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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative option for patients with hematological disorders and bone marrow (BM) failure syndromes. Graft-versus-host disease (GVHD) remains a leading cause of morbidity posttransplant. Regulatory T cell (Treg) therapies are efficacious in ameliorating GVHD but limited by variable suppressive capacities and the need for a high therapeutic dose. Here, we sought to expand Treg in vivo by expressing an orthogonal interleukin 2 receptor β (oIL-2Rβ) that would selectively interact with oIL-2 cytokine and not wild-type (WT) IL-2. To test whether the orthogonal system would preferentially drive donor Treg expansion, we used a murine major histocompatibility complex–disparate GVHD model of lethally irradiated BALB/c mice given T cell–depleted BM from C57BL/6 (B6) mice alone or together with B6Foxp3+GFP+ Treg or oIL-2Rβ–transduced Treg at low cell numbers that typically do not control GVHD with WT Treg. On day 2, B6 activated T cells (Tcons) were injected to induce GVHD. Recipients were treated with phosphate-buffered saline (PBS) or oIL-2 daily for 14 days, then 3 times weekly for an additional 14 days. Mice treated with oIL-2Rβ Treg and oIL-2 compared with those treated with PBS had enhanced GVHD survival, in vivo selective expansion of Tregs, and greater suppression of Tcon expansion in secondary lymphoid organs and intestines. Importantly, oIL-2Rβ Treg maintained graft-versus-tumor (GVT) responses in 2 distinct tumor models (A20 and MLL-AF9). These data demonstrate a novel approach to enhance the efficacy of Treg therapy in allo-HSCT using an oIL-2/oIL-2Rβ system that allows for selective in vivo expansion of Treg leading to GVHD protection and GVT maintenance.

Natural Killer (NK) cells are a major subset of innate immune cells that are essential for host defense against pathogens and cancer. Two main classes of inhibitory NK receptors (NKR), KIR and CD94/NKG2A, play a key role in suppressing NK activity upon engagement with tumor cells or virus infected cells, limiting their antitumor and antiviral activity. Here, we find that single-chain mouse NKR antagonists linked to a VHH that binds the cell surface phosphatase CD45 potentiate NK and T activity to a greater extent than NKR blocking antibodies alone in vitro. We also uncovered crosstalk between mouse NKG2A and Ly49 that collectively inhibit NK cell activation, such that CD45-NKG2A and CD45-Ly49 bispecific molecules show synergistic effects in their ability to enhance NK cell activation. The basis of the activity enhancement by CD45 ligation may reflect greater antagonism of inhibitory signaling from engagement of MHC I on target cells, combined with other mechanisms, including avidity effects, tonic signaling, antagonism of weak inhibition from engagement of MHC I on non-target cells and possibly CD45 segregation within the NK cell-target cell synapse. These engineered ligands uncover a mechanism for enhancing the activity of mouse NK and T cells that merits evaluation in the context of human NKR antagonist cancer immunotherapies.

Detecting the early degradation of concrete structures can assist agencies in forecasting and planning future resource demands. Structural defects network SDNET2018 classes were used to create a custom binary convolutional neural network CNN classifier with physical crack damage predictive accuracy of 99.2%. Second, concrete's physical, chemical, and reinforcement damage classes, including a negative class, are stratified to generate a separate dataset using concrete defect bridge image CODEBRIM cropped image database to train a multiclass image classifier model with predictive accuracy of 80%. Comparisons were made based on the computational efficiency of a CNN architecture-specific classifier model and a ResNet50-retrained transfer-learning model predicting at 87.45% accuracy. These findings enable the generalisation and improvement of the damage assessment accuracy of concrete structures., Paper 125

