Innate NKT lymphocytes confer superior adaptive immunity via tumor-capturing dendritic cells

If irradiated tumor cells could be rendered immunogenic, they would provide a safe, broad, and patient-specific array of antigens for immunotherapies. Prior approaches have emphasized genetic transduction of live tumor cells to express cytokines, costimulators, and surrogate foreign antigens. We asked if immunity could be achieved by delivering irradiated, major histocompatibility complex-negative plasmacytoma cells to maturing mouse dendritic cells (DCs) within lymphoid organs. Tumor cells injected intravenously (i.v.) were captured by splenic DCs, whereas subcutaneous (s.c.) injection led only to weak uptake in lymph node or spleen. The natural killer T (NKT) cells mobilizing glycolipid α-galactosyl ceramide, used to mature splenic DCs, served as an effective adjuvant to induce protective immunity. This adjuvant function was mimicked by a combination of poly IC and agonistic αCD40 antibody. The adjuvant glycolipid had to be coadministered with tumor cells i.v. rather than s.c. Specific resistance was generated both to a plasmacytoma and lymphoma. The resistance afforded by a single vaccination lasted \u3e2 mo and required both CD4+ and CD8+ T cells. Mature tumor capturing DCs stimulated the differentiation of P1A tumor antigen-specific, CD8+ T cells and uniquely transferred tumor resistance to naive mice. Therefore, the access of dying tumor cells to DCs that are maturing to activated NKT cells efficiently induces long-lived adaptive resistance

The CD8+ dendritic cell subset selectively endocytoses dying cells in culture and in vivo

Dendritic cells (DCs) are able in tissue culture to phagocytose and present antigens derived from infected, malignant, and allogeneic cells. Here we show directly that DCs in situ take up these types of cells after fluorescent labeling with carboxyfluorescein succinimidyl ester (CFSE) and injection into mice. The injected cells include syngeneic splenocytes and tumor cell lines, induced to undergo apoptosis ex vivo by exposure to osmotic shock, and allogeneic B cells killed by NK cells in situ. The CFSE-labeled cells in each case are actively endocytosed by DCs in vivo, but only the CD8+ subset. After uptake, all of the phagocytic CD8+ DCs can form major histocompatibility complex class II-peptide complexes, as detected with a monoclonal antibody specific for these complexes. The CD8+ DCs also selectively present cell-associated antigens to both CD4+ and CD8+ T cells. Similar events take place with cultured DCs; CD8+ DCs again selectively take up and present dying cells. In contrast, both CD8+ and CD8- DCs phagocytose latex particles in culture, and both DC subsets present soluble ovalbumin captured in vivo. Therefore CD8+ DCs are specialized to capture dying cells, and this helps to explain their selective ability to cross present cellular antigens to both CD4+ and CD8+ T cells

Immune tolerance after delivery of dying cells to dendritic cells in situ

Peripheral immune tolerance is believed to be induced by the processing and presentation of self-tissues that die during physiologic tissue turnover. To examine the mechanism that mediates tolerance, we injected mice with dying syngeneic TAP-/- splenocytes loaded with small amounts of the protein antigen, ovalbumin (OVA). After ingestion and presentation of cell-associated OVA by the CD8+ subset of dendritic cells in situ, large numbers of antigen-reactive, CD8+ T cell receptor (TCR) transgenic T lymphocytes were driven into cell cycle, but then the T cells were deleted. The animals were also tolerant to challenge with OVA in complete Freund\u27s adjuvant. An agonistic anti-CD40 monoclonal antibody was then administered together with the OVA-loaded splenocytes, so that the dendritic cells in the recipient mice would mature. In contrast to observations made in the steady state, the antigen-reactive T cells expanded in numbers for 1-2 wk and produced large amounts of interleukin 2 and interferon γ, while the animals retained responsiveness to antigen rechallenge. The specific tolerance that develops when dendritic cells process self tissues in the steady state should prevent or reduce the development of autoimmunity when dying cells are subsequently processed during infection

