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Tumor necrosis factor (TNF) receptor-2 (TNFR2) has attracted considerable interest as a target for immunotherapy. Indeed, using oligomeric fusion proteins of single chain-encoded TNFR2-specific TNF mutants (scTNF80), expansion of regulatory T cells and therapeutic activity could be demonstrated in various autoinflammatory diseases, including graft-versus-host disease (GvHD), experimental autoimmune encephalomyelitis (EAE) and collagen-induced arthritis (CIA). With the aim to improve the in vivo availability of TNFR2-specific TNF fusion proteins, we used here the neonatal Fc receptor (FcRn)-interacting IgG1 molecule as an oligomerizing building block and generated a new TNFR2 agonist with improved serum retention and superior in vivo activity.

Mesenteric lymph nodes (mLNs) are sentinel sites of enteral immunosurveillance and immune homeostasis. Immune cells from the gastrointestinal tract (GIT) are constantly recruited to the mLNs in steady-state and under inflammatory conditions resulting in the induction of tolerance and immune cells activation, respectively. Surgical dissection and transplantation of lymph nodes (LN) is a technique that has supported seminal work to study LN function and is useful to investigate resident stromal and endothelial cell biology and their cellular interactions in experimental disease models. Here, we provide a detailed protocol of syngeneic mLN transplantation and report assays to analyze effective mLN engraftment in congenic recipients. Transplanted mLNs allow to study T cell activation and proliferation in preclinical mouse models. Donor mLNs proved viable and functional after surgical transplantation and regenerated blood and lymphatic vessels. Immune cells from the host completely colonized the transplanted mLNs within 7-8 weeks after the surgical intervention. After allogeneic hematopoietic cell transplantation (allo-HCT), adoptively transferred allogeneic CD4 + T cells from FVB/N (H-2 q ) mice homed to the transplanted mLNs in C57BL/6 (H-2 b ) recipients during the initiation phase of acute graft-versus-host disease (aGvHD). These CD4 + T cells retained full proliferative capacity and upregulated effector and gut homing molecules comparable to those in mLNs from unmanipulated wild-type recipients. Wild type mLNs transplanted into MHCII deficient syngeneic hosts sufficed to activate alloreactive T cells upon allogeneic hematopoietic cell transplantation, even in the absence of MHCII + CD11c + myeloid cells. These data support that orthotopically transplanted mLNs maintain physiological functions after transplantation. The technique of LN transplantation can be applied to study migratory and resident cell compartment interactions in mLNs as well as immune reactions from and to the gut under inflammatory and non-inflammatory conditions.

Background: Coronary heart disease contributes much to the burden morbidity and mortality from chronic diseases globally and more than 80% of CVD-related deaths worldwide now occur in low and middle income countries. In India about 30 million adults suffer from cardiovascular disease. Objectives: To assess the knowledge of 3rd year G.N.M. students regarding coronary angiography and evaluate the effectiveness of informational booklet on knowledge regarding coronary angiography. Method: Pre-experimental research design was used for the study. Information booklet is dependent variable and knowledge of student nurses regarding coronary angiography is dependent variable. The setting of the study is at selected Schools of nursing at Vijayapur, Karnataka. Simple random sampling technique is used to select the subjects. The sample size is of 60 students. Result: In pre-test majority of subjects 30 (50%) had an average knowledge; 18 (30%) had poor knowledge and 12 (20%) had good knowledge, where as in post-test 51 (85%) of them had good knowledge and 09 (15%) had poor knowledge. Study also reveals that there is no association between pre-test knowledge and selected Socio demographic variables. Study also reveals that calculated paired‘t’ value (t= 26.48) is greater than tabulated value (t= 1.960). Hence H1 is accepted. This indicates that the gain in knowledge score is statistically significant at P< 0.05 levels. Conclusion: The findings of the study conclude that there is a need for educating the student nurses regarding coronary angiography. It implies that a nursing administrator should take part in developing protocols, standing orders related to design of the educational programmes and strategies for GNM Students regarding Coronary angiography.

