Lagrangian Framework for Systems Composed of High-Loss and Lossless Components

Using a Lagrangian mechanics approach, we construct a framework to study the dissipative properties of systems composed of two components one of which is highly lossy and the other is lossless. We have shown in our previous work that for such a composite system the modes split into two distinct classes, high-loss and low-loss, according to their dissipative behavior. A principal result of this paper is that for any such dissipative Lagrangian system, with losses accounted by a Rayleigh dissipative function, a rather universal phenomenon occurs, namely, selective overdamping: The high-loss modes are all overdamped, i.e., non-oscillatory, as are an equal number of low-loss modes, but the rest of the low-loss modes remain oscillatory each with an extremely high quality factor that actually increases as the loss of the lossy component increases. We prove this result using a new time dynamical characterization of overdamping in terms of a virial theorem for dissipative systems and the breaking of an equipartition of energy.Comment: 53 pages, 1 figure; Revision of our original manuscript to incorporate suggestions from refere

Quartic double solids with ordinary singularities

We study the mixed Hodge structure on the third homology group of a threefold which is the double cover of projective three-space ramified over a quartic surface with a double conic. We deal with the Torelli problem for such threefolds.Comment: 14 pages, presented at the Conference Arnol'd 7

Toward harmonized phenotyping of human myeloid-derived suppressor cells by flow cytometry: results from an interim study

There is an increasing interest for monitoring circulating myeloid-derived suppressor cells (MDSCs) in cancer patients, but there are also divergences in their phenotypic definition. To overcome this obstacle, the Cancer Immunoguiding Program under the umbrella of the Association of Cancer Immunotherapy is coordinating a proficiency panel program that aims at harmonizing MDSC phenotyping. After a consultation period, a two-stage approach was designed to harmonize MDSC phenotype. In the first step, an international consortium of 23 laboratories immunophenotyped 10 putative MDSC subsets on pretested, peripheral blood mononuclear cells of healthy donors to assess the level of concordance and define robust marker combinations for the identification of circulating MDSCs. At this stage, no mandatory requirements to standardize reagents or protocols were introduced. Data analysis revealed a small intra-laboratory, but very high inter-laboratory variance for all MDSC subsets, especially for the granulocytic subsets. In particular, the use of a dead-cell marker altered significantly the reported percentage of granulocytic MDSCs, confirming that these cells are especially sensitive to cryopreservation and/or thawing. Importantly, the gating strategy was heterogeneous and associated with high inter-center variance. Overall, our results document the high variability in MDSC phenotyping in the multicenter setting if no harmonization/standardization measures are applied. Although the observed variability depended on a number of identified parameters, the main parameter associated with variation was the gating strategy. Based on these findings, we propose further efforts to harmonize marker combinations and gating parameters to identify strategies for a robust enumeration of MDSC subsets

Dissipative Properties of Systems Composed of High-Loss and Lossless Components

We study here dissipative properties of systems composed of two components one of which is highly lossy and the other is lossless. A principal result of our studies is that all the eigenmodes of such a system split into two distinct classes characterized as high-loss and low-loss. Interestingly, this splitting is more pronounced the higher the loss of the lossy component. In addition, the real frequencies of the high-loss eigenmodes can become very small and even can vanish entirely, which is the case of overdamping.Comment: Revision; Improved exposition and typos corrected; 45 pages, 4 figure

Two-dimensional model of dynamical fermion mass generation in strongly coupled gauge theories

We generalize the $N_F=2$ Schwinger model on the lattice by adding a charged scalar field. In this so-called $\chi U\phi_2$ model the scalar field shields the fermion charge, and a neutral fermion, acquiring mass dynamically, is present in the spectrum. We study numerically the mass of this fermion at various large fixed values of the gauge coupling by varying the effective four-fermion coupling, and find an indication that its scaling behavior is the same as that of the fermion mass in the chiral Gross-Neveu model. This suggests that the $\chi U\phi_2$ model is in the same universality class as the Gross-Neveu model, and thus renormalizable and asymptotic free at arbitrary strong gauge coupling.Comment: 18 pages, LaTeX2e, requires packages rotating.sty and curves.sty from CTA