Several effective methods have been developed recently to demonstrate simultaneous high energy and high power density in Li - carbon fluoride (CF$_x$) batteries. These methods can achieve as high as 1000 Wh/kg energy density at 60-70 kW/kg power density (40-50 C rate) in coin cells and 750 Wh/kg energy density at 12.5 kW/kg power density (20 C rate) in pouch cells. This performance is made possible by ingenious nano-architecture design, controlled porosity, boron doping and electrolyte additives. In the present study, we show that a similarly great performance, 931 Wh/kg energy density at 59 kW/kg power density, can be achieved by using a polyacrylonitrile binder and a LiBF4 electrolyte in Li - graphite fluoride coin cells. We also demonstrate that the observed effect is the result of the right combination of the binder and the electrolyte. We propose that the mechanistic origin of the observed phenomena is an electro-catalytic effect by the polyacrylonitrile binder. While our proposed method has a competitive performance, it also offers a simple implementation and a scalable production of high energy and high power primary Li-CF$_x$ cells., Comment: 13 pages, 8 figures, 1 table

Contains fulltext : 290191.pdf (Publisher’s version ) (Open Access) 06 januari 2023

Clinical trials utilizing regulatory T cell (Treg) therapy in organ transplantation have shown promising results, however, the choice of a standard immunosuppressive regimen is still controversial. Calcineurin inhibitors (CNIs) are one of the most common immunosuppressants for organ transplantation, although they may negatively affect Tregs by inhibiting IL-2 production by conventional T cells. As a strategy to replace IL-2 signaling selectively in Tregs, we have introduced an engineered orthogonal IL-2 (ortho IL-2) cytokine/cytokine receptor (R) pair that specifically binds with each other but does not bind with their wild-type counterparts. Murine Tregs were isolated from recipients and retrovirally transduced with ortho IL-2Rβ during ex vivo expansion. Transduced Tregs (ortho Tregs) were transferred into recipient mice in a mixed hematopoietic chimerism model with tacrolimus administration. Ortho IL-2 treatment significantly increased the ortho IL-2Rβ(+) Treg population in the presence of tacrolimus without stimulating other T cell subsets. All the mice treated with tacrolimus plus ortho IL-2 achieved heart allograft tolerance, even after tacrolimus cessation, whereas those receiving tacrolimus treatment alone did not. These data demonstrate that Treg therapy can be adopted into a CNI-based regimen by utilizing cytokine receptor engineering.

Synthetic receptor signalling has the potential to endow adoptively transferred T cells with new functions that overcome major barriers in the treatment of solid tumours, including the need for conditioning chemotherapy1,2. Here we designed chimeric receptors that have an orthogonal IL-2 receptor extracellular domain (ECD) fused with the intracellular domain (ICD) of receptors for common γ-chain (γc) cytokines IL-4, IL-7, IL-9 and IL-21 such that the orthogonal IL-2 cytokine elicits the corresponding γccytokine signal. Of these, T cells that signal through the chimeric orthogonal IL-2Rβ-ECD–IL-9R-ICD (o9R) are distinguished by the concomitant activation of STAT1, STAT3 and STAT5 and assume characteristics of stem cell memory and effector T cells. Compared to o2R T cells, o9R T cells have superior anti-tumour efficacy in two recalcitrant syngeneic mouse solid tumour models of melanoma and pancreatic cancer and are effective even in the absence of conditioning lymphodepletion. Therefore, by repurposing IL-9R signalling using a chimeric orthogonal cytokine receptor, T cells gain new functions, and this results in improved anti-tumour activity for hard-to-treat solid tumours.