Graft-vs.-host disease (GvHD) is a major complication of allogenic hematopoietic stem-cell(HSC) transplantation. GvHD is associated with loss of endothelial thrombomodulin, but the relevance of this for the adaptive immune response to transplanted HSCs remains unknown. Here we show that the protease-activated protein C (aPC), which is generated by thrombomodulin, ameliorates GvHD aPC restricts allogenic T-cell activation via the protease activated receptor (PAR)2/PAR3 heterodimer on regulatory T-cells (T regs , CD4 + FOXP3 + ). Preincubation of pan T-cells with aPC prior to transplantation increases the frequency of T regs and protects from GvHD. Preincubation of human T-cells (HLA-DR4 − CD4 + ) with aPC prior to transplantation into humanized (NSG-AB°DR4) mice ameliorates graft-vs.-host disease. The protective effect of aPC on GvHD does not compromise the graft vs. leukaemia effect in two independent tumor cell models. Ex vivo preincubation of T-cells with aPC, aPC-based therapies, or targeting PAR2/PAR3 on T-cells may provide a safe and effective approach to mitigate GvHD. Graft-vs.-host disease is a complication of allogenic hematopoietic stem cell transplantation, and is associated with endothelial dysfunction. Here the authors show that activated protein C signals via PAR2/PAR3 to expand T reg cells, mitigating the disease in mice.

[This corrects the article DOI: 10.3389/fimmu.2022.888274.].

Advancing novel immunotherapy strategies requires refined tools in preclinical research to thoroughly assess drug targets, biodistribution, safety, and efficacy. Light sheet fluorescence microscopy (LSFM) offers unprecedented fast volumetric ex vivo imaging of large tissue samples in high resolution. Yet, to date laborious and unstandardized tissue processing procedures have limited throughput and broader applications in immunological research. Therefore, we developed a simple and harmonized protocol for processing, clearing and imaging of all mouse organs and even entire mouse bodies. Applying this Rapid Optical Clearing Kit for Enhanced Tissue Scanning (ROCKETS) in combination with LSFM allowed us to comprehensively study the in vivo biodistribution of an antibody targeting Epithelial Cell Adhesion Molecule (EpCAM) in 3D. Quantitative high-resolution scans of whole organs did not only reveal known EpCAM expression patterns but, importantly, uncovered several new EpCAM-binding sites. We identified gustatory papillae of the tongue, choroid plexi in the brain and duodenal papillae as previously unanticipated locations of high EpCAM expression. Subsequently, we confirmed high EpCAM expression also in human tongue and duodenal specimens. Choroid plexi and duodenal papillae may be considered as particularly sensitive sites due to their importance for liquor production or as critical junctions draining bile and digestive pancreatic enzymes into the small bowel, respectively. These newly gained insights appear highly relevant for clinical translation of EpCAM-addressing immunotherapies. Thus, ROCKETS in combination with LSFM may help to set new standards for preclinical evaluation of immunotherapeutic strategies. In conclusion, we propose ROCKETS as an ideal platform for a broader application of LSFM in immunological research optimally suited for quantitative co-localization studies of immunotherapeutic drugs and defined cell populations in the microanatomical context of organs or even whole mice.

This paper presents an optimization method for solving the Power Economic Dispatch (PED) problem of thermal generation units with multiple fuels and valve point loadings. The proposed optimizer is a variant of Differential Evolution (DE) characterized as a Stud Differential Evolution (SDE), which has been proposed earlier and implemented on a hydrothermal energy system. In SDE, an operator named Stud Crossover (SC) is introduced in the conventional DE during the trial vector updating process. In SC operator, a best vector gives its optimal information to all other population members through mating. The proposed algorithm’s effectiveness to solve Multiple Fuel PED problem, with and without Valve Point Loading Effects (VPLEs), has been validated by testing it on 10 machine multiple fuel standard test systems having 2400 MW, 2500 MW, 2600 MW, and 2700 MW load demands. The results depict the strength of SDE over various other methods in the literature.

