Effects of poloidal sheared flow and active feedback on tokamak edge fluctuations

The influence of sheared poloidal flow and of a phase sensitive feedback source on the various edge instabilities of tokamaks are investigated. The conditions for stabilization of the rippling mode, for the drift dissipative mode and for the radiative condensation instability are obtained from detailed numerical solutions and from approximate analytic solutions of the relevant eigenmode equations

Phosphoenolpyruvate carboxylase dentified as a key enzyme in erythrocytic Plasmodium falciparum carbon metabolism

Phospoenolpyruvate carboxylase (PEPC) is absent from humans but encoded in thePlasmodium falciparum genome, suggesting that PEPC has a parasite-specific function. To investigate its importance in P. falciparum, we generated a pepc null mutant (D10Δpepc), which was only achievable when malate, a reduction product of oxaloacetate, was added to the growth medium. D10Δpepc had a severe growth defect in vitro, which was partially reversed by addition of malate or fumarate, suggesting that pepc may be essential in vivo. Targeted metabolomics using 13C-U-D-glucose and 13C-bicarbonate showed that the conversion of glycolytically-derived PEP into malate, fumarate, aspartate and citrate was abolished in D10Δpepc and that pentose phosphate pathway metabolites and glycerol 3-phosphate were present at increased levels. In contrast, metabolism of the carbon skeleton of 13C,15N-U-glutamine was similar in both parasite lines, although the flux was lower in D10Δpepc; it also confirmed the operation of a complete forward TCA cycle in the wild type parasite. Overall, these data confirm the CO2 fixing activity of PEPC and suggest that it provides metabolites essential for TCA cycle anaplerosis and the maintenance of cytosolic and mitochondrial redox balance. Moreover, these findings imply that PEPC may be an exploitable target for future drug discovery

Chimera-like states in modular neural networks

Chimera states, namely the coexistence of coherent and incoherent behavior, were previously analyzed in complex networks. However, they have not been extensively studied in modular networks. Here, we consider a neural network inspired by the connectome of the C. elegans soil worm, organized into six interconnected communities, where neurons obey chaotic bursting dynamics. Neurons are assumed to be connected with electrical synapses within their communities and with chemical synapses across them. As our numerical simulations reveal, the coaction of these two types of coupling can shape the dynamics in such a way that chimera-like states can happen. They consist of a fraction of synchronized neurons which belong to the larger communities, and a fraction of desynchronized neurons which are part of smaller communities. In addition to the Kuramoto order parameter ?, we also employ other measures of coherence, such as the chimera-like ? and metastability ? indices, which quantify the degree of synchronization among communities and along time, respectively. We perform the same analysis for networks that share common features with the C. elegans neural network. Similar results suggest that under certain assumptions, chimera-like states are prominent phenomena in modular networks, and might provide insight for the behavior of more complex modular networks

Centrifugal melt spinning of polyvinylpyrrolidone (PVP)/triacontene copolymer fibres

Polyvinylpyrrolidone/1-triacontene (PVP/TA) copolymer fibre webs produced by centrifugal melt spinning were studied to determine the influence of jet rotation speed on morphology and internal structure as well as their potential utility as adsorbent capture media for disperse dye effluents. Fibres were produced at 72 C with jet head rotation speeds from 7000 to 15,000 r min-1. The fibres were characterised by means of SEM, XRD and DSC. Adsorption behaviour was investigated by means of an isothermal bottle point adsorption study using a commercial disperse dye, Dianix AC-E. Through centrifugal spinning nanofibers and microfibers could be produced with individual fibres as fine as 200–300 nm and mean fibre diameters of ca. 1–2 lm. The PVP/TA fibres were mechanically brittle with characteristic brittle tensile fracture regions observed at the fibre ends. DSC and XRD analyses suggested that this brittleness was linked to the graft chain crystallisation where the PVP/TA was in the form of a radial brush copolymer. In this structure, the triacontene branches interlock and form small lateral crystals around an amorphous backbone. As an adsorbent, the PVP/TA fibres were found to adsorb 35.4 mg g-1 compared to a benchmark figure of 30.0 mg g-1 for a granular-activated carbon adsorbent under the same application conditions. PVP/TA is highly hydrophobic and adsorbs disperse dyes through the strong ‘‘hydrophobic bonding’’ interaction. Such fibrous assemblies may have applications in the targeted adsorption and separation of non-polar species from aqueous or polar environments

