Holographic Wilsonian flows and emergent fermions in extremal charged black holes

We study holographic Wilsonian RG in a general class of asymptotically AdS backgrounds with a U(1) gauge field. We consider free charged Dirac fermions in such a background, and integrate them up to an intermediate radial distance, yielding an equivalent low energy dual field theory. The new ingredient, compared to scalars, involves a `generalized' basis of coherent states which labels a particular half of the fermion components as coordinates or momenta, depending on the choice of quantization (standard or alternative). We apply this technology to explicitly compute RG flows of charged fermionic operators and their composites (double trace operators) in field theories dual to (a) pure AdS and (b) extremal charged black hole geometries. The flow diagrams and fixed points are determined explicitly. In the case of the extremal black hole, the RG flows connect two fixed points at the UV AdS boundary to two fixed points at the IR AdS_2 region. The double trace flow is shown, both numerically and analytically, to develop a pole singularity in the AdS_2 region at low frequency and near the Fermi momentum, which can be traced to the appearance of massless fermion modes on the low energy cut-off surface. The low energy field theory action we derive exactly agrees with the semi-holographic action proposed by Faulkner and Polchinski in arXiv:1001.5049 [hep-th]. In terms of field theory, the holographic version of Wilsonian RG leads to a quantum theory with random sources. In the extremal black hole background the random sources become `light' in the AdS_2 region near the Fermi surface and emerge as new dynamical degrees of freedom.Comment: 37 pages (including 8 pages of appendix), 10 figures and 2 table

Simple, Fast and Accurate Implementation of the Diffusion Approximation Algorithm for Stochastic Ion Channels with Multiple States

The phenomena that emerge from the interaction of the stochastic opening and closing of ion channels (channel noise) with the non-linear neural dynamics are essential to our understanding of the operation of the nervous system. The effects that channel noise can have on neural dynamics are generally studied using numerical simulations of stochastic models. Algorithms based on discrete Markov Chains (MC) seem to be the most reliable and trustworthy, but even optimized algorithms come with a non-negligible computational cost. Diffusion Approximation (DA) methods use Stochastic Differential Equations (SDE) to approximate the behavior of a number of MCs, considerably speeding up simulation times. However, model comparisons have suggested that DA methods did not lead to the same results as in MC modeling in terms of channel noise statistics and effects on excitability. Recently, it was shown that the difference arose because MCs were modeled with coupled activation subunits, while the DA was modeled using uncoupled activation subunits. Implementations of DA with coupled subunits, in the context of a specific kinetic scheme, yielded similar results to MC. However, it remained unclear how to generalize these implementations to different kinetic schemes, or whether they were faster than MC algorithms. Additionally, a steady state approximation was used for the stochastic terms, which, as we show here, can introduce significant inaccuracies. We derived the SDE explicitly for any given ion channel kinetic scheme. The resulting generic equations were surprisingly simple and interpretable - allowing an easy and efficient DA implementation. The algorithm was tested in a voltage clamp simulation and in two different current clamp simulations, yielding the same results as MC modeling. Also, the simulation efficiency of this DA method demonstrated considerable superiority over MC methods.Comment: 32 text pages, 10 figures, 1 supplementary text + figur

Widespread platinum anomaly documented at theYounger Dryas onset in North American sedimentary sequences

Previously, a large platinum (Pt) anomaly was reported in the Greenland ice sheet at the Younger Dryas boundary (YDB) (12,800 Cal B.P.). In order to evaluate its geographic extent, fire-assay and inductively coupled plasma mass spectrometry (FA and ICP-MS) elemental analyses were performed on 11 widely separated archaeological bulk sedimentary sequences. We document discovery of a distinct Pt anomaly spread widely across North America and dating to the Younger Dryas (YD) onset. The apparent synchroneity of this widespread YDB Pt anomaly is consistent with Greenland Ice Sheet Project 2 (GISP2) data that indicated atmospheric input of platinum-rich dust. We expect the Pt anomaly to serve as a widely-distributed time marker horizon (datum) for identification and correlation of the onset of the YD climatic episode at 12,800 Cal B.P. This Pt datum will facilitate the dating and correlating of archaeological, paleontological, and paleoenvironmental data between sequences, especially those with limited age control

Phenotypic Variation and Bistable Switching in Bacteria

Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.

Heterogeneity of ubiquitin pathology in frontotemporal lobar degeneration: classification and relation to clinical phenotype

We have investigated the extent and pattern of immunostaining for ubiquitin protein (UBQ) in 60 patients with frontotemporal lobar degeneration (FTLD) with ubiquitin-positive, tau-negative inclusions (FTLD-U), 37 of whom were ascertained in Manchester UK and 23 in Newcastle-Upon-Tyne, UK. There were three distinct histological patterns according to the form and distribution of the UBQ pathology. Histological type 1 was present in 19 patients (32%) and characterised by the presence of a moderate number, or numerous, UBQ immunoreactive neurites and intraneuronal cytoplasmic inclusions within layer II of the frontal and temporal cerebral cortex, and cytoplasmic inclusions within granule cells of the dentate gyrus; neuronal intranuclear inclusions (NII) of a “cat’s eye” or “lentiform” appearance were present in 17 of these patients. In histological type 2 (16 patients, 27%), UBQ neurites were predominantly, or exclusively, present with few intraneuronal cytoplasmic inclusions within layer II of the cerebral cortex, while in histological type 3 (25 patients, 42%), UBQ intraneuronal cytoplasmic inclusions either within the cortical layer II or in the granule cells of the dentate gyrus, with few or no UBQ neurites, were seen. In neither of these latter two groups were NII present. The influence of histological type on clinical phenotype was highly significant with type 1 histology being associated clinically with cases of frontotemporal dementia (FTD) or progressive non-fluent aphasia (PNFA), type 2 histology with semantic dementia (SD), and type 3 histology with FTD, or FTD and motor neurone disease (MND)

