CD4+ T Cell–Mediated Tumor Rejection Involves Inhibition of Angiogenesis that Is Dependent on IFNγ Receptor Expression by Nonhematopoietic Cells

AbstractImmunity against MHC class II− tumors can be mediated by CD4+ T cells in the effector phase through an unknown mechanism. We show that this is IFNγ dependent but does not require IFNγ receptor (IFNγR) expression on tumor cells, T cells, or other hematopoietic cells and that IFNγR expression is not necessary in the priming phase. However, tumor immunity requires IFNγR expression on nonhematopoietic cells in the effector phase and involves inhibition of tumor-induced angiogenesis. This shows that an effective anti-tumor response involves communication between CD4+ T cells and nonhematopoietic cells, most likely within the tumor stroma, and that tumor immunity must not entirely rely on direct tumor cell killing

Fine-Granularity Transmission Distortion Modeling for Video Packet Scheduling Over Mesh Networks

Digital Object Identifier 10.1109/TMM.2009.2036290Packet scheduling is a critical component in multi-session video streaming over mesh networks. Different video packets have different levels of contribution to the overall video presentation quality at the receiver side. In this work, we develop a fine-granularity transmission distortion model for the encoder to predict the quality degradation of decoded videos caused by lost video packets. Based on this packet-level transmission distortion model, we propose a content-and-deadline-aware scheduling (CDAS) scheme for multi-session video streaming over multi-hop mesh networks, where content priority, queuing delays, and dynamic network transmission conditions are jointly considered for each video packet. Our extensive experimental results demonstrate that the proposed transmission distortion model and the CDAS scheme significantly improve the performance of multi-session video streaming over mesh networks

Tumor Rejection by Disturbing Tumor Stroma Cell Interactions

The stroma of solid tumors is a complex network of different cell types. We analyzed stroma cell interactions in two tumor models during cyclophosphamide (Cy)-induced tumor rejection. In growing tumors, tumor infiltrating macrophages (TIMs) produced interleukin (IL)-10. Beginning 6 h after Cy-treatment T cells in the tumor were inactivated and TIMs switched to interferon (IFN)-γ production. Both, IL-10 production before and IFN-γ production after Cy-treatment by TIMs required T cells. With the same kinetics as TIMs started to produce IFN-γ the tumor vasculature was destroyed which required IFN-γ receptor expression on host but not tumor cells. These events preceded hemorrhagic necrosis and residual tumor cell elimination by T cells. Together, T cells regulate the function of TIMs and tumor rejection can be induced by disturbing the stroma network

T Helper Cell Type 1–associated and Cytotoxic T Lymphocyte–mediated Tumor Immunity Is Impaired in Interleukin 4–deficient Mice

It is widely accepted that cellular immune responses are induced by CD4+ T helper 1 (Th1) cells secreting interleukin (IL)-2 and interferon (IFN)-γ. Tumor immunity is often mediated by cytotoxic T lymphocytes (CTLs) whose activation is supported by Th1 cytokines. Since IL-4 directs Th2 development and has been shown to inhibit Th1-dominated responses, we assumed that IL-4–deficient (IL-4−/−) mice would develop vigorous CTL-mediated tumor immunity compared with IL-4–competent (IL-4+/+) mice. Surprisingly, IL-4−/− mice were severely impaired to develop tumor immunity to both a mammary adenocarcinoma line and a colon carcinoma line. The lack of tumor immunity in IL-4−/− mice was associated with reduced IFN-γ production, diminished levels of tumor-reactive serum IgG2a, and undetectable CTL activity, indicating a defective Th1 response in the absence of endogenous IL-4. Anti–IL-4 monoclonal antibody blocked tumor immunity in IL-4+/+ mice when administered at the time of immunization but not at the time of challenge. Additionally, tumor immunity could be induced in IL-4−/− mice, if IL-4 was provided by gene-modified cells together with immunizing tumor cells. These results demonstrate that tumor immunity requires IL-4 in the priming phase for the generation of effector cells rather than for their maintenance and exclude secondary, developmental defects in the “knockout” strain. Together, our results demonstrate a novel and previously unanticipated role of IL-4 for the generation of Th1-associated, CTL-mediated tumor immunity

Jointly-Learnt Networks for Future Action Anticipation Via Self-Knowledge Distillation and Cycle Consistency

Future action anticipation aims to infer future actions from the observation of a small set of past video frames. In this paper, we propose a novel Jointly learnt Action Anticipation Network (J-AAN) via Self-Knowledge Distillation (Self-KD) and cycle consistency for future action anticipation. In contrast to the current state-of-the-art methods which anticipate the future actions either directly or recursively, our proposed J-AAN anticipates the future actions jointly in both direct and recursive ways. However, when dealing with future action anticipation, one important challenge to address is the future\u27s uncertainty since multiple action sequences may come from or be followed by the same action. Training an action anticipation model with one-hot-encoded hard labels that assign zero probabilities to incorrect, yet semantically similar actions may not handle the uncertain future. To address this challenge, we design a Self-KD mechanism to train our J-AAN, where the J-AAN gradually distills its own knowledge during the training to soften the hard labels to model the uncertainty on future action anticipation. Furthermore, we design a forward and backward action anticipation framework with our proposed J-AAN based on a cyclic consistency constraint. The forward J-AAN anticipates the future actions from the observed past actions, and the backward J-AAN verifies the anticipation of the forward J-AAN by anticipating the past actions from the anticipated future actions. The proposed method outperforms all the latest state-of-the-art action anticipation methods on the breakfast, 50Salads, and EPIC-Kitchens-55 datasets. This project will be publicly available on https://github.com/MoniruzzamanMd/J-AAN

All-fiber probing of aluminized RDX particle micro-explosion

Investigating the thermal decomposition characteristics and mechanisms of nano- and submicron-aluminized 1,3,5-trinitro-1,3,5-triazine (RDX) is essential to optimize the formulations and improve combustion/detonation efficiencies. However, no research has focused on the microscopic scale of a single aluminized RDX particle. We demonstrate an all-fiber probing method for the violent thermal decomposition of a single nano-aluminized micron-RDX particle, which we address as micro-explosion in this paper. We believe studying micro-explosion will be beneficial to the research of thermal decomposition. In experiments, we first characterize the micro-explosion as a three-step process, i.e., melting, first decomposition, and second decomposition. Then, we measure micro-explosion properties, i.e., shockwave-like flow velocity, initiation energy threshold, and shockwave-like flow pressure. Among the aluminized RDX particles with 0%, 5%, 10%, 15%, 20%, 25%, and 30% surface coverage ratios (SCRs), the sample with 20% surface coverage ratio shows the highest flow velocity and force, which are about 69.9 mm/s and 39.4 μN, respectively. Moreover, the threshold decreases with rising surface coverage ratios, and the mean threshold of 30% surface coverage ratio is 75 μJ. The experimental results prove that the all-fiber micro-explosion probing method is feasible, safe, and robust

Loss of Conformational Stability in Calmodulin upon Methionine Oxidation

We have used electrospray ionization mass spectrometry (ESI-MS), circular dichroism (CD), and fluorescence spectroscopy to investigate the secondary and tertiary structural consequences that result from oxidative modification of methionine residues in wheat germ calmodulin (CaM), and prevent activation of the plasma membrane Ca-ATPase. Using ESI-MS, we have measured rates of modification and molecular mass distributions of oxidatively modified CaM species (CaMox) resulting from exposure to H2O2. From these rates, we find that oxidative modification of methionine to the corresponding methionine sulfoxide does not predispose CaM to further oxidative modification. These results indicate that methionine oxidation results in no large-scale alterations in the tertiary structure of CaMox, because the rates of oxidative modification of individual methionines are directly related to their solvent exposure. Likewise, CD measurements indicate that methionine oxidation results in little change in the apparent α-helical content at 28°C, and only a small (0.3 ± 0.1 kcal mol−1) decrease in thermal stability, suggesting the disruption of a limited number of specific noncovalent interactions. Fluorescence lifetime, anisotropy, and quenching measurements of N-(1-pyrenyl)-maleimide (PMal) covalently bound to Cys26 indicate local structural changes around PMal in the amino-terminal domain in response to oxidative modification of methionine residues in the carboxyl-terminal domain. Because the opposing globular domains remain spatially distant in both native and oxidatively modified CaM, the oxidative modification of methionines in the carboxyl-terminal domain are suggested to modify the conformation of the amino-terminal domain through alterations in the structural features involving the interdomain central helix. The structural basis for the linkage between oxidative modification and these global conformational changes is discussed in terms of possible alterations in specific noncovalent interactions that have previously been suggested to stabilize the central helix in CaM

The Reading Palaeofire Database : an expanded global resource to document changes in fire regimes from sedimentary charcoal records

Sedimentary charcoal records are widely used to reconstruct regional changes in fire regimes through time in the geological past. Existing global compilations are not geographically comprehensive and do not provide consistent metadata for all sites. Furthermore, the age models provided for these records are not harmonised and many are based on older calibrations of the radiocarbon ages. These issues limit the use of existing compilations for research into past fire regimes. Here, we present an expanded database of charcoal records, accompanied by new age models based on recalibration of radiocarbon ages using IntCal20 and Bayesian age-modelling software. We document the structure and contents of the database, the construction of the age models, and the quality control measures applied. We also record the expansion of geographical coverage relative to previous charcoal compilations and the expansion of metadata that can be used to inform analyses. This first version of the Reading Palaeofire Database contains 1676 records (entities) from 1480 sites worldwide. The database (RPDv1b - Harrison et al., 2021) is available at https://doi.org/10.17864/1947.000345.Peer reviewe