Sparse Gamma Rhythms Arising through Clustering in Adapting Neuronal Networks

Gamma rhythms (30–100 Hz) are an extensively studied synchronous brain state responsible for a number of sensory, memory, and motor processes. Experimental evidence suggests that fast-spiking interneurons are responsible for carrying the high frequency components of the rhythm, while regular-spiking pyramidal neurons fire sparsely. We propose that a combination of spike frequency adaptation and global inhibition may be responsible for this behavior. Excitatory neurons form several clusters that fire every few cycles of the fast oscillation. This is first shown in a detailed biophysical network model and then analyzed thoroughly in an idealized model. We exploit the fact that the timescale of adaptation is much slower than that of the other variables. Singular perturbation theory is used to derive an approximate periodic solution for a single spiking unit. This is then used to predict the relationship between the number of clusters arising spontaneously in the network as it relates to the adaptation time constant. We compare this to a complementary analysis that employs a weak coupling assumption to predict the first Fourier mode to destabilize from the incoherent state of an associated phase model as the external noise is reduced. Both approaches predict the same scaling of cluster number with respect to the adaptation time constant, which is corroborated in numerical simulations of the full system. Thus, we develop several testable predictions regarding the formation and characteristics of gamma rhythms with sparsely firing excitatory neurons

DESNT: A Poor Prognosis Category of Human Prostate Cancer.

BACKGROUND: A critical problem in the clinical management of prostate cancer is that it is highly heterogeneous. Accurate prediction of individual cancer behaviour is therefore not achievable at the time of diagnosis leading to substantial overtreatment. It remains an enigma that, in contrast to breast cancer, unsupervised analyses of global expression profiles have not currently defined robust categories of prostate cancer with distinct clinical outcomes. OBJECTIVE: To devise a novel classification framework for human prostate cancer based on unsupervised mathematical approaches. DESIGN, SETTING, AND PARTICIPANTS: Our analyses are based on the hypothesis that previous attempts to classify prostate cancer have been unsuccessful because individual samples of prostate cancer frequently have heterogeneous compositions. To address this issue, we applied an unsupervised Bayesian procedure called Latent Process Decomposition to four independent prostate cancer transcriptome datasets obtained using samples from prostatectomy patients and containing between 78 and 182 participants. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Biochemical failure was assessed using log-rank analysis and Cox regression analysis. RESULTS AND LIMITATIONS: Application of Latent Process Decomposition identified a common process in all four independent datasets examined. Cancers assigned to this process (designated DESNT cancers) are characterized by low expression of a core set of 45 genes, many encoding proteins involved in the cytoskeleton machinery, ion transport, and cell adhesion. For the three datasets with linked prostate-specific antigen failure data following prostatectomy, patients with DESNT cancer exhibited poor outcome relative to other patients (p=2.65×10-5, p=4.28×10-5, and p=2.98×10-8). When these three datasets were combined the independent predictive value of DESNT membership was p=1.61×10-7 compared with p=1.00×10-5 for Gleason sum. A limitation of the study is that only prediction of prostate-specific antigen failure was examined. CONCLUSIONS: Our results demonstrate the existence of a novel poor prognosis category of human prostate cancer and will assist in the targeting of therapy, helping avoid treatment-associated morbidity in men with indolent disease. PATIENT SUMMARY: Prostate cancer, unlike breast cancer, does not have a robust classification framework. We propose that this failure has occurred because prostate cancer samples selected for analysis frequently have heterozygous compositions (individual samples are made up of many different parts that each have different characteristics). Applying a mathematical approach that can overcome this problem we identify a novel poor prognosis category of human prostate cancer called DESNT.This work was funded by the Bob Champion Cancer Trust, The Masonic Charitable Foundation successor to The Grand Charity, The King Family, and The University of East Anglia. We acknowledge support from Movember, from Prostate Cancer UK, Callum Barton, and from The Andy Ripley Memorial Fund. The research presented in this paper was carried out on the High Performance Computing Cluster supported by the Research and Specialist Computing Support service at the University of East Anglia. Cancer Research UK Grant 10047 funded the generation of the prostate CancerMap expression microarray dataset. We would like to acknowledge the support of the National Institute for Health Research which funds the Cambridge Bio-medical Research Centre, Cambridge UK

An Empirical Comparison of Consumer Innovation Adoption Models: Implications for Subsistence Marketplaces

So called “pro-poor” innovations may improve consumer wellbeing in subsistence marketplaces. However, there is little research that integrates the area with the vast literature on innovation adoption. Using a questionnaire where respondents were asked to provide their evaluations about a mobile banking innovation, this research fills this gap by providing empirical evidence of the applicability of existing innovation adoption models in subsistence marketplaces. The study was conducted in Bangladesh among a geographically dispersed sample. The data collected allowed an empirical comparison of models in a subsistence context. The research reveals the most useful models in this context to be the Value Based Adoption Model and the Consumer Acceptance of Technology model. In light of these findings and further examination of the model comparison results the research also shows that consumers in subsistence marketplaces are not just motivated by functionality and economic needs. If organizations cannot enhance the hedonic attributes of a pro-poor innovation, and reduce the internal/external constraints related to adoption of that pro-poor innovation, then adoption intention by consumers will be lower

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio