Thermodynamical Metrics and Black Hole Phase Transitions

An important phase transition in black hole thermodynamics is associated with the divergence of the specific heat with fixed charge and angular momenta, yet one can demonstrate that neither Ruppeiner's entropy metric nor Weinhold's energy metric reveals this phase transition. In this paper, we introduce a new thermodynamical metric based on the Hessian matrix of several free energy. We demonstrate, by studying various charged and rotating black holes, that the divergence of the specific heat corresponds to the curvature singularity of this new metric. We further investigate metrics on all thermodynamical potentials generated by Legendre transformations and study correspondences between curvature singularities and phase transition signals. We show in general that for a system with n-pairs of intensive/extensive variables, all thermodynamical potential metrics can be embedded into a flat (n,n)-dimensional space. We also generalize the Ruppeiner metrics and they are all conformal to the metrics constructed from the relevant thermodynamical potentials.Comment: Latex, 25 pages, reference added, typos corrected, English polished and the Hawking-Page phase transition clarified; to appear in JHE

Effects of bowel preparation on intestinal bacterial associated urine and faecal metabolites and the associated faecal microbiome

Background Urinary and faecal metabolic profiling have been extensively studied in gastrointestinal diseases as potential diagnostic markers, and to enhance our understanding of the intestinal microbiome in the pathogenesis these conditions. The impact of bowel cleansing on the microbiome has been investigated in several studies, but limited to just one study on the faecal metabolome. Aim To compare the effects of bowel cleansing on the composition of the faecal microbiome, and the urine and faecal metabolome. Methods Urine and faecal samples were obtained from eleven patients undergoing colonoscopy at baseline, and then at day 3 and week 6 after colonoscopy. 16S rRNA gene sequencing was used to analyse changes in the microbiome, and metabonomic analysis was performed using proton nuclear magnetic resonance (1H NMR) spectroscopy. Results Microbiomic analysis demonstrated a reduction in alpha diversity (Shannon index) between samples taken at baseline and three days following bowel cleansing (p = 0.002), and there was no significant difference between samples at baseline and six weeks post colonoscopy. Targeted and non-targeted analysis of urinary and faecal bacterial associated metabolites showed no significant impact following bowel cleansing. Conclusions Bowel cleansing causes a temporary disturbance in bacterial alpha diversity measured in faeces, but no significant changes in the faecal and urine metabolic profiles, suggesting that overall the faecal microbiome and its associated metabolome is resistant to the effects of an induced osmotic diarrhoea

Conservation genomics reveals possible illegal trade routes and admixture across pangolin lineages in Southeast Asia

The use of genome-wide genetic markers is an emerging approach for informing evidence-based management decisions for highly threatened species. Pangolins are the most heavily trafficked mammals across illegal wildlife trade globally, but critically endangered Sunda pangolins (Manis javanica) have not been widely studied in insular Southeast Asia. We used > 12,000 single nucleotide polymorphic markers (SNPs) to assign pangolin seizures from illegal trade of unknown origin to possible geographic sources via genetic clustering with pangolins of known origin. Our SNPs reveal three previously unrecognized genetic lineages of Sunda pangolins, possibly from Borneo, Java and Singapore/Sumatra. The seizure assignments suggest the majority of pangolins were traded from Borneo to Java. Using mitochondrial markers did not provide the same resolution of pangolin lineages, and to explore if admixture might explain these differences, we applied sophisticated tests of introgression using > 2000 SNPs to investigate secondary gene flow between each of the three Sunda pangolin lineages. It is possible the admixture which we discovered is due to human-mediated movements of pangolins. Our findings impact a range of conservation actions, including tracing patterns of trade, repatriation of rescue animals, and conservation breeding. In order to conserve genetic diversity, we suggest that, pending further research, each pangolin lineage should as a precaution be protected and managed as an evolutionarily distinct conservation unit

Human Computation and Convergence

Humans are the most effective integrators and producers of information, directly and through the use of information-processing inventions. As these inventions become increasingly sophisticated, the substantive role of humans in processing information will tend toward capabilities that derive from our most complex cognitive processes, e.g., abstraction, creativity, and applied world knowledge. Through the advancement of human computation - methods that leverage the respective strengths of humans and machines in distributed information-processing systems - formerly discrete processes will combine synergistically into increasingly integrated and complex information processing systems. These new, collective systems will exhibit an unprecedented degree of predictive accuracy in modeling physical and techno-social processes, and may ultimately coalesce into a single unified predictive organism, with the capacity to address societies most wicked problems and achieve planetary homeostasis.Comment: Pre-publication draft of chapter. 24 pages, 3 figures; added references to page 1 and 3, and corrected typ

Synergistic Inhibition of Endothelial Cell Proliferation, Tube Formation, and Sprouting by Cyclosporin A and Itraconazole

