The clustering coefficient of a scale-free random graph

We consider a random graph process in which, at each time step, a new vertex is added with m out-neighbours, chosen with probabilities proportional to their degree plus a strictly positive constant. We show that the expectation of the clustering coefficient of the graph process is asymptotically proportional to (log n)/n. Bollobas and Riordan have previously shown that when the constant is zero, the same expectation is asymptotically proportional to ((log n)^2)/n

Improved bounds for the number of forests and acyclic orientations in the square lattice

In a recent paper Merino and Welsh (1999) studied several counting problems on the square lattice $L_n$. The authors gave the following bounds for the asymptotics of $f(n)$, the number of forests of $L_n$, and $\alpha(n)$, the number of acyclic orientations of $L_n$: $3.209912 \leq \lim_{n\rightarrow\infty} f(n)^{1/n^2} \leq 3.84161$ and $22/7 \leq \lim_{n\rightarrow\infty} \alpha(n) \leq 3.70925$. In this paper we improve these bounds as follows: $3.64497 \leq \lim_{n\rightarrow\infty} f(n)^{1/n^2} \leq 3.74101$ and $3.41358 \leq \lim_{n\rightarrow\infty} \alpha(n) \leq 3.55449$. We obtain this by developing a method for computing the Tutte polynomial of the square lattice and other related graphs based on transfer matrices

Enhanced hippocampal long-term potentiation and spatial learning in aged 11ß-hydroxysteroid dehydrogenase type 1 knock-out mice

Glucocorticoids are pivotal in the maintenance of memory and cognitive functions as well as other essential physiological processes including energy metabolism, stress responses, and cell proliferation. Normal aging in both rodents and humans is often characterized by elevated glucocorticoid levels that correlate with hippocampus-dependent memory impairments. 11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) amplifies local intracellular ("intracrine") glucocorticoid action; in the brain it is highly expressed in the hippocampus. We investigated whether the impact of 11ß-HSD1 deficiency in knock-out mice (congenic on C57BL/6J strain) on cognitive function with aging reflects direct CNS or indirect effects of altered peripheral insulin-glucose metabolism. Spatial learning and memory was enhanced in 12 month "middle-aged" and 24 month "aged" 11ß-HSD1<sup>–/–</sup> mice compared with age-matched congenic controls. These effects were not caused by alterations in other cognitive (working memory in a spontaneous alternation task) or affective domains (anxiety-related behaviors), to changes in plasma corticosterone or glucose levels, or to altered age-related pathologies in 11ß-HSD1<sup>–/–</sup> mice. Young 11ß-HSD1<sup>–/–</sup> mice showed significantly increased newborn cell proliferation in the dentate gyrus, but this was not maintained into aging. Long-term potentiation was significantly enhanced in subfield CA1 of hippocampal slices from aged 11ß-HSD1<sup>–/–</sup> mice. These data suggest that 11ß-HSD1 deficiency enhances synaptic potentiation in the aged hippocampus and this may underlie the better maintenance of learning and memory with aging, which occurs in the absence of increased neurogenesis

The art of being human : a project for general philosophy of science

Throughout the medieval and modern periods, in various sacred and secular guises, the unification of all forms of knowledge under the rubric of ‘science’ has been taken as the prerogative of humanity as a species. However, as our sense of species privilege has been called increasingly into question, so too has the very salience of ‘humanity’ and ‘science’ as general categories, let alone ones that might bear some essential relationship to each other. After showing how the ascendant Stanford School in the philosophy of science has contributed to this joint demystification of ‘humanity’ and ‘science’, I proceed on a more positive note to a conceptual framework for making sense of science as the art of being human. My understanding of ‘science’ is indebted to the red thread that runs from Christian theology through the Scientific Revolution and Enlightenment to the Humboldtian revival of the university as the site for the synthesis of knowledge as the culmination of self-development. Especially salient to this idea is science‘s epistemic capacity to manage modality (i.e. to determine the conditions under which possibilities can be actualised) and its political capacity to organize humanity into projects of universal concern. However, the challenge facing such an ideal in the twentyfirst century is that the predicate ‘human’ may be projected in three quite distinct ways, governed by what I call ‘ecological’, ‘biomedical’ and ‘cybernetic’ interests. Which one of these future humanities would claim today’s humans as proper ancestors and could these futures co-habit the same world thus become two important questions that general philosophy of science will need to address in the coming years

A natural histone H2A variant lacking the Bub1 phosphorylation site and regulated depletion of centromeric histone CENP-A foster evolvability in Candida albicans.