Thermodynamics of Ion Separation by Electrosorption

We present a simple, top-down approach for the calculation of minimum energy consumption of electrosorptive ion separation using variational form of the (Gibbs) free energy. We focus and expand on the case of electrostatic capacitive deionization (CDI), and the theoretical framework is independent of details of the double-layer charge distribution and is applicable to any thermodynamically consistent model, such as the Gouy-Chapman-Stern (GCS) and modified Donnan (mD) models. We demonstrate that, under certain assumptions, the minimum required electric work energy is indeed equivalent to the free energy of separation. Using the theory, we define the thermodynamic efficiency of CDI. We explore the thermodynamic efficiency of current experimental CDI systems and show that these are currently very low, less than 1% for most existing systems. We applied this knowledge and constructed and operated a CDI cell to show that judicious selection of the materials, geometry, and process parameters can be used to achieve a 9% thermodynamic efficiency (4.6 kT energy per removed ion). This relatively high value is, to our knowledge, by far the highest thermodynamic efficiency ever demonstrated for CDI. We hypothesize that efficiency can be further improved by further reduction of CDI cell series resistances and optimization of operational parameters

The effects of residential area building layout on outdoor wind environment at the pedestrian level in severe cold regions of China

In recent years, there has been a frequent occurrence of extremely cold conditions which has had a serious impact on the life of residents of buildings in various locations around the world. However, there have only been a very limited number of studies on the effects of residential area building layout on the winter wind environments, which led to a lack of quantitative guidance for residential area planning in severely cold regions. This study aims to reveal the relationship between (1) the residential areas' building density, floor area ratio, wind projection angle, average building height, and relative position of high-rise buildings, and; (2) the mean wind velocity ratio at pedestrian level in severe cold regions. In this study, the pedestrian-level outdoor wind environments in 24 typical residential areas of Harbin, China, are simulated using ENVI-met software. The results show that the relative position of high-rise buildings in multi-high-level mixed residential areas has little influence on the mean wind velocity ratio, and the maximum difference is 0.04. The factors of building layout have little influence on the mean wind velocity ratio of multistory residential areas. However, a significant linear correlation exists between the mean wind velocity ratio of high-rise residential areas and both the building density and wind projection angle. The prediction model of the mean pedestrian-level wind velocity ratio was then established

Overall effects of temperature steps in hot summer on students' subjective perception, physiological response and learning performance

University students are very likely to experience temperature steps before class in hot summer. This study aims to investigate the overall effects of step changes on students' subjective perception, physiological response and learning performance, so as to explore an optimal thermal condition for classrooms in hot summer. Four typical temperature step conditions (S6: 34 °C-28 °C, S8: 34 °C-26 °C, S10: 34 °C-24 °C, S12: 34 °C–22 °C) were developed to conduct experiments on sixteen participants. It has been found that after temperature steps, no more than 62.5% of students consistently found thermally acceptable at 22 °C; students felt the most acceptable and comfortable at 26 °C; the effect of thermal environment on workload was not significant in most cases, especially for memory-related tasks; students' negative mood was less at 26 °C than at 28 °C and 22 °C. When the temperature step was less than S12, blood pressure and blood oxygen saturation were insensitive to temperature steps; core temperature continued to rise during the first 5 min and then decreased significantly when the temperature step exceeded S8. No significant difference in learning performance was found among the four conditions; the differences in relative performance between thermal conditions were <2%, and are not likely to have practical meaning in building management practice. Overall, the optimal thermal condition is 26 °C, and it is recommended to set the indoor temperature between 24 and 28 °C

The linkage of innate to adaptive immunity via maturing dendritic cells in vivo requires CD40 ligation in addition to antigen presentation and CD80/86 costimulation