Background Several inflammatory cytokines are upregulated in severe coronavirus disease 2019 (COVID-19). We compared cytokines in COVID-19 versus influenza to define differentiating features of the inflammatory response to these pathogens and their association with severe disease. Because elevated body mass index (BMI) is a known risk factor for severe COVID-19, we examined the relationship of BMI to cytokines associated with severe disease. Methods Thirty-seven cytokines and chemokines were measured in plasma from 135 patients with COVID-19, 57 patients with influenza, and 30 healthy controls. Controlling for BMI, age, and sex, differences in cytokines between groups were determined by linear regression and random forest prediction was used to determine the cytokines most important in distinguishing severe COVID-19 and influenza. Mediation analysis was used to identify cytokines that mediate the effect of BMI and age on disease severity. Results Interleukin-18 (IL-18), IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) were significantly increased in COVID-19 versus influenza patients, whereas granulocyte macrophage colony-stimulating factor, interferon-γ (IFN-γ), IFN-λ1, IL-10, IL-15, and monocyte chemoattractant protein 2 were significantly elevated in the influenza group. In subgroup analysis based on disease severity, IL-18, IL-6, and TNF-α were elevated in severe COVID-19, but not in severe influenza. Random forest analysis identified high IL-6 and low IFN-λ1 levels as the most distinct between severe COVID-19 and severe influenza. Finally, IL-1RA was identified as a potential mediator of the effects of BMI on COVID-19 severity. Conclusions These findings point to activation of fundamentally different innate immune pathways in severe acute respiratory syndrome coronavirus 2 and influenza infection, and emphasize drivers of severe COVID-19 to focus both mechanistic and therapeutic investigations.

Applications of silicon as a high-performance anode material have been impeded by its low intrinsic conductivity and huge volume expansion (>300%) during lithiation. To address these problems, nano...

Murine norovirus (MNoV) is a model for human norovirus and for interrogating mechanisms of viral tropism and persistence. We previously demonstrated that the persistent strain MNoV

Background: For over six decades, in many countries, youth fitness testing has been seen as a critical component of physical education programs. As such, preservice physical education teachers (PPE...

This study clarifies, for the first time, that misplacement of Cr3+ ions at the Na+ site plays a more important role in dictating the specific capacity and capacity retention over cycles of O3-NaCr...

Hydrogen energy has been recognized as “Ultimate Power Source” in the 21st century. It is a boon in these days of energy crunches and concerns about climate change because of the characterized advantages, such as high energy density, large calorific value, abundant resource, zero pollution, zero carbon emission, storable and renewable. State-of-the-art perspectives on tuning the stable thermodynamics and sluggish kinetics of dehydrogenation and re-hydrogenation of LiBH4, which has been regarded as a promising hydrogen storage alternative for onboard energy carrier applications have been discussed. Five major technological approaches are involved, including nanoengineering, catalyst modification, ions substitution, reactant destabilization and a novel process termed as high-energy ball milling with in-situ aerosol spraying (BMAS). It is worth noting that BMAS has the potential to help overcome the kinetic barriers for thermodynamically favorable systems like LiBH4 ​+ ​MgH2 mixture and provide thermodynamic driving force to enhance hydrogen release at a lower temperature.

The O3-layered NaCrO2 is a promising Na-ion cathode material with a good thermal stability and specific capacity, but it suffers from a poor rate capability. To develop high-rate Na-ion cathodes, w...

The prediction of hydrogen release ability is indispensable to evaluating hydrogen storage performance of LiBH 4 -based mixtures before experimentation. To achieve this goal, ensemble machine learning is employed to automatically infer the relationship between factors (i.e., sample preparation, mixing conditions and operational variables) and target ( H 2 release amount), providing exceptional insight into hydrogen release ability. Specifically, the importance ranking of major variables for the hydrogen release of LiBH 4 has been proposed for the first time based on the constructed uni-component catalysts database. We train our developed EoE model on 2,071 uni-component catalysts data and attempt to predict the hydrogen release amounts of LiBH 4 doping with the unseen bi-component catalysts. The appealing results demonstrate the effectiveness and robustness of EoE. The procedure established in this study presents a novel approach for accelerating the research and development of hydrogen storage materials over various catalysts.

Various phenomena of life are typically explained by the physical sciences. Although the biological structures of a living being are subject to physical laws, we suggest that life, information, and...

Recent experimental finding has indicated that Fe3B has the capacity to uptake and release hydrogen. However, the mechanism has not been clarified. Here, for the first time, the characteristics were investigated through the electronic structures and energies of H2 molecules adsorbed on Fe3B using density functional theory calculations. Most importantly, this work provides a guideline for experimental investigation of wide-source and low-cost Fe-based hydrogen storage materials.

