Calibrated cycles and T-duality

For Hitchin's generalised geometries we introduce and analyse the concept of a structured submanifold which encapsulates the classical notion of a calibrated submanifold. Under a suitable integrability condition on the ambient geometry, these generalised calibrated cycles minimise a functional occurring as D-brane energy in type II string theories, involving both so-called NS-NS- and R-R-fields. Further, we investigate the behaviour of calibrated cycles under T-duality and construct non-trivial examples.Comment: 43 pages. v4: formalism and T-duality part considerably expande

High energy limits of Laplace-type and Dirac-type eigenfunctions and frame flows

We relate high-energy limits of Laplace-type and Dirac-type operators to frame flows on the corresponding manifolds, and show that the ergodicity of frame flows implies quantum ergodicity in an appropriate sense for those operators. Observables for the corresponding quantum systems are matrix-valued pseudodifferential operators and therefore the system remains non-commutative in the high-energy limit. We discuss to what extent the space of stationary high-energy states behaves classically.Comment: 26 pages, latex2

Copy number variant discrepancy resolution using the ClinGen dosage sensitivity map results in updated clinical interpretations in ClinVar

Conflict resolution in genomic variant interpretation is a critical step toward improving patient care. Evaluating interpretation discrepancies in copy number variants (CNVs) typically involves assessing overlapping genomic content with focus on genes/regions that may be subject to dosage sensitivity (haploinsufficiency (HI) and/or triplosensitivity (TS)). CNVs containing dosage sensitive genes/regions are generally interpreted as â likely pathogenicâ (LP) or â pathogenicâ (P), and CNVs involving the same known dosage sensitive gene(s) should receive the same clinical interpretation. We compared the Clinical Genome Resource (ClinGen) Dosage Map, a publicly available resource documenting known HI and TS genes/regions, against germline, clinical CNV interpretations within the ClinVar database. We identified 251 CNVs overlapping known dosage sensitive genes/regions but not classified as LP or P; these were sent back to their original submitting laboratories for reâ evaluation. Of 246 CNVs reâ evaluated, an updated clinical classification was warranted in 157 cases (63.8%); no change was made to the current classification in 79 cases (32.1%); and 10 cases (4.1%) resulted in other types of updates to ClinVar records. This effort will add curated interpretation data into the public domain and allow laboratories to focus attention on more complex discrepancies.The ClinGen Dosage Sensitivity (DS) Map provides evidenceâ based assessments of the haploinsufficiency and triplosensitivity of genes/genomic regions. We identified 251 clinical copy number variants (CNVs) in ClinVar that overlapped known DS genes/regions but were not interpreted as â likely pathogenicâ or â pathogenic;â these were sent back to their original laboratories for reâ evaluation. Of the 246 that were reâ evaluated, 63.0% resulted in updated classifications, showing that the ClinGen DS Map can be an effective initial step in CNV classification discrepancy resolution.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146425/1/humu23610_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146425/2/humu23610.pd

Human neutrophil clearance of bacterial pathogens triggers anti-microbial gamma delta T cell responses in early infection

Human blood Vc9/Vd2 T cells, monocytes and neutrophils share a responsiveness toward inflammatory chemokines and are rapidly recruited to sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients may therefore provide crucial insight into inflammatory events. Our present data demonstrate that Vc9/Vd2 T cells provide potent survival signals resulting in neutrophil activation and the release of the neutrophil chemoattractant CXCL8 (IL-8). In turn, Vc9/Vd2 T cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of CD69, interferon (IFN)-c and tumor necrosis factor (TNF)-a. This response is dependent on the ability of these bacteria to produce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact of Vc9/Vd2 T cells with accessory monocytes through lymphocyte function-associated antigen-1 (LFA-1), and results in a TNF-a dependent proliferation of Vc9/Vd2 T cells. The antibiotic fosmidomycin, which targets the HMB-PP biosynthesis pathway, not only has a direct antibacterial effect on most HMB-PP producing bacteria but also possesses rapid anti-inflammatory properties by inhibiting cd T cell responses in vitro. Patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis – characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity – show a selective activation of local Vc9/Vd2 T cells by HMB-PP producing but not by HMB-PP deficient bacterial pathogens. The cd T celldriven perpetuation of inflammatory responses during acute peritonitis is associated with elevated peritoneal levels of cd T cells and TNF-a and detrimental clinical outcomes in infections caused by HMB-PP positive microorganisms. Taken together, our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive cd T cells in early infection and suggest novel diagnostic and therapeutic approaches.Martin S. Davey, Chan-Yu Lin, Gareth W. Roberts, Sinéad Heuston, Amanda C. Brown, James A. Chess, Mark A. Toleman, Cormac G.M. Gahan, Colin Hill, Tanya Parish, John D. Williams, Simon J. Davies, David W. Johnson, Nicholas Topley, Bernhard Moser and Matthias Eber

