Temperature dependent study of the spin dynamics of coupled Y3_3Fe5_5O12_{12}/Gd3_3Fe5_5O12_{12}/Pt trilayers

In this study, we investigate the dynamic response of a Y$_3$Fe$_5$O$_{12}$ (YIG)/ Gd$_3$Fe$_5$O$_{12}$ (GdIG)/ Pt trilayer system by measurements of the ferromagnetic resonance (FMR) and the pumped spin current detected by the inverse spin Hall effect. This trilayer system offers the unique opportunity to investigate the spin dynamics of the ferrimagnetic GdIG, close to its compensation temperature. We show that our trilayer acts as a highly tunable spin current source. Our experimental results are supported by micro-magnetic simulations. As the detected spin current in the top Pt layer is distinctly dominated by the GdIG layer, this gives the unique opportunity to investigate the excitation and dynamic properties of GdIG while comparing it to the broadband FMR absorption spectrum of the heterostructure

Polarization of Human Macrophages by Interleukin-4 Does Not Require ATP-Citrate Lyase

Macrophages exposed to the Th2 cytokines interleukin (IL) IL-4 and IL-13 exhibit a distinct transcriptional response, commonly referred to as M2 polarization. Recently, IL-4-induced polarization of murine bone marrow-derived macrophages (BMDMs) has been linked to acetyl-CoA levels through the activity of the cytosolic acetyl-CoA-generating enzyme ATP-citrate lyase (ACLY). Here, we studied how ACLY regulated IL-4-stimulated gene expression in human monocyte-derived macrophages (MDMs). Although multiple ACLY inhibitors attenuated IL-4-induced target gene expression, this effect could not be recapitulated by silencing ACLY expression. Furthermore, ACLY inhibition failed to alter cellular acetyl-CoA levels and histone acetylation. We generated ACLY knockout human THP-1 macrophages using CRISPR/Cas9 technology. While these cells exhibited reduced histone acetylation levels, IL-4-induced gene expression remained intact. Strikingly, ACLY inhibitors still suppressed induction of target genes by IL-4 in ACLY knockout cells, suggesting off-target effects of these drugs. Our findings suggest that ACLY may not be the major regulator of nucleocytoplasmic acetyl-CoA and IL-4-induced polarization in human macrophages. Furthermore, caution should be warranted in interpreting the impact of pharmacological inhibition of ACLY on gene expression

Multiple Events Lead to Dendritic Spine Loss in Triple Transgenic Alzheimer's Disease Mice

The pathology of Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β (Aβ) peptide, hyperphosphorylated tau protein, neuronal death, and synaptic loss. By means of long-term two-photon in vivo imaging and confocal imaging, we characterized the spatio-temporal pattern of dendritic spine loss for the first time in 3xTg-AD mice. These mice exhibit an early loss of layer III neurons at 4 months of age, at a time when only soluble Aβ is abundant. Later on, dendritic spines are lost around amyloid plaques once they appear at 13 months of age. At the same age, we observed spine loss also in areas apart from amyloid plaques. This plaque independent spine loss manifests exclusively at dystrophic dendrites that accumulate both soluble Aβ and hyperphosphorylated tau intracellularly. Collectively, our data shows that three spatio-temporally independent events contribute to a net loss of dendritic spines. These events coincided either with the occurrence of intracellular soluble or extracellular fibrillar Aβ alone, or the combination of intracellular soluble Aβ and hyperphosphorylated tau

PEtab -- interoperable specification of parameter estimation problems in systems biology

Reproducibility and reusability of the results of data-based modeling studies are essential. Yet, there has been -- so far -- no broadly supported format for the specification of parameter estimation problems in systems biology. Here, we introduce PEtab, a format which facilitates the specification of parameter estimation problems using Systems Biology Markup Language (SBML) models and a set of tab-separated value files describing the observation model and experimental data as well as parameters to be estimated. We already implemented PEtab support into eight well-established model simulation and parameter estimation toolboxes with hundreds of users in total. We provide a Python library for validation and modification of a PEtab problem and currently 20 example parameter estimation problems based on recent studies. Specifications of PEtab, the PEtab Python library, as well as links to examples, and all supporting software tools are available at https://github.com/PEtab-dev/PEtab, a snapshot is available at https://doi.org/10.5281/zenodo.3732958. All original content is available under permissive licenses

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Undergraduate Geography Students Define Aesthetic Maps

Several aesthetic map definition approaches aim to describe the components, concepts and aspects of aesthetic maps. While the discussion is mostly conducted by mapping professionals and researchers, one may wonder how naïve map users would define an aesthetic map. Thirty-four undergraduate geography students answered a short questionnaire in which they defined an aesthetic map, and identified the most aesthetic map along with the reasons why they liked that particular map. Preliminary findings indicate that two important concepts for aesthetic maps are clarity and being visually pleasing/attractive. Favorite aesthetic maps ranged widely from reference to thematic to imaginary maps. Questionnaire results also indicate the emerging importance of and possible aesthetic paradigm shift towards mobile and other interactive, web-based spatial representations. Naïve aesthetic map definitions could provide an important insight into current and future aesthetic map trends

Multiple Hotlink Assignment

The input for the hotlink assignment problem consists of a node weighted directed acyclic graph with a designated root node r. The goal is to minimize the weighted shortest path length rooted at r by adding a restricted number of outgoing arcs (hotlinks) to each node

Geoinformation Technologies to Support Collaborative Emergency Management

In today’s emergency management environments geoinformation technologies play a vital role, but their potential has not been fully exploited. Key decision makers usually do not have direct access to Geographic Information Systems and if they receive access, complex user interfaces often hinder performance for high pressure tasks. In order to provide decision makers with direct and easy access to geoinformation in emergency situations and support group collaboration, we developed three collaborative geoinformation platforms: the Multimodal Interface Platform for Geographic Information Systems (GeoMIP), the GeoCollaborative Crisis Management platform for mobile collaboration and a web-portal for humanitarian relief logistics. The technologies developed are intelligent, multimodal (speech and gesture-based) user interfaces that allow synchronous and asynchronous collaboration between decision makers; support GIS use by mobile emergency management teams; and provide open standards-based web portal technologies

Wasserstein Perturbations of Markovian Transition Semigroups

Fuhrmann S, Kupper M, Nendel M. Wasserstein Perturbations of Markovian Transition Semigroups. Center for Mathematical Economics Working Papers. Vol 649. Bielefeld: Center for Mathematical Economics; 2021.In this paper, we deal with a class of time-homogeneous continuous-time Markov processes with transition probabilities bearing a nonparametric uncertainty. The uncertainty is modelled by considering perturbations of the transition probabilities within a proximity in Wasserstein distance. As a limit over progressively finer time periods, on which the level of uncertainty scales proportionally, we obtain a convex semigroup satisfying a nonlinear PDE in a viscosity sense. A remarkable observation is that, in standard situations, the nonlinear transition operators arising from nonparametric uncertainty coincide with the ones related to parametric drift uncertainty. On the level of the generator, the uncertainty is reflected as an additive perturbation in terms of a convex functional of first order derivatives. We additionally provide sensitivity bounds for the convex semigroup relative to the reference model. The results are illustrated with Wasserstein perturbations of Lévy processes, infinite-dimensional Ornstein-Uhlenbeck processes, geometric Brownian motions, and Koopman semigroups.AMS 2020 Subject Classification: Primary 60J35; 47H20; Scondary 60G65; 90C31; 62G3