Chimeric antigen receptor T (CAR-T) cell successes have encouraged continued clinical study. Apheresis collection of starting material for CAR-T cell therapy product manufacturing is critical but described approaches suggest variability and clinical guidelines are currently lacking. The goal of this study was to gather and assess variability in apheresis collection descriptions in publicly available CAR T-cell therapy clinical trials.We searched clinicaltrials.gov (a publicly available clinical trial database) for "chimeric antigen receptor T cells" on July 01, 2020 and studies accessed July 30, 2020-August 15, 2020. Data collected included date posted, study characteristics, apheresis mentions (number, location, and context), laboratory parameters and transfusion allowances. Apheresis context was analyzed using a qualitative inductive approach of grounded theory method with open coding. Text was classified into 37 context codes, grouped into 12 categories, and then consolidated into patient, procedure, product, and miscellaneous themes.Apheresis was mentioned 1044 times in 322 (51.9%) of 621 total studies. Laboratory parameters mentioned included white blood cells (100 studies), absolute neutrophil count (220 studies), absolute lymphocyte count (102 studies), CD3Apheresis collection of CAR-T cell products is not well-defined in clinical study descriptions and the context is inconsistent. Laboratory parameters useful for apheresis collection are variably present and do not consistently align with current practices. Further exploration, and clinical guideline development will encourage alignment of apheresis collections for CAR-T cell products.

Cytokines are powerful immune modulators that initiate signaling through receptor dimerization, but natural cytokines have structural limitations as therapeutics. We present a strategy to discover cytokine surrogate agonists by using modular ligands that exploit induced proximity and receptor dimer geometry as pharmacological metrics amenable to high-throughput screening. Using VHH and scFv to human interleukin-2/15, type-I interferon, and interleukin-10 receptors, we generated combinatorial matrices of single-chain bispecific ligands that exhibited diverse spectrums of functional activities, including potent inhibition of SARS-CoV-2 by surrogate interferons. Crystal structures of IL-2R:VHH complexes revealed that variation in receptor dimer geometries resulted in functionally diverse signaling outputs. This modular platform enabled engineering of surrogate ligands that compelled assembly of an IL-2R/IL-10R heterodimer, which does not naturally exist, that signaled through pSTAT5 on T and natural killer (NK) cells. This “cytokine med-chem” approach, rooted in principles of induced proximity, is generalizable for discovery of diversified agonists for many ligand-receptor systems.

We consider analytically velocity pair structure function of turbulent pulsations on the background of a coherent geostrophic vortex in a fast rotating fluid. The statistics of the turbulent pulsations is determined by their dynamics that is the dynamics of inertial waves affected by the differential rotation in the vortex and weak viscous damping. Our consideration is restricted by the smallest scales, where the velocity field remains smooth. We establish the anisotropy of the structure function. The velocity gradient of the turbulent pulsations achieves its largest value for the nearly radial direction and its smallest value in the nearly streamwise direction. The inclination angle between the directions of extremum values of the gradient and the vortex-associated directions is determined by the interplay between the shear rate and the viscosity influence. The scaling laws resemble their behavior for a passive scalar in a steady shear flow.

The dehydrogenation reaction pathway and rate-limiting step of a nano-LiBH4 + nano-MgH2 mixture with a 0.5:1 molar ratio, which has been shown to have the ability to reversibly release and absorb ∼5.7 wt% H2 at 265 °C, have been investigated in detail. The study reveals that the solid-state dehydrogenation kinetics of the MgH2 + 0.5 LiBH4 mixture at 265 °C is nucleation-and-growth controlled. The rate-limiting step for dehydrogenation via the two parallel reaction pathways has been identified through examination of the elementary reactions as the nucleation and growth of reaction products LiH and MgB2. The interfacial area between MgH2 and LiBH4 plays a critical role in the nucleation and growth of LiH and MgB2, and thus influence the dehydrogenation kinetics and H2 storage capacity of the MgH2 + 0.5 LiBH4 mixture. X-ray diffraction, SEM analysis and specific surface area measurements reveal that the evolution of the powder characteristics before and after isothermal hydrogen uptake/release cycles is consistent with the kinetics observation and analysis. This study indicates that to further improve the dehydrogenation kinetics of the MgH2 + LiBH4 mixture, the nucleation and growth rates of LiH and/or MgB2 should be enhanced in the future, while the interfacial area between MgH2 and LiBH4 should be increased and maintained to be as large as possible during hydrogen uptake/release cycles.

