the growth of the Internet has transformed the software industry in a wide variety of ways. These include the creation of new business opportunities as well as significant impacts across software business processes such as software development, distribution and product support. This chapter examines one significant sub-sector of the software industry, the computer (or video) games industry, and focuses on the impact on games development companies of the opportunities created by developments in Internet and mobile technologies

Serratamolide is a hemolytic factor produced by Serratia marcescens

Serratia marcescens is a common contaminant of contact lens cases and lenses. Hemolytic factors of S. marcescens contribute to the virulence of this opportunistic bacterial pathogen. We took advantage of an observed hyper-hemolytic phenotype of crp mutants to investigate mechanisms of hemolysis. A genetic screen revealed that swrW is necessary for the hyper-hemolysis phenotype of crp mutants. The swrW gene is required for biosynthesis of the biosurfactant serratamolide, previously shown to be a broad-spectrum antibiotic and to contribute to swarming motility. Multicopy expression of swrW or mutation of the hexS transcription factor gene, a known inhibitor of swrW expression, led to an increase in hemolysis. Surfactant zones and expression from an swrW-transcriptional reporter were elevated in a crp mutant compared to the wild type. Purified serratamolide was hemolytic to sheep and murine red blood cells and cytotoxic to human airway and corneal limbal epithelial cells in vitro. The swrW gene was found in the majority of contact lens isolates tested. Genetic and biochemical analysis implicate the biosurfactant serratamolide as a hemolysin. This novel hemolysin may contribute to irritation and infections associated with contact lens use. © 2012 Shanks et al

Wide-Scale Analysis of Human Functional Transcription Factor Binding Reveals a Strong Bias towards the Transcription Start Site

We introduce a novel method to screen the promoters of a set of genes with shared biological function, against a precompiled library of motifs, and find those motifs which are statistically over-represented in the gene set. The gene sets were obtained from the functional Gene Ontology (GO) classification; for each set and motif we optimized the sequence similarity score threshold, independently for every location window (measured with respect to the TSS), taking into account the location dependent nucleotide heterogeneity along the promoters of the target genes. We performed a high throughput analysis, searching the promoters (from 200bp downstream to 1000bp upstream the TSS), of more than 8000 human and 23,000 mouse genes, for 134 functional Gene Ontology classes and for 412 known DNA motifs. When combined with binding site and location conservation between human and mouse, the method identifies with high probability functional binding sites that regulate groups of biologically related genes. We found many location-sensitive functional binding events and showed that they clustered close to the TSS. Our method and findings were put to several experimental tests. By allowing a "flexible" threshold and combining our functional class and location specific search method with conservation between human and mouse, we are able to identify reliably functional TF binding sites. This is an essential step towards constructing regulatory networks and elucidating the design principles that govern transcriptional regulation of expression. The promoter region proximal to the TSS appears to be of central importance for regulation of transcription in human and mouse, just as it is in bacteria and yeast.Comment: 31 pages, including Supplementary Information and figure

Niche as a determinant of word fate in online groups

Patterns of word use both reflect and influence a myriad of human activities and interactions. Like other entities that are reproduced and evolve, words rise or decline depending upon a complex interplay between {their intrinsic properties and the environments in which they function}. Using Internet discussion communities as model systems, we define the concept of a word niche as the relationship between the word and the characteristic features of the environments in which it is used. We develop a method to quantify two important aspects of the size of the word niche: the range of individuals using the word and the range of topics it is used to discuss. Controlling for word frequency, we show that these aspects of the word niche are strong determinants of changes in word frequency. Previous studies have already indicated that word frequency itself is a correlate of word success at historical time scales. Our analysis of changes in word frequencies over time reveals that the relative sizes of word niches are far more important than word frequencies in the dynamics of the entire vocabulary at shorter time scales, as the language adapts to new concepts and social groupings. We also distinguish endogenous versus exogenous factors as additional contributors to the fates of words, and demonstrate the force of this distinction in the rise of novel words. Our results indicate that short-term nonstationarity in word statistics is strongly driven by individual proclivities, including inclinations to provide novel information and to project a distinctive social identity.Comment: Supporting Information is available here: http://www.plosone.org/article/fetchSingleRepresentation.action?uri=info:doi/10.1371/journal.pone.0019009.s00