Eukaryotes have evolved elaborate mechanisms to ensure that chromosomes segregate with high fidelity during mitosis and meiosis, and yet specific aneuploidies can be adaptive during environmental stress. Here, we identify a chromatin-based system required for inducible aneuploidy in a human pathogen. Candida albicans utilizes chromosome missegregation to acquire tolerance to antifungal drugs and for nonmeiotic ploidy reduction after mating. We discovered that the ancestor of C. albicans and 2 related pathogens evolved a variant of histone 2A (H2A) that lacks the conserved phosphorylation site for kinetochore-associated Bub1 kinase, a key regulator of chromosome segregation. Using engineered strains, we show that the relative gene dosage of this variant versus canonical H2A controls the fidelity of chromosome segregation and the rate of acquisition of tolerance to antifungal drugs via aneuploidy. Furthermore, whole-genome chromatin precipitation analysis reveals that Centromere Protein A/ Centromeric Histone H3-like Protein (CENP-A/Cse4), a centromeric histone H3 variant that forms the platform of the eukaryotic kinetochore, is depleted from tetraploid-mating products relative to diploid parents and is virtually eliminated from cells exposed to aneuploidy-promoting cues. We conclude that genetically programmed and environmentally induced changes in chromatin can confer the capacity for enhanced evolvability via chromosome missegregation

Dynamic interfacial trapping of flexural waves in structured plates

The paper presents new results on the localization and transmission of flexural waves in a structured plate containing a semi-infinite two-dimensional array of rigid pins. In particular, localized waves are identified and studied at the interface boundary between the homogeneous part of the flexural plate and the part occupied by rigid pins. A formal connection has been made with the dispersion properties of flexural Bloch waves in an infinite doubly periodic array of rigid pins. Special attention is given to regimes corresponding to standing waves of different types as well as Dirac-like points that may occur on the dispersion surfaces. A single half-grating problem, hitherto unreported in the literature, is also shown to bring interesting solutions

The place of strategic environmental assessment in the privatised electricity industry

The private sector has given relatively little attention to the emergence of strategic environmental assessment (SEA); even recently privatised utilities, where SEA might be deemed particularly appropriate, and whose activities are likely to fall within the scope of the European Union SEA Directive, have shown less interest than might be expected. However, the global trend towards the privatisation of state-owned enterprises makes the adaptation of SEA towards these industries all the more pressing. This paper addresses the place that SEA might take within the electricity sector, taking the privatised UK electricity industry as an example. Particular challenges are posed by the radical restructuring of the industry, designed to introduce competitive behaviour, making the development of comprehensive SEA processes problematic, and requiring SEA to be placed in the context of corporate environmental policy and objectives.</p

Stimulation of shrimp (Penaeus monodon) hemocytes by lipopolysaccharide-like molecules derived from Novacq™

Immune stimulation through feed additives is a promising strategy that can help to combat disease in shrimp farming and reduce the use of antibiotics and other chemotherapeutics. The present study investigated the in vitro immunostimulatory effects of lipopolysaccharide (LPS)-like molecules isolated from the microbial based feed additive Novacq™ (N-LPS). The presence of LPS-like molecules was confirmed and quantified Novacq™ using a HEK-TLR4 reporter cell line. Primary hemocytes isolated from adult Penaeus monodon were used to measure the immunostimulatory of N-LPS compared with the control group that were treated with E. coli derived LPS (E-LPS). The N-LPS stimulated a rapid and significant induction of the phenoloxidase (PO) response in the hemocytes. The PO response increased with exposure time and LPS concentration and was significantly higher compared with an E. coli LPS (E-LPS) control. In addition, using gene expression data, we quantified the transcriptome response of the hemocytes at 15, 30 and 60 mins post stimulation. Compared with the controls, the N-LPS treated hemocytes had a significant up-regulation of genes involved in the immune system modulation and control at all time-points. Most noteworthy was the significant induction of transcripts that function as serine protease inhibitors (namely SERPINs), that regulate the overexpression of the PO system. Transcription factors from the Notch family which directly regulate the expression of many immune genes were also induced within the hemocytes. Additionally, we also saw a strong up-regulation of crustacean hyperglycemic hormone (CHH) transcripts, an important neuropeptide involved in immune function. Overall, the transcriptome profile of the hemocytes suggests that the LPS component of Novacq™ is highly immunostimulatory and generates a strong PO response in vitro. The subsequent transcriptional response appears to be directed towards preventing further activation of the PO system most likely in an attempt to limit cytoxicity to the host. Our study highlights the immunostimulatory ability of Novacq™ and provides further evidence of the positive health benefits this microbial based feed additive can have in shrimp.</p

Advance telephone calls ahead of reminder questionnaires increase response rate in non-responders compared to questionnaire reminders only : The RECORD phone trial

Peer reviewedPublisher PD