Pathological angiogenesis contributes to a number of diseases including cancer and macular degeneration. Although angiogenesis inhibitors are available in the clinic, their efficacy against most cancers is modest due in part to the existence of alternative and compensatory signaling pathways. Given that angiogenesis is dependent on multiple growth factors and a broad signaling network in vivo, we sought to explore the potential of multidrug cocktails for angiogenesis inhibition. We have screened 741 clinical drug combinations for the synergistic inhibition of endothelial cell proliferation. We focused specifically on existing clinical drugs since the re-purposing of clinical drugs allows for a more rapid and cost effective transition to clinical studies when compared to new drug entities. Our screen identified cyclosporin A (CsA), an immunosuppressant, and itraconazole, an antifungal drug, as a synergistic pair of inhibitors of endothelial cell proliferation. In combination, the IC50 dose of each drug is reduced by 3 to 9 fold. We also tested the ability of the combination to inhibit endothelial cell tube formation and sprouting, which are dependent on two essential processes in angiogenesis, endothelial cell migration and differentiation. We found that CsA and itraconazole synergistically inhibit tube network size and sprout formation. Lastly, we tested the combination on human foreskin fibroblast viability as well as Jurkat T cell and HeLa cell proliferation, and found that endothelial cells are selectively targeted. Thus, it is possible to combine existing clinical drugs to synergistically inhibit in vitro models of angiogenesis. This strategy may be useful in pursuing the next generation of antiangiogenesis therapy

Modular and predictable assembly of porous organic molecular crystals

Nanoporous molecular frameworks are important in applications such as separation, storage and catalysis. Empirical rules exist for their assembly but it is still challenging to place and segregate functionality in three-dimensional porous solids in a predictable way. Indeed, recent studies of mixed crystalline frameworks suggest a preference for the statistical distribution of functionalities throughout the pores rather than, for example, the functional group localization found in the reactive sites of enzymes. This is a potential limitation for 'one-pot' chemical syntheses of porous frameworks from simple starting materials. An alternative strategy is to prepare porous solids from synthetically preorganized molecular pores. In principle, functional organic pore modules could be covalently prefabricated and then assembled to produce materials with specific properties. However, this vision of mix-and-match assembly is far from being realized, not least because of the challenge in reliably predicting three-dimensional structures for molecular crystals, which lack the strong directional bonding found in networks. Here we show that highly porous crystalline solids can be produced by mixing different organic cage modules that self-assemble by means of chiral recognition. The structures of the resulting materials can be predicted computationally, allowing in silico materials design strategies. The constituent pore modules are synthesized in high yields on gram scales in a one-step reaction. Assembly of the porous co-crystals is as simple as combining the modules in solution and removing the solvent. In some cases, the chiral recognition between modules can be exploited to produce porous organic nanoparticles. We show that the method is valid for four different cage modules and can in principle be generalized in a computationally predictable manner based on a lock-and-key assembly between modules

Narratives for drug design

We explore the role of narratives of complex systems in anti-cancer drug design. We set out the value of narratives relating to cancer in promoting awareness of risky behaviour and in supporting decision-making regarding treatment options. We present cancer as a dysregulated, complex system that has emergent behaviours at multiple scales, and is governed by dynamical spatio-temporal processes. We show that this system changes structure and function in response to anti-cancer drugs, and explain that these changes are sufficiently complex to impede effective drug design. We pose what narrative might offer to support the process of drug design, providing an example of work done to date that might serve as a foundation for narrating complexity. We suggest ways of using this work combined with that of others to begin to consider narrating drug design

Small Horizons

All near horizon geometries of supersymmetric black holes in a N=2, D=5 higher-derivative supergravity theory are classified. Depending on the choice of near-horizon data we find that either there are no regular horizons, or horizons exist and the spatial cross-sections of the event horizons are conformal to a squashed or round S^3, S^1 * S^2, or T^3. If the conformal factor is constant then the solutions are maximally supersymmetric. If the conformal factor is not constant, we find that it satisfies a non-linear vortex equation, and the horizon may admit scalar hair.Comment: 21 pages, latex. Typos corrected and reference adde

Author correction: High-resolution bacterial 16S rRNA gene profile meta-analysis and biofilm status reveal common colorectal cancer consortia

In this Article, in the section entitled ‘Quantitative real-time PCR’ within the Supplementary Methods, the probe for the Bacteroides fragilis 16S real-time PCR reaction was listed incorrectly as 5ʹHEX-AGGGACTGGAAGGCTTTACTGCTTC-3ʹBHQ1. The correct probe for Bacteroides fragilis 16S should be listed as 5ʹHEX-ACACGTATCCAACCTGCCCTTTACTCG-3ʹBHQ1. The mistake was a result of a copy and paste error with a different primer set targeting a B. fragilis toxin gene. All qPCR reactions were performed using the correct probe, and therefore no data were affected