Connectivity Mapping (ssCMap) To Predict A20 Inducing Drugs: Anti-inflammatory Action In Cystic Fibrosis

Cystic Fibrosis (CF) lung disease is characterised by a chronic and exaggerated inflammation in the airways. Despite recent developments to therapeutically overcome the underlying functional defect in CFTR (cystic fibrosis transmembrane conductance regulator), there is still an unmet need to also normalise the inflammatory response. The prolonged and heightened inflammatory response in CF is in part mediated by a lack of intrinsic downregulation of the pro-inflammatory NF-kB pathway. We have previously identified reduced expression of the NF-kB down-regulator A20 in CF as a key target to normalise the inflammatory response. Here we have used publically available gene array expression data together with sscMap (statistically significant connections’map)to successfully predict drugs already licensed for the use in humans to induce A20 mRNA and protein expression and thereby reduce inflammation. The effect of the predicted drugs on A20 and NFkB (p65) expression (mRNA) as well as pro-inflammatory cytokine release (IL-8) in the presence and absence of bacterial LPS was shown in bronchial epithelial cells lines (16HBE14o-, CFBE41o-) and in primary nasal epithelial cells (PNECs) from patients with CF (Phe508del homozygous) and non-CF controls. Additionally, the specificity of the drug action on A20 was confirmed using cell lines with TNFAIP3 (A20) knockdown (siRNA). We also show that the A20 inducing effect of ikarugamycin and quercetin is lower in CF derived airway epithelial cells than in non-CF cells.

Spectrally isometric elementary operators

We present criteria for unital elementary operators (of small length) on unital semisimple Banach algebras to be spectral isometries. The surjective ones among them turn out to be algebra automorphisms.

More elementary operators that are spectrally bounded

We discuss some necessary and some sufficient conditions for an elementary operator x↦∑ⁿ_i=1a_ixb_i on a Banach algebra A to be spectrally bounded. In the case of length three, we obtain a complete characterisation when A acts irreducibly on a Banach space of dimension greater than three.

Locally quasi-nilpotent elementary operators

Let A be a unital dense algebra of linear mappings on a complex vector space X. Let φ = Σⁿ _i=1 M_ai,_bi be a locally quasi-nilpotent elementary operator of length n on A. We show that, if {a1, . . . , an} is locally linearly independent, then the local dimension of V (φ) = span{b_ia_j : 1 ≤ i, j ≤ n} is at most n(n−1) 2 . If ldim V (φ) = n(n−1) 2 , then there exists a representation of φ as φ = Σⁿ _i=1 M_ui,_vi with v_iu_j = 0 for i ≥ j. Moreover, we give a complete characterization of locally quasinilpotent elementary operators of length 3.

Transcallosal connectivity of the human cortical motor network

The organizational and architectural configuration of white matter pathways connecting brain regions has ramifications for all facets of the human condition, including manifestations of incipient neurodegeneration. Although diffusion tensor imaging (DTI) has been used extensively to visualize white matter connectivity, due to the widespread presence of crossing fibres, the lateral projections of the corpus callosum are not normally detected using this methodology. Detailed knowledge of the transcallosal connectivity of the human cortical motor network has therefore remained elusive. We employed constrained spherical deconvolution (CSD) tractography - an approach that is much less susceptible to the influence of crossing fibres, in order to derive complete in-vivo characterizations of white matter pathways connecting specific motor cortical regions to their counterparts and other loci in the opposite hemisphere. The revealed patterns of connectivity closely resemble those derived from anatomical tracing in primates. It was established that dorsal premotor cortex (PMd) and supplementary motor area (SMA) have extensive interhemispheric connectivity - exhibiting both dense homologous projections, and widespread structural relations with every other region in the contralateral motor network. Through this in-vivo portrayal, the importance of non-primary motor regions for interhemispheric communication is emphasized. Additionally, distinct connectivity profiles were detected for the anterior and posterior subdivisions of primary motor cortex. The present findings provide a comprehensive representation of transcallosal white matter projections in humans, and have the potential to inform the development of models and hypotheses relating structural and functional brain connectivity.

Elementary operators-still not elementary?

Properties of elementary operators, that is, finite sums of two-sided multiplications on a Banach algebra, have been studied under a vast variety of aspects by numerous authors. In this paper we review recent advances in a new direction that seems not to have been explored before: the question when an elementary operator is spectrally bounded or spectrally isometric. As with other investigations, a number of subtleties occur which show that elementary operators are still not elementary to handle.

Network Connectivity under Node Failure

We examine a non-cooperative model of network formation where players may stop functioning with a given probability. When this happens all the links associated with this player are no longer available in the network. In the model, players receive benefits from connecting directly and indirectly to other agents in the network through costly links. We identify conditions under which a Nash network will remain connected after the loss of k nodes by introducing the notion of k-Node Super Connectivity network. We identify similar conditions for efficient networks as well.

Non-Gaussian distribution of collective operators in quantum spin chains

We numerically analyse the behavior of the full distribution of collective observables in quantum spin chains. While most of previous studies of quantum critical phenomena are limited to the first moments, here we demonstrate how quantum fluctuations at criticality lead to highly non-Gaussian distributions. Interestingly, we show that the distributions for different system sizes collapse on thesame curve after scaling for a wide range of transitions: first and second order quantum transitions and transitions of the Berezinskii–Kosterlitz–Thouless type. We propose and analyse the feasibility of an experimental reconstruction of the distribution using light–matter interfaces for atoms in optical lattices or in optical resonators.

Orbits of semigroups of truncated convolution operators

We prove that a semigroup generated by finitely many truncated convolution operators on $L_p[0, 1]$ with 1 ≤ p < ∞ is non-supercyclic. On the other hand, there is a truncated convolution operator, which possesses irregular vectors.

Existence of disjoint weakly mixing operators that fail to satisfy the Disjoint Hypercyclicity Criterion

Recently, Bès, Martin, and Sanders [11] provided examples of disjoint hypercyclic operators which fail to satisfy the Disjoint Hypercyclicity Criterion. However, their operators also fail to be disjoint weakly mixing. We show that every separable, infinite dimensional Banach space admits operators T1,T2,…,TN with N⩾2 which are disjoint weakly mixing, and still fail to satisfy the Disjoint Hypercyclicity Criterion, answering a question posed in [11]. Moreover, we provide examples of disjoint hypercyclic operators T1, T2 whose corresponding set of disjoint hypercyclic vectors is nowhere dense, answering another question posed in [11]. In fact, we explicitly describe their set of disjoint hypercyclic vectors. Those same disjoint hypercyclic operators fail to be disjoint topologically transitive. Lastly, we create examples of two families of d-hypercyclic operators which fail to have any d-hypercyclic vectors in common.