Making Associativity Operational

The purpose of this paper is to propose an operational idea for developing algebraic thinking in the absence of alphanumeric symbols. The paper reports on a design experiment encouraging preschool children to use the associative property algebraically. We describe the theoretical basis of the design, the tasks used, and examples of algebraic thinking in 5–6-year-old children. Theoretically, the paper makes a critical distinction between operational and structural meanings of the notion of equality. We argue that mathematical thinking involving equality among young learners can comprise both an operational and a structural conception and that the operational conception has a side that is productively linked to the structural conception. Using carefully designed hands-on tasks, the crux of the paper is the realization of algebraic thinking (in verbal mathematics) as operationally experienced in the ability to transform one number structure, with a quantity that is subject to change, into another through equality-preserving transformations

Characterization of complex networks: A survey of measurements

Each complex network (or class of networks) presents specific topological features which characterize its connectivity and highly influence the dynamics of processes executed on the network. The analysis, discrimination, and synthesis of complex networks therefore rely on the use of measurements capable of expressing the most relevant topological features. This article presents a survey of such measurements. It includes general considerations about complex network characterization, a brief review of the principal models, and the presentation of the main existing measurements. Important related issues covered in this work comprise the representation of the evolution of complex networks in terms of trajectories in several measurement spaces, the analysis of the correlations between some of the most traditional measurements, perturbation analysis, as well as the use of multivariate statistics for feature selection and network classification. Depending on the network and the analysis task one has in mind, a specific set of features may be chosen. It is hoped that the present survey will help the proper application and interpretation of measurements.Comment: A working manuscript with 78 pages, 32 figures. Suggestions of measurements for inclusion are welcomed by the author

Age-Related Comparisons of Evolution of the Inflammatory Response After Intracerebral Hemorrhage in Rats

In the hours to days after intracerebral hemorrhage (ICH), there is an inflammatory response within the brain characterized by the infiltration of peripheral neutrophils and macrophages and the activation of brain-resident microglia and astrocytes. Despite the strong correlation of aging and ICH incidence, and increasing information about cellular responses, little is known about the temporal- and age-related molecular responses of the brain after ICH. Here, we monitored a panel of 27 genes at 6 h and 1, 3, and 7 days after ICH was induced by injecting collagenase into the striatum of young adult and aged rats. Several molecules (CR3, TLR2, TLR4, IL-1β, TNFα, iNOS, IL-6) were selected to reflect the classical activation of innate immune cells (macrophages, microglia) and the potential to exacerbate inflammation and damage brain cells. Most of the others are associated with the resolution of innate inflammation, alternative pathways of macrophage/microglial activation, and the repair phase after acute injury (TGFβ, IL-1ra, IL-1r2, IL-4, IL-13, IL-4Rα, IL-13Rα1, IL-13Rα2, MRC1, ARG1, CD163, CCL22). In young animals, the up-regulation of 26 in 27 genes (not IL-4) was detected within the first week. Differences in timing or levels between young and aged animals were detected for 18 of 27 genes examined (TLR2, GFAP, IL-1β, IL-1ra, IL-1r2, iNOS, IL-6, TGFβ, MMP9, MMP12, IL-13, IL-4Rα, IL-13Rα1, IL-13Rα2, MRC1, ARG1, CD163, CCL22), with a generally less pronounced or delayed inflammatory response in the aged animals. Importantly, within this complex response to experimental ICH, the induction of pro-inflammatory, potentially harmful mediators often coincided with resolving and beneficial molecules