The prospect of LiBH4 + MgH2 mixtures has been limited by their sluggish kinetics despite their excellent hydrogen storage capacity theoretically. This study demonstrates that ball milling with aerosol spraying (BMAS) established in the previous study can not only tune the thermodynamics but also improve the kinetics for hydrogen release from a LiBH4 + MgH2 mixture. The improved thermodynamics has been evaluated from the viewpoint of the significantly heightened dissociation pressure. Nine different kinetics models have been used to analyze the solid-state dehydrogenation behavior of the BMAS powder with 50% LiBH4 at 265 °C. The kinetics analysis reveals that the rate-limiting step of this BMAS powder is initially controlled by the nucleation/growth process but then is changed to moving-phase boundary control and finally to diffusion control as the number of dehydrogenation/rehydrogenation cycles increases. The change in the dehydrogenation kinetics with increasing cycles has been attributed to the presen...

A nano-LiBH4 ​+ ​nano-MgH2 mixture which can reversibly release and absorb ∼5.0 wt% H2 at 265 °C is synthesized via a new processing method, termed as Ball Milling with Aerosol Spraying (BMAS) established in this study. The reversible storage capacity of ∼5.0 wt% H2 is the highest one ever reported for the LiBH4 + MgH2 system at temperature ≤265 °C. It is found that the unusually high reversible hydrogen storage is accomplished through two parallel reaction pathways. One is nano-LiBH4 decomposes to form Li2B12H12 and H2 first and then Li2B12H12 reacts with MgH2 to form MgB2, LiH and H2. The other is nano-MgH2 decomposes to form Mg and H2 first and then Mg reacts with LiBH4 to form MgB2, LiH and H2. These reaction pathways become possible because of the presence of nano-LiBH4 and nano-MgH2 and their intimate mixing, enabled by the BMAS process. This study unambiguously shows that nano-engineering can overcome kinetics barriers for thermodynamically favorable systems like the LiBH4 ​+ ​MgH2 mixture and even provides thermodynamic driving force to enhance hydrogen release at low temperature. The principle established in this study also opens up a new direction for investigating and improving the hydrogenation and dehydrogenation properties of many other systems containing multiple hydride components that have favorable thermodynamic properties for reversible hydrogen storage, but with limited kinetics.

A facile wet-chemical method to coat nano-LiCoO2 particles is investigated and established in this study. In this newly developed wet-chemical method, Al(NO3)3 is used as the Al source to form Al2O...

In this study, Li(Ni1/3Mn1/3Co1/3)O2 (NMC333) and Li(Ni0.5Mn0.3Co0.2)O2 (NMC532) have been subjected to a phosphoric acid (H3PO4) solution treatment to form a thin Li3PO4 coating on their surfaces. The Li3PO4 coating formed is found to be very potent in enhancing the specific capacity of the first discharge as well as the rate capability and capacity retention in the subsequent charge/discharge cycles for both NMC333 and NMC532. The specific capacity of the first discharge for NMC532 has been increased drastically from ∼160 mA h g−1 for pristine NMC532 to ∼250 mA h g−1 for Li3PO4-coated counterpart at 0.1C and such a large capacity enhancement is retained throughout the subsequent cycles at 1C. The final specific capacity of Li3PO4-coated NMC532 is 187 mA h g−1 after 100 cycles at 1C, whereas the corresponding value of pristine NMC532 is only 50 mA h g−1. The rate capability has also been improved significantly with Li3PO4-coated NMC532 exhibiting ∼150 mA h g−1 capacity at 6C while pristine NMC532 showing zero capacity. Similar improvements have also been achieved with NMC333. These results demonstrate that the H3PO4 treatment is a facile and general method to improve the electrochemical properties of NMCs with different compositions and can be utilized for practical applications.

