Human rhinovirus-induced inflammatory responses are inhibited by phosphatidylserine containing liposomes

Human rhinovirus (HRV) infections are major contributors to the healthcare burden associated with acute exacerbations of chronic airway disease, such as chronic obstructive pulmonary disease and asthma. Cellular responses to HRV are mediated through pattern recognition receptors that may in part signal from membrane microdomains. We previously found Toll-like receptor signaling is reduced, by targeting membrane microdomains with a specific liposomal phosphatidylserine species, 1-stearoyl-2-arachidonoyl-sn-glycero-3-phospho-L-serine (SAPS). Here we explored the ability of this approach to target a clinically important pathogen. We determined the biochemical and biophysical properties and stability of SAPS liposomes and studied their ability to modulate rhinovirus-induced inflammation, measured by cytokine production, and rhinovirus replication in both immortalized and normal primary bronchial epithelial cells. SAPS liposomes rapidly partitioned throughout the plasma membrane and internal cellular membranes of epithelial cells. Uptake of liposomes did not cause cell death, but was associated with markedly reduced inflammatory responses to rhinovirus, at the expense of only modest non-significant increases in viral replication, and without impairment of interferon receptor signaling. Thus using liposomes of phosphatidylserine to target membrane microdomains is a feasible mechanism for modulating rhinovirus-induced signaling, and potentially a prototypic new therapy for viral-mediated inflammation.

Discriminating ambulation using a smart sensing plate

The automated sensing scheme described in this paper has the potential to automatically capture, discriminate and classify transients in gait. The mechanical simplicity of the walking platform offers advantages over standard force plates. There is less restriction on dimensions offering the opportunity for multi-contact and multiple steps. This addresses the challenge of patient targeting and the evaluation of patients in a variety of ambulatory applications. In this work the sensitivity of the distributive tactile sensing method has been investigated experimentally. Using coupled time series data from a small number of sensors, gait patterns are compared with stored templates using a pattern recognition algorithm. By using a neural network these patterns were interpreted classifying normal and affected walking events with an accuracy of just under 90%. This system has potential in gait analysis and rehabilitation as a tool for early diagnosis in walking disorders, for determining response to therapy and for identifying changes between pre and post operative gait. Copyright © 2009 by ASME.

Source localization of reaction-diffusion models for brain tumors

We propose a mathematically well-founded approach for locating the source (initial state) of density functions evolved within a nonlinear reaction-diffusion model. The reconstruction of the initial source is an ill-posed inverse problem since the solution is highly unstable with respect to measurement noise. To address this instability problem, we introduce a regularization procedure based on the nonlinear Landweber method for the stable determination of the source location. This amounts to solving a sequence of well-posed forward reaction-diffusion problems. The developed framework is general, and as a special instance we consider the problem of source localization of brain tumors. We show numerically that the source of the initial densities of tumor cells are reconstructed well on both imaging data consisting of simple and complex geometric structures.

Edge centrality via the Holevo quantity

In the study of complex networks, vertex centrality measures are used to identify the most important vertices within a graph. A related problem is that of measuring the centrality of an edge. In this paper, we propose a novel edge centrality index rooted in quantum information. More specifically, we measure the importance of an edge in terms of the contribution that it gives to the Von Neumann entropy of the graph. We show that this can be computed in terms of the Holevo quantity, a well known quantum information theoretical measure. While computing the Von Neumann entropy and hence the Holevo quantity requires computing the spectrum of the graph Laplacian, we show how to obtain a simplified measure through a quadratic approximation of the Shannon entropy. This in turns shows that the proposed centrality measure is strongly correlated with the negative degree centrality on the line graph. We evaluate our centrality measure through an extensive set of experiments on real-world as well as synthetic networks, and we compare it against commonly used alternative measures.

The average mixing matrix signature

Laplacian-based descriptors, such as the Heat Kernel Signature and the Wave Kernel Signature, allow one to embed the vertices of a graph onto a vectorial space, and have been successfully used to find the optimal matching between a pair of input graphs. While the HKS uses a heat di↵usion process to probe the local structure of a graph, the WKS attempts to do the same through wave propagation. In this paper, we propose an alternative structural descriptor that is based on continuoustime quantum walks. More specifically, we characterise the structure of a graph using its average mixing matrix. The average mixing matrix is a doubly-stochastic matrix that encodes the time-averaged behaviour of a continuous-time quantum walk on the graph. We propose to use the rows of the average mixing matrix for increasing stopping times to develop a novel signature, the Average Mixing Matrix Signature (AMMS). We perform an extensive range of experiments and we show that the proposed signature is robust under structural perturbations of the original graphs and it outperforms both the HKS and WKS when used as a node descriptor in a graph matching task.

Quantum kernels for unattributed graphs using discrete-time quantum walks

In this paper, we develop a new family of graph kernels where the graph structure is probed by means of a discrete-time quantum walk. Given a pair of graphs, we let a quantum walk evolve on each graph and compute a density matrix with each walk. With the density matrices for the pair of graphs to hand, the kernel between the graphs is defined as the negative exponential of the quantum Jensen–Shannon divergence between their density matrices. In order to cope with large graph structures, we propose to construct a sparser version of the original graphs using the simplification method introduced in Qiu and Hancock (2007). To this end, we compute the minimum spanning tree over the commute time matrix of a graph. This spanning tree representation minimizes the number of edges of the original graph while preserving most of its structural information. The kernel between two graphs is then computed on their respective minimum spanning trees. We evaluate the performance of the proposed kernels on several standard graph datasets and we demonstrate their effectiveness and efficiency.

Towards person-centered neuroimaging markers for resilience and vulnerability in Bipolar Disorder

Improved clinical care for Bipolar Disorder (BD) relies on the identification of diagnostic markers that can reliably detect disease-related signals in clinically heterogeneous populations. At the very least, diagnostic markers should be able to differentiate patients with BD from healthy individuals and from individuals at familial risk for BD who either remain well or develop other psychopathology, most commonly Major Depressive Disorder (MDD). These issues are particularly pertinent to the development of translational applications of neuroimaging as they represent challenges for which clinical observation alone is insufficient. We therefore applied pattern classification to task-based functional magnetic resonance imaging (fMRI) data of the n-back working memory task, to test their predictive value in differentiating patients with BD (n=30) from healthy individuals (n=30) and from patients' relatives who were either diagnosed with MDD (n=30) or were free of any personal lifetime history of psychopathology (n=30). Diagnostic stability in these groups was confirmed with 4-year prospective follow-up. Task-based activation patterns from the fMRI data were analyzed with Gaussian Process Classifiers (GPC), a machine learning approach to detecting multivariate patterns in neuroimaging datasets. Consistent significant classification results were only obtained using data from the 3-back versus 0-back contrast. Using contrast, patients with BD were correctly classified compared to unrelated healthy individuals with an accuracy of 83.5%, sensitivity of 84.6% and specificity of 92.3%. Classification accuracy, sensitivity and specificity when comparing patients with BD to their relatives with MDD, were respectively 73.1%, 53.9% and 94.5%. Classification accuracy, sensitivity and specificity when comparing patients with BD to their healthy relatives were respectively 81.8%, 72.7% and 90.9%. We show that significant individual classification can be achieved using whole brain pattern analysis of task-based working memory fMRI data. The high accuracy and specificity achieved by all three classifiers suggest that multivariate pattern recognition analyses can aid clinicians in the clinical care of BD in situations of true clinical uncertainty regarding the diagnosis and prognosis.