Stains Induce Apoptosis and Autophagy in Primary and Transformed Mast Cells

Statin drugs are widely employed in the clinic to reduce serum low density lipoproteins (LDLs) in patients with hypocholesteremia. In addition to their cholesterol-lowering effects through HMG CoA reductase antagonism, isoprenyl lipids necessary for membrane anchorage and signaling of small G-proteins are abrogated. We previously found that statins suppress mast cell activation in murine and human cells, suggesting these drugs might be useful in treating allergic disease. While mast cell function is critical to allergic inflammation, mast cell hyperplasia and survival also impact these diseases, and were not studied in our previous work. In this study, we describe Fluvastatin-mediated apoptosis in both primary and transformed mast cells. An IC50 was achieved between 1-5μM in both systems, and apoptosis was preceded by mitochondrial dysfunction and caspase release. In addition to apoptosis, our work also uncovered evidence of autophagy, which can serve as a compensatory mechanism during apoptosis. Interestingly, autophagy appeared to be cyto-protective in the primary cells yet cytotoxic in transformed mast cells. These findings offer insight into the mechanisms of mast cell survival and support the possible utility of statins in mast cell-associated allergic and neoplastic diseases

Hierarchical Stochastic Block Model for Community Detection in Multiplex Networks

Multiplex networks have become increasingly more prevalent in many fields, and have emerged as a powerful tool for modeling the complexity of real networks. There is a critical need for developing inference models for multiplex networks that can take into account potential dependencies across different layers, particularly when the aim is community detection. We add to a limited literature by proposing a novel and efficient Bayesian model for community detection in multiplex networks. A key feature of our approach is the ability to model varying communities at different network layers. In contrast, many existing models assume the same communities for all layers. Moreover, our model automatically picks up the necessary number of communities at each layer (as validated by real data examples). This is appealing, since deciding the number of communities is a challenging aspect of community detection, and especially so in the multiplex setting, if one allows the communities to change across layers. Borrowing ideas from hierarchical Bayesian modeling, we use a hierarchical Dirichlet prior to model community labels across layers, allowing dependency in their structure. Given the community labels, a stochastic block model (SBM) is assumed for each layer. We develop an efficient slice sampler for sampling the posterior distribution of the community labels as well as the link probabilities between communities. In doing so, we address some unique challenges posed by coupling the complex likelihood of SBM with the hierarchical nature of the prior on the labels. An extensive empirical validation is performed on simulated and real data, demonstrating the superior performance of the model over single-layer alternatives, as well as the ability to uncover interesting structures in real networks

Electrochemical Characterization of Nonaqueous Systems for Secondary Battery Application Quarterly Report, May - Jul. 1968

Electrochemical characterization of nonaqueous systems for secondary battery applicatio

Electrochemical characterization of nonaqueous systems for secondary battery application Quarterly report, Aug. - Oct. 1967

Multisweep cyclic voltammograms for electrochemical characterization of nonaqueous systems for secondary battery application

Electrochemical characterization of nonaqueous systems for secondary battery application

Electrochemical evaluation of electrode organic electrolyte combinations for rechargeable battery system

Electrochemical characterization of nonaqueous systems for secondary battery application Quarterly report, Nov. 1967 - Jan. 1968

Multisweep cyclic voltammograms for electrochemical characterization of nonaqueous systems for secondary battery application

Comparison of Thematic Maps Using Symbolic Entropy

Comparison of thematic maps is an important task in a number of disciplines. Map comparison has traditionally been conducted using cell-by-cell agreement indicators, such as the Kappa measure. More recently, other methods have been proposed that take into account not only spatially coincident cells in two maps, but also their surroundings or the spatial structure of their differences. The objective of this paper is to propose a framework for map comparison that considers 1) the patterns of spatial association in two maps, in other words, the map elements in their surroundings; 2) the equivalence of those patterns; and 3) the independence of patterns between maps. Two new statistics for the spatial analysis of qualitative data are introduced. These statistics are based on the symbolic entropy of the maps, and function as measures of map compositional equivalence and independence. As well, all inferential elements to conduct hypothesis testing are developed. The framework is illustrated using real and synthetic maps. Key word: Thematic maps, map comparison, qualitative variables, spatial association, symbolic entropy, hypothesis tests

A Novel Immunostimulatory Platform for Amplifying the Abscopal Response Rates of Radiation Therapy

Radiation therapy (RT) is one of the primary treatment modalities for head and neck squamous cell carcinoma (HNSCC). At the time of diagnosis two-thirds of HNSCC patients have local-advanced disease and 50-60% of these patients will experience a local-regional or metastatic relapse within three years. Improving the immunogenic response of RT may help address this clinical problem. However, current RT regimens have failed to reliably generate robust antitumor immunity as evidenced by the rarity of clinical abscopal responses. Recently we engineered a chimeric fusion molecule called Flagrp170, a novel immunostimulatory agent highly capable of promoting antigen presentation and T-cell activation. We hypothesize that the combination of RT and Flagrp170 provides superior immunogenic signals producing effective and durable antitumor immunity against HNSCC. We report that administration of Flagrp170 to the tumor sites upon RT using a small animal radiation research platform (SARPP) results in potent activation of antigen-presenting cells, increased functionality of tumor-infiltrating T-cells, and systemic immune augmentation. Additionally, the combination treatment is able to reduce the dose of RT required for tumor control and protects previously cured animals from subsequent tumor re-challenge. Finally, the combination treatment can successfully control the contralateral untreated tumors, supporting the superior activity of Flagrp170 in potentiating abscopal responses of RT. Our data suggest that the Flagrp170 may be used to enhance immunogenic cancer cell death in RT and resultant protective antitumor immunity can potentially help reduce post-RT recurrence of HNSCC