In this study, the long-term cycle behavior of nano-LiCoO2 cathodes over 500 cycles at high rates is investigated. Furthermore, the postmortem analysis of the cycled nano-LiCoO2 cathodes using a combination of X-ray absorption spectroscopy and X-ray diffraction is also conducted to shed light on the capacity decay mechanisms. It is found that crystalline nano-LiCoO2 after 500 charge/discharge cycles at 10C becomes amorphous, exhibits Co2+ species rather than the expected Co3+ at the fully lithiated condition, has longer Co–O bond length than that of pristine nano-LiCoO2 and micro-LiCoO2, and exhibits 53% specific capacity loss over 500 cycles at 10C. In addition, slow Li-ion intercalation and deintercalation at the electrode/electrolyte interface are found to be the rate-limiting step for nano-LiCoO2 during discharge and charge, respectively. Thus, to achieve the high-rate capability of LiCoO2, not only LiCoO2 particle sizes should be reduced to nanoscales but also the Li-ion intercalation and deintercala...

BackgroundSeveral inflammatory cytokines are upregulated in severe COVID-19. We compared cytokines in COVID-19 versus influenza in order to define differentiating features of the inflammatory response to these pathogens and their association with severe disease. Because elevated body mass index (BMI) is a known risk factor for severe COVID-19, we examined the relationship of BMI to cytokines associated with severe disease.MethodsThirty-seven cytokines and chemokines were measured in plasma from 145 patients with COVID-19, 57 patients with influenza, and 30 healthy controls. Controlling for BMI, age, and sex, differences in cytokines between groups were determined by linear regression and random forest prediction was utilized to determine the cytokines most important in distinguishing severe COVID-19 and influenza. Mediation analysis was utilized to identify cytokines that mediate the effect of BMI on disease severity.ResultsIL-18, IL-1β, IL-6, and TNF-α were significantly increased in COVID-19 versus influenza patients while GM-CSF, IFN-γ, IFN-λ1, IL-10, IL-15, and MCP-2 were significantly elevated in the influenza group. In subgroup analysis based on disease severity, IL-18, IL-6, and TNF-α were elevated in severe COVID-19, but not severe influenza. Random forest analysis identified high IL-6 and low IFN-λ1 levels as the most distinct between severe COVID-19 and severe influenza. Finally, IL-1RA was identified as a potential mediator of the effects of BMI on COVID-19 severity.ConclusionsThese findings point to activation of fundamentally different innate immune pathways in SARS-CoV-2 and influenza infection, and emphasize drivers of severe COVID-19 to focus both mechanistic and therapeutic investigations.SummarySevere COVID-19 is marked by dysregulated inflammation and is associated with elevated BMI. By comparing cytokines and chemokines in patients with either COVID-19 or influenza, we identified distinct inflammatory pathways and a cytokine mediator of the effect of BMI.

Since Karl Benz designed and built the first motorized tricycle powered by an internal-combustion engine in 1885, the time of automobiles has begun. From then on, human life was modernized by gasoline-powered vehicles, and cars were labelled as “the machine that changed the world”. Li-ion batteries (LIBs), the key device to power electric vehicles, have attracted attention, enthusiasm and intensive development activity throughout recent years because of their high output voltage, high specific energy, long cycle life and absence of memory effect. The application of LIBs in electric vehicles is at an early stage of development compared to the internal combustion engine in conventional vehicles. Although significant breakthroughs have been made in technologies of LIBs in the past decades, LIBs that can provide higher energy density, lower cost, faster charging ability as well as safer and better performance at low temperature are in constant demand from consumers.

