Tumor vaccination: Chitosan nanoparticles as antigen vehicles to promote tumor-directed T cell responses

Tumor vaccination is a promising approach for treatment of cancer. Tumor vaccines sensitize the immune system to tumor-specific antigens and thus enhance CD8+ T cell responses. This immune response’s potency can be increased by a strategy where nanoparticles act as vehicles leading to more efficient antigen uptake into antigen-presenting cells with chitosan emerging as a promising basic substance. In this study, the potential of antigen-loaded chitosan nanoparticles (CNPs) as delivery systems for inducing a potent CD8+ T cell response was assessed by using the model antigen SIINFEKL. First, uptake of FITC-conjugated antigen-loaded CNPs was verified. Small (approx. 200 nm in diameter) 90/10 CNPs did not show cytotoxic effects on human dendritic cells. Antigen-loaded CNPs did promote a more proinflammatory phenotype in murine and human dendritic cells. MHC-I mediated presentation of SIINFEKL on DC2.4 cells after treatment with SIINFEKL-loaded 90/10 CNPs was demonstrated. Coculturing CD8+ T cells isolated from spleens of OT-1 mice with DC2.4 cells that had been treated with SIINFEKL-loaded 90/10 CNPs led to elevation of activation marker expression on CD8+ T cells. Lastly, the functionality of these OT-1 derived CD8+ T cells activated by coculture with DC2.4 cells after pre-stimulation with 90/10 SIINFEKL CNPs was demonstrated by verifying CD8+ T cell-mediated antigen-specific lysis of PancOVA cells. Overall, the verification of internalization into dendritic cells, demonstration of low cytotoxicity and initiation of a more proinflammatory phenotype in dendritic cells, confirmation of MHC-I mediated antigen presentation and the activation of functionally active CD8+ T cells supports the hypothesis that CNPs are promising vehicles for tumor vaccination. Further studies have to be conducted to assess CNPs in a more clinical setting

D-effects in Toroidally Compactified Type II String Theory

We review exact results obtained for R^4 couplings in maximally supersymmetric type II string theories. These couplings offer a privileged scene to understand the rules of semiclassical calculus in string theory. Upon expansion in weak string coupling, they reveal an infinite sum of non-perturbative e^{-1/g} effects that can be imputed to euclidean D-branes wrapped on cycles of the compactification manifolds. They also shed light on the relation between Dp-branes and D-(p-2)branes, D-strings and (p,q) strings, instanton sums and soliton loops. The latter interpretation takes over in D<=6 in order to account for the e^{-1/g^2} effects, still mysterious from the point of view of instanton calculus. [To appear in the proceedings of the conference "Quantum Aspects of Gauge Theories, Supersymmetry and Unification" held at Neuchatel University, Switzerland, 18-23 September 1997.]Comment: 1+6 pages, neuchatel.sty include

Periodic patterns displace active phase separation

In this work we identify and investigate a novel bifurcation in conserved systems. This secondary bifurcation stops active phase separation in its nonlinear regime. It is then either replaced by an extended, system-filling, spatially periodic pattern or, in a complementary parameter region, by a novel hybrid state with spatially alternating homogeneous and periodic states. The transition from phase separation to extended spatially periodic patterns is hysteretic. We show that the resulting patterns are multistable, as they show stability beyond the bifurcation for different wavenumbers belonging to a wavenumber band. The transition from active phase separation to the hybrid states is continuous. Both transition scenarios are systems-spanning phenomena in particle conserving systems. They are predicted with a generic dissipative model introduced in this work. Candidates for specific systems, in which these generic secondary transitions are likely to occur, are, for example, generalized models for motility-induced phase separation in active Brownian particles, models for cell division or chemotactic systems with conserved particle dynamics.Comment: 17 pages, 7 figure

Deciphering the Whisper of Volcanoes: Monitoring Velocity Changes at Kamchatka's Klyuchevskoy Group With Fluctuating Noise Fields

Volcanic inflation and deflation often precede eruptions and can lead to seismic velocity changes (dv/v $dv/v$) in the subsurface. Recently, interferometry on the coda of ambient noise‐cross‐correlation functions yielded encouraging results in detecting these changes at active volcanoes. Here, we analyze seismic data recorded at the Klyuchevskoy Volcanic Group in Kamchatka, Russia, between summer of 2015 and summer of 2016 to study signals related to volcanic activity. However, ubiquitous volcanic tremors introduce distortions in the noise wavefield that cause artifacts in the dv/v $dv/v$ estimates masking the impact of physical mechanisms. To avoid such instabilities, we propose a new technique called time‐segmented passive image interferometry. In this technique, we employ a hierarchical clustering algorithm to find periods in which the wavefield can be considered stationary. For these periods, we perform separate noise interferometry studies. To further increase the temporal resolution of our results, we use an AI‐driven approach to find stations with similar dv/v $dv/v$ responses and apply a spatial stack. The impacts of snow load and precipitation dominate the resulting dv/v $dv/v$ time series, as we demonstrate with the help of a simple model. In February 2016, we observe an abrupt velocity drop due to the M7.2 Zhupanov earthquake. Shortly after, we register a gradual velocity increase of about 0.3% at Bezymianny Volcano coinciding with surface deformation observed using remote sensing techniques. We suggest that the inflation of a shallow reservoir related to the beginning of Bezymianny's 2016/2017 eruptive cycle could have caused this local velocity increase and a decorrelation of the correlation function coda

Using singular perturbation theory to determine kinetic parameters in a non-standard coupled enzyme assay

We investigate how to characterize the kinetic parameters of an aminotransaminase using a non-standard coupled (or auxiliary) enzyme assay, where the peculiarity arises for two reasons. First, one of the products of the auxiliary enzyme is a substrate for the primary enzyme and, second, we explicitly account for the reversibility of the auxiliary enzyme reaction. Using singular perturbation theory, we characterize the two distinguished asymptotic limits in terms of the strength of the reverse reaction, which allows us to determine how to deduce the kinetic parameters of the primary enzyme for a characterized auxiliary enzyme. This establishes a parameter-estimation algorithm that is applicable more generally to similar reaction networks. We demonstrate the applicability of our theory by performing enzyme assays to characterize a novel putative aminotransaminase enzyme, CnAptA (UniProtKB Q0KEZ8) from Cupriavidus necator H16, for two different omega-amino acid substrates

Non-Detection of Gravitationally Redshifted Absorption Lines in the X-ray Burst Spectra of GS 1826-24

During a 200 ks observation with the XMM-Newton Reflection Grating Spectrometer, we detected 16 type-I X-ray bursts from GS 1826-24. We combined the burst spectra in an attempt to measure the gravitational redshifts from the surface of the neutron star. We divided the composite GS 1826-24 burst spectrum into three groups based on the blackbody temperature during the bursts. The spectra do not show any obvious discrete absorption lines. We compare our observations with those of EXO 0748-676.Comment: 4 pages, 4 figures; accepted for publication in ApJ