Around the world, countries are integrating photovoltaic generating systems to the grid to support climate change initiatives. However, solar power generation is highly uncertain due to variations in solar irradiance level during different hours of the day. Inaccurate modelling of this variability can lead to non-optimal dispatch of system resources. Therefore, accurate characterization of solar irradiance patterns is essential for effective management of renewable energy resources in an electrical power grid. In this paper, the Weibull distribution based probabilistic model is presented for characterization of solar irradiance patterns. Firstly, Weibull distribution is utilized to model inter-temporal variations associated with reference solar irradiance data through moving window averaging technique, and then the proposed model is used for irradiance pattern generation. To achieve continuity of discrete Weibull distribution parameters calculated at different steps of moving window, Generalized Regression Neural Network (GRNN) is employed. Goodness of Fit (GOF) techniques are used to calculate the error between mean and standard deviation of generated and reference patterns. The comparison of GOF results with the literature shows that the proposed model has improved performance. The presented model can be used for power system planning studies where the uncertainty of different resources such as generation, load, network, etc., needs to be considered for their better management.

Acute graft versus host disease (aGvHD) is a life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT) inflicted by alloreactive T cells primed in secondary lymphoid organs (SLOs) and subsequent damage to aGvHD target tissues. In recent years, Treg transfer and/or expansion has emerged as a promising therapy to modulate aGvHD. However, cellular niches essential for fostering Tregs to prevent aGvHD have not been explored. Here, we tested whether and to what extent MHC class II (MHCII) expressed on Ccl19 + fibroblastic reticular cells (FRCs) shape the donor CD4 + T cell response during aGvHD. Animals lacking MHCII expression on Ccl19 -Cre–expressing FRCs (MHCII ΔCcl19 ) showed aberrant CD4 + T cell activation in the effector phase, resulting in exacerbated aGvHD that was associated with significantly reduced expansion of Foxp3 + Tregs and invariant NK T (iNKT) cells. Skewed Treg maintenance in MHCII ΔCcl19 mice resulted in loss of protection from aGvHD provided by adoptively transferred donor Tregs. In contrast, although FRCs upregulated costimulatory surface receptors, and although they degraded and processed exogenous antigens after myeloablative irradiation, FRCs were dispensable to activate alloreactive CD4 + T cells in 2 mouse models of aGvHD. In summary, these data reveal an immunoprotective, MHCII-mediated function of FRC niches in secondary lymphoid organs (SLOs) after allo-HCT and highlight a framework of cellular and molecular interactions that regulate CD4 + T cell alloimmunity.

The transformation of a conventional power system to a smart grid has been underway over the last few decades. A smart grid provides opportunities to integrate smart homes with renewable energy resources (RERs). Moreover, it encourages the residential consumers to regulate their home energy consumption in an effective way that suits their lifestyle and it also helps to preserve the environment. Keeping in mind the techno-economic reasons for household energy management, active participation of consumers in grid operations is necessary for peak reduction, valley filling, strategic load conservation, and growth. In this context, this paper presents an efficient home energy management system (HEMS) for consumer appliance scheduling in the presence of an energy storage system and photovoltaic generation with the intention to reduce the energy consumption cost determined by the service provider. To study the benefits of a home-to-grid (H2G) energy exchange in HEMS, photovoltaic generation is stochastically modelled by considering an energy storage system. The prime consideration of this paper is to propose a hybrid optimization approach based on heuristic techniques, grey wolf optimization, and a genetic algorithm termed a hybrid grey wolf genetic algorithm to model HEMS for residential consumers with the objectives to reduce energy consumption cost and the peak-to-average ratio. The effectiveness of the proposed scheme is validated through simulations performed for a residential consumer with several domestic appliances and their scheduling preferences by considering real-time pricing and critical peak-pricing tariff signals. Results related to the reduction in the peak-to-average ratio and energy cost demonstrate that the proposed hybrid optimization technique performs well in comparison with different meta-heuristic techniques available in the literature. The findings of the proposed methodology can further be used to calculate the impact of different demand response signals on the operation and reliability of a power system.