Interferon-gamma and IL-5 associated cell-mediated immune responses to HPV16 E2 and E6 distinguish between persistent oral HPV16 infections and noninfected mucosa

Objectives: Natural history of human papillomavirus (HPV) infection in the head and neck region is poorly understood, and their impact on collective HPV-specific immunity is not known. Materials and methods: In this study, we have performed a systematic analysis of HPV16-specific cell-mediated immunity (CMI) in 21 women with known oral and genital HPV DNA status and HPV serology (Ab) based on 6-year follow-up data. These women being a subgroup from the Finnish Family HPV Study were recalled for blood sampling to be tested for their CMI-responses to HPV16 E2, E6, and E7 peptides. Results: The results showed that HPV16 E2-specific lymphocyte proliferation was more prevalent in women who tested HPV16 DNA negative in oral mucosa and were either HPV16 seropositive or negative than in HPV16 DNA+/Ab+ women (p = 0.046 and p = 0.035). In addition, the HPV16 DNA-/Ab- women most often displayed E6-specific proliferation (p = 0.020). Proportional cytokine profiles indicated that oral HPV16-negative women were characterized by prominent IFN-gamma and IL-5 secretion not found in women with persisting oral HPV16 (p = 0.014 and p = 0.040, respectively). Conclusions: Our results indicate that the naturally arising immune response induced by oral HPV infections displays a mixed Th1/Th2/Th17 cytokine profile while women with persisting oral HPV16 might have an impaired HPV16-specific CMI, shifted partly toward a Th2 profile, similarly as seen earlier among patients with high-grade genital HPV lesions. Thus, the lack of HPV 16 E2 and E6 specific T memory cells and Th2 cytokines might also predispose women for persistent oral HPV16 infection which might be related to the risk of cancer.Peer reviewe

Sustainability in Turbulent Times: Lessons from the Nexus Network for supporting transdisciplinary research

This is the final version. Available from the Nexus Network via the link in this recordEconomic and Social Research Council (ESRC

Differential effects of saturated and unsaturated fatty acids on autophagy in pancreatic β-cells

Long-chain saturated fatty acids are lipotoxic to pancreatic β-cells, whereas most unsaturates are better tolerated and some may even be cytoprotective. Fatty acids alter autophagy in β-cells and there is increasing evidence that such alterations can impact directly on the regulation of viability. Accordingly, we have compared the effects of palmitate (C16:0) and palmitoleate (C16:1) on autophagy in cultured β-cells and human islets. Treatment of BRIN-BD11 β-cells with palmitate led to enhanced autophagic activity, as judged by cleavage of microtubule-associated protein 1 light chain 3-I (LC3-I) and this correlated with a marked loss of cell viability in the cells. In addition, transfection of these cells with an mCherry-YFP-LC3 reporter construct revealed the accumulation of autophagosomes in palmitate-treated cells, indicating an impairment of autophagosome-lysosome fusion. This was also seen upon addition of the vacuolar ATPase inhibitor, bafilomycin A1. Exposure of BRIN-BD11 cells to palmitoleate (C16:1) did not lead directly to changes in autophagic activity or flux, but it antagonised the actions of palmitate. In parallel, palmitoleate also improved the viability of palmitate-treated BRIN-BD11 cells. Equivalent responses were observed in INS-1E cells and in isolated human islets. Taken together, these data suggest that palmitate may cause an impairment of autophagosome-lysosome fusion. These effects were not reproduced by palmitoleate which, instead, antagonised the responses mediated by palmitate suggesting that attenuation of β-cell stress may contribute to the improvement in cell viability caused by the mono-unsaturated fatty acid.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.The authors are grateful to Diabetes UK for financial support via project grants 14/0005093 and 15/0005156 (to N G M) and a PhD studentship (14/0005093) to Patricia Thomas. They also thank Dr Jon Lane (University of Bristol) for the kind gift of a dual-fluorescence LC3 reporter construct.accepted version (12 month embargo), submitted versio