Noroviruses are a leading cause of gastrointestinal infection in humans and mice. Understanding human norovirus (HuNoV) cell tropism has important implications for our understanding of viral pathogenesis. Murine norovirus (MNoV) is extensively used as a surrogate model for HuNoV. We previously identified CD300lf as the receptor for MNoV. Here, we generated a Cd300lf conditional knockout (CD300lf(F/F)) mouse to elucidate the cell tropism of persistent and nonpersistent strains of murine norovirus. Using this mouse model, we demonstrated that CD300lf expression on intestinal epithelial cells (IECs), and on tuft cells in particular, is essential for transmission of the persistent MNoV strain CR6 (MNoV(CR6)) in vivo. In contrast, the nonpersistent MNoV strain CW3 (MNoV(CW3)) does not require CD300lf expression on IECs for infection. However, deletion of CD300lf in myelomonocytic cells (LysM Cre+) partially reduces CW3 viral load in lymphoid and intestinal tissues. Disruption of CD300lf expression on B cells (CD19 Cre), neutrophils (Mrp8 Cre), and dendritic cells (CD11c Cre) did not affect MNoV(CW3) viral RNA levels. Finally, we show that the transcription factor STAT1, which is critical for the innate immune response, partially restricts the cell tropism of MNoV(CW3) to LysM+ cells. Taken together, these data demonstrate that CD300lf expression on tuft cells is essential for MNoV(CR6); that myelomonocytic cells are a major, but not exclusive, target cell of MNoV(CW3); and that STAT1 signaling restricts the cellular tropism of MNoV(CW3). This study provides the first genetic system for studying the cell type-specific role of CD300lf in norovirus pathogenesis. IMPORTANCE Human noroviruses (HuNoVs) are a leading cause of gastroenteritis resulting in up to 200,000 deaths each year. The receptor and cell tropism of HuNoV in immunocompetent humans are unclear. We use murine norovirus (MNoV) as a model for HuNoV. We recently identified CD300lf as the sole physiologic receptor for MNoV. Here, we leverage this finding to generate a Cd300lf conditional knockout mouse to decipher the contributions of specific cell types to MNoV infection. We demonstrate that persistent MNoV(CR6) requires CD300lf expression on tuft cells. In contrast, multiple CD300lf+ cell types, dominated by myelomonocytic cells, are sufficient for nonpersistent MNoV(CW3) infection. CD300lf expression on epithelial cells, B cells, neutrophils, and dendritic cells is not critical for MNoV(CW3) infection. Mortality associated with the MNoV(CW3) strain in Stat1(−/−) mice does not require CD300lf expression on LysM+ cells, highlighting that both CD300lf receptor expression and innate immunity regulate MNoV cell tropism in vivo.

We consider analytically pair structure function of turbulent pulsations on the background of a coherent geostrophic vortex in a fast rotating fluid. The statistics of the turbulent pulsation is determined by their dynamics which is the dynamics of inertia waves affected by the differential rotation in the vortex and weak viscous damping. Our consideration is restricted by the smallest scales, where the velocity field remains smooth. We establish the anisotropy of the structure function. The velocity gradient of the turbulent pulsations achieves its largest value for the radial direction and its smallest value in the streamwise direction, resembling its behaviour in turbulent flow with mean shear component without imposed rotation., Comment: 4 pages, 0 figures