Dendritic cell (DC) maturation is an innate response that leads to adaptive immunity to coadministered proteins. To begin to identify underlying mechanisms in intact lymphoid tissues, we studied α-galactosylceramide. This glycolipid activates innate Vα14+ natural killer T cell (NKT) lymphocytes, which drive DC maturation and T cell responses to ovalbumin antigen. Hours after giving glycolipid i.v., tumor necrosis factor (TNF)-α and interferon (IFN)-γ were released primarily by DCs. These cytokines induced rapid surface remodeling of DCs, including increased CD80/86 costimulatory molecules. Surprisingly, DCs from CD40-/- and CD40L-/- mice did not elicit CD4+ and CD8+ T cell immunity, even though the DCs exhibited presented ovalbumin on major histocompatibility complex class I and II products and expressed high levels of CD80/86. Likewise, an injection of TNF-α up-regulated CD80/86 on DCs, but CD40 was required for immunity. CD40 was needed for DC interleukin (IL)-12 production, but IL-12p40-/- mice generated normal ovalbumin-specific responses. Therefore, the link between innate and adaptive immunity via splenic DCs and innate NKT cells has several components under distinct controls: antigen presentation in the steady state, increases in costimulatory molecules dependent on inflammatory cytokines, and a distinct CD40/CD40L signal that functions together with antigen presentation ( signal one ) and costimulation ( signal two ) to generate functioning CD4+ T helper cell 1 and CD8+ cytolytic T lymphocytes

Exploiting Full/Half-Duplex User Relaying in NOMA Systems

In this paper, a novel cooperative non-orthogonal multiple access (NOMA) system is proposed, where one near user is employed as decode-and-forward (DF) relaying switching between full-duplex (FD) and half-duplex (HD) mode to help a far user. Two representative cooperative relaying scenarios are investigated insightfully. The \emph{first scenario} is that no direct link exists between the base station (BS) and far user. The \emph{second scenario} is that the direct link exists between the BS and far user. To characterize the performance of potential gains brought by FD NOMA in two considered scenarios, three performance metrics outage probability, ergodic rate and energy efficiency are discussed. More particularly, we derive new closed-form expressions for both exact and asymptotic outage probabilities as well as delay-limited throughput for two NOMA users. Based on the derived results, the diversity orders achieved by users are obtained. We confirm that the use of direct link overcomes zero diversity order of far NOMA user inherent to FD relaying. Additionally, we derive new closed-form expressions for asymptotic ergodic rates. Based on these, the high signal-to-noise radio (SNR) slopes of two users for FD NOMA are obtained. Simulation results demonstrate that: 1) FD NOMA is superior to HD NOMA in terms of outage probability and ergodic sum rate in the low SNR region; and 2) In delay-limited transmission mode, FD NOMA has higher energy efficiency than HD NOMA in the low SNR region; However, in delay-tolerant transmission mode, the system energy efficiency of HD NOMA exceeds FD NOMA in the high SNR region.Comment: 15 pages,10 figure

Differential Evolution-based 3D Directional Wireless Sensor Network Deployment Optimization

Wireless sensor networks (WSNs) are applied more and more widely in real life. In actual scenarios, 3D directional wireless sensors (DWSs) are constantly employed, thus, research on the real-time deployment optimization problem of 3D directional wireless sensor networks (DWSNs) based on terrain big data has more practical significance. Based on this, we study the deployment optimization problem of DWSNs in the 3D terrain through comprehensive consideration of coverage, lifetime, connectivity of sensor nodes, connectivity of cluster headers and reliability of DWSNs. We propose a modified differential evolution (DE) algorithm by adopting CR-sort and polynomial-based mutation on the basis of the cooperative coevolutionary (CC) framework, and apply it to address deployment problem of 3D DWSNs. In addition, to reduce computation time, we realize implementation of message passing interface (MPI) parallelism. As is revealed by the experimentation results, the modified algorithm proposed in this paper achieves satisfying performance with respect to either optimization results or operation time