Integrative Network Biology: Graph Prototyping for Co-Expression Cancer Networks

Network-based analysis has been proven useful in biologically-oriented areas, e.g., to explore the dynamics and complexity of biological networks. Investigating a set of networks allows deriving general knowledge about the underlying topological and functional properties. The integrative analysis of networks typically combines networks from different studies that investigate the same or similar research questions. In order to perform an integrative analysis it is often necessary to compare the properties of matching edges across the data set. This identification of common edges is often burdensome and computational intensive. Here, we present an approach that is different from inferring a new network based on common features. Instead, we select one network as a graph prototype, which then represents a set of comparable network objects, as it has the least average distance to all other networks in the same set. We demonstrate the usefulness of the graph prototyping approach on a set of prostate cancer networks and a set of corresponding benign networks. We further show that the distances within the cancer group and the benign group are statistically different depending on the utilized distance measure

Wave decay on convex co-compact hyperbolic manifolds

For convex co-compact hyperbolic quotients X=\Gamma\backslash\hh^{n+1}, we analyze the long-time asymptotic of the solution of the wave equation $u(t)$ with smooth compactly supported initial data $f=(f_0,f_1)$. We show that, if the Hausdorff dimension $\delta$ of the limit set is less than $n/2$, then u(t) = C_\delta(f) e^{(\delta-\ndemi)t} / \Gamma(\delta-n/2+1) + e^{(\delta-\ndemi)t} R(t) where $C_{\delta}(f)\in C^\infty(X)$ and ||R(t)||=\mc{O}(t^{-\infty}). We explain, in terms of conformal theory of the conformal infinity of $X$, the special cases \delta\in n/2-\nn where the leading asymptotic term vanishes. In a second part, we show for all \eps>0 the existence of an infinite number of resonances (and thus zeros of Selberg zeta function) in the strip \{-n\delta-\eps<\Re(\la)<\delta\}. As a byproduct we obtain a lower bound on the remainder $R(t)$ for generic initial data $f$.Comment: 18 page

Characterizing global evolutions of complex systems via intermediate network representations

Recent developments in measurement techniques have enabled us to observe the time series of many components simultaneously. Thus, it is important to understand not only the dynamics of individual time series but also their interactions. Although there are many methods for analysing the interaction between two or more time series, there are very few methods that describe global changes of the interactions over time. Here, we propose an approach to visualise time evolution for the global changes of the interactions in complex systems. This approach consists of two steps. In the first step, we construct a meta-time series of networks. In the second step, we analyse and visualise this meta-time series by using distance and recurrence plots. Our two-step approach involving intermediate network representations elucidates the half-a-day periodicity of foreign exchange markets and a singular functional network in the brain related to perceptual alternations

Prototype generation on structural data using dissimilarity space representation

Data reduction techniques play a key role in instance-based classification to lower the amount of data to be processed. Among the different existing approaches, prototype selection (PS) and prototype generation (PG) are the most representative ones. These two families differ in the way the reduced set is obtained from the initial one: While the former aims at selecting the most representative elements from the set, the latter creates new data out of it. Although PG is considered to delimit more efficiently decision boundaries, the operations required are not so well defined in scenarios involving structural data such as strings, trees, or graphs. This work studies the possibility of using dissimilarity space (DS) methods as an intermediate process for mapping the initial structural representation to a statistical one, thereby allowing the use of PG methods. A comparative experiment over string data is carried out in which our proposal is faced to PS methods on the original space. Results show that the proposed strategy is able to achieve significantly similar results to PS in the initial space, thus standing as a clear alternative to the classic approach, with some additional advantages derived from the DS representation.This work was partially supported by the Spanish Ministerio de Educación, Cultura y Deporte through a FPU fellowship (AP2012–0939), Vicerrectorado de Investigación, Desarrollo e Innovación de la Universidad de Alicante through FPU program (UAFPU2014–5883), and the Spanish Ministerio de Economía y Competitividad through Project TIMuL (No. TIN2013-48152-C2-1-R supported by EU FEDER funds)