Self-Reactivities to the Non-Erythroid Alpha Spectrin Correlate with Cerebral Malaria in Gabonese Children

BACKGROUND: Hypergammaglobulinemia and polyclonal B-cell activation commonly occur in Plasmodium sp. infections. Some of the antibodies produced recognize self-components and are correlated with disease severity in P. falciparum malaria. However, it is not known whether some self-reactive antibodies produced during P. falciparum infection contribute to the events leading to cerebral malaria (CM). We show here a correlation between self-antibody responses to a human brain protein and high levels of circulating TNF alpha (TNFα), with the manifestation of CM in Gabonese children. METHODOLOGY: To study the role of self-reactive antibodies associated to the development of P. falciparum cerebral malaria, we used a combination of quantitative immunoblotting and multivariate analysis to analyse correlation between the reactivity of circulating IgG with a human brain protein extract and TNFα concentrations in cohorts of uninfected controls (UI) and P. falciparum-infected Gabonese children developing uncomplicated malaria (UM), severe non-cerebral malaria (SNCM), or CM. RESULTS/CONCLUSION: The repertoire of brain antigens recognized by plasma IgGs was more diverse in infected than in UI individuals. Anti-brain reactivity was significantly higher in the CM group than in the UM and SNCM groups. IgG self-reactivity to brain antigens was also correlated with plasma IgG levels and age. We found that 90% of CM patients displayed reactivity to a high-molecular mass band containing the spectrin non-erythroid alpha chain. Reactivity with this band was correlated with high TNFα concentrations in CM patients. These results strongly suggest that an antibody response to brain antigens induced by P. falciparum infection may be associated with pathogenic mechanisms in patients developing CM

Parent perceptions of the quality of life of pet dogs living with neuro-typically developing and neuro-atypically developing children: an exploratory study

There is growing scientific and societal recognition of the role that pet dogs can play in healthy development of children; both those who are neuro-typically developing and those who live with a neuro-developmental disorder, such as autism or attention deficit hyperactivity disorder. However, little attention has been paid to how living with children positively and negatively affects quality of life of a pet dog. In this exploratory study we conducted semi-structured interviews with parents of neuro-typically developing children (n = 18) and those with a neuro-developmental disorder (n = 18) who owned a pet dog, until no new factors were identified. Living with children brought potentially positive benefits to the dog’s life including: imposition of a routine, participation in recreational activities and the development of a strong bond between the child and the dog. The importance of maintaining a routine was particularly prevalent in families with children with neuro-developmental disorders. Potential negative factors included having to cope with child meltdowns and tantrums, over stimulation from child visitors, harsh contact and rough and tumble play with the child. The regularity and intensity of meltdowns and tantrums was particularly evident in responses from parents with children with a neuro-developmental disorder. However, child visitors and rough play and contact were mentioned similarly across the groups. Protective factors included having a safe haven for the dog to escape to, parent’s awareness of stress signs and child education in dog-interaction. Parents were also asked to complete a stress response scale to provide an initial quantitative comparison of stress responses between dogs living with the two family-types. Parents with neuro-typically developing children more frequently observed their dog rapidly running away from a situation and less frequently observed their dog widening their eyes, than parents with children with a neuro-developmental disorder. We propose the development of a stress audit based on the findings reported here, to prevent potential dangerous situations, which may lead to dog bites and dog relinquishment and allow owners to maximise the benefits of dog ownership

Mild Mitochondrial Uncoupling and Calorie Restriction Increase Fasting eNOS, Akt and Mitochondrial Biogenesis

Enhanced mitochondrial biogenesis promoted by eNOS activation is believed to play a central role in the beneficial effects of calorie restriction (CR). Since treatment of mice with dinitrophenol (DNP) promotes health and lifespan benefits similar to those observed in CR, we hypothesized that it could also impact biogenesis. We found that DNP and CR increase citrate synthase activity, PGC-1α, cytochrome c oxidase and mitofusin-2 expression, as well as fasting plasma levels of NO• products. In addition, eNOS and Akt phosphorylation in skeletal muscle and visceral adipose tissue was activated in fasting CR and DNP animals. Overall, our results indicate that systemic mild uncoupling activates eNOS and Akt-dependent pathways leading to mitochondrial biogenesis

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

CK2 Phosphorylation of Schistosoma mansoni HMGB1 Protein Regulates Its Cellular Traffic and Secretion but Not Its DNA Transactions

parasite resides in mesenteric veins where fecundated female worms lay hundred of eggs daily. Some of the egg antigens are trapped in the liver and induce a vigorous granulomatous response. High Mobility Group Box 1 (HMGB1), a nuclear factor, can also be secreted and act as a cytokine. Schistosome HMGB1 (SmHMGB1) is secreted by the eggs and stimulate the production of key cytokines involved in the pathology of schistosomiasis. Thus, understanding the mechanism of SmHMGB1 release becomes mandatory. Here, we addressed the question of how the nuclear SmHMGB1 can reach the extracellular space. eggs of infected animals and that SmHMGB1 that were localized in the periovular schistosomotic granuloma were phosphorylated.We showed that secretion of SmHMGB1 is regulated by phosphorylation. Moreover, our results suggest that egg-secreted SmHMGB1 may represent a new egg antigen. Therefore, the identification of drugs that specifically target phosphorylation of SmHMGB1 might block its secretion and interfere with the pathogenesis of schistosomiasis