Background: Orthogonal cytokine-receptor pairs allow selective in vivo manipulation of T cells after adoptive cell therapy (ACT) of cancer. Using mouse models, we previously described a chimeric orthogonal receptor (o9R) comprised of an orthogonal IL-2Rβ extracellular domain (ECD) and an IL-9R intracellular domain (ICD). Adoptive transfer of tumor-specific T cells engineered with o9R showed superior anti-tumor activity in mice treated with orthogonal IL-2 (oIL2). To evaluate the translational potential of o9R signaling, we generated and evaluated a human chimeric orthogonal IL-2Rβ ECD/IL-9R ICD (ho9R). Methods: We hypothesized that ho9R in tumor-specific T cells would result in distinct signaling, phenotypic and functional properties compared to the human orthogonal IL-2Rβ (ho2R), mirroring our observations in the mouse system. Activated T cells were retrovirally transduced with two vectors: one encoding either ho9R or ho2R and another encoding a T cell receptor (TCR) specific for NY-ESO-1 in the context of HLA*0201. Transduced and sorted T cells were exposed to mouse serum albumin-bound human orthogonal IL2 (MSA-hoIL2) or wildtype IL-2 (MSA-hIL2) for 20 mins to evaluate STAT-1, -3 and -5 phosphorylation. We assessed proliferation and memory differentiation of transduced T cells cultured in MSA-hoIL2 or MSA-hIL2 for one week or after repetitive tumor challenge using an HLA*0201+ NY-ESO-1+ melanoma tumor cell line (M407-nRFP) in the presence of MSA-hoIL2 or MSA-hIL2. After four tumor challenges, T cells were restimulated to quantify intracellular cytokine production. Comparisons between ho2R and ho9R T cells were made using unpaired t-tests or 2-way ANOVA. Results: Consistent with the mouse system, human T cells signaling through ho9R activated pSTAT-1, -3 and -5, whereas ho2R signaling primarily activated pSTAT5. Similar to the mouse system, ho9R signaling resulted in weaker proliferation than ho2R or wildtype IL-2 signaling (p Conclusion: In tumor-specific T cells ho9R signaling activates STAT-1, -3, and -5, promotes stemness, and maintains effector polyfunctionality despite repetitive antigen stimulation, providing human evidence for its potential in adoptive T cell therapy of cancer. Citation Format: Mito Tariveranmoshabad, Leon L. Su, Amy L. Sun, Lora K. Picton, Antoni Ribas, K. Christopher Garcia, Anusha Kalbasi. Human chimeric orthogonal IL9 receptor signaling promotes stemness and polyfunctionality for adoptive T cell therapy of cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3605.

Noroviruses are a leading cause of gastrointestinal infection in humans and mice. Understanding human norovirus (HuNoV) cell tropism has important implications for our understanding of viral pathogenesis. Murine norovirus (MNoV) is extensively used as a surrogate model for HuNoV. We previously identified CD300lf as the receptor for MNoV. Here, we generated a Cd300lf conditional knockout (CD300lfF/F) mouse to elucidate the cell tropism of persistent and non-persistent strains of murine norovirus. Using this mouse model, we demonstrate that CD300lf expression on intestinal epithelial cells (IECs), and on tuft cells in particular, is essential for transmission of the persistent MNoV strain CR6 (MNoVCR6) in vivo. In contrast, the nonpersistent MNoV strain CW3 (MNoVCW3) does not require CD300lf expression on IECs for infection. However, deletion of CD300lf in myelomonocytic cells (LysM Cre+) partially reduces CW3 viral load in lymphoid and intestinal tissues. Disruption of CD300lf expression on B cells (CD19 Cre), neutrophils (Mrp8 Cre), and dendritic cells (CD11c Cre) did not affect CW3 viral RNA levels. Finally, we show that the transcription factor STAT1, which is critical for the innate immune response, partially restricts the cell tropism of MNoVCW3 to LysM+ cells. Taken together, these data demonstrate that CD300lf expression on tuft cells is essential for MNoVCR6, that myelomonocytic cells are a major, but not exclusive, target cell of MNoVCW3, and that STAT1 signaling restricts the cellular tropism of MNoVCW3. This provides the first genetic system to study the cell type-specific role of CD300lf in norovirus pathogenesis.IMPORTANCEHuman noroviruses (HuNoVs) are a leading cause of gastroenteritis resulting in up to 200,000 deaths each year. The receptor and cell tropism of HuNoV in immunocompetent humans are unclear. We use murine norovirus (MNoV) as a model for HuNoV. We recently identified CD300lf as the sole physiologic receptor for MNoV. Here, we leverage this finding to generate a Cd300lf conditional knockout mouse to decipher the contributions of specific cell types to MNoV infection. We demonstrate that persistent MNoVCR6 requires CD300lf expression on tuft cells. In contrast, multiple CD300lf+ cell types, dominated by myelomonocytic cells, are sufficient for non-persistent MNoVCW3 infection. CD300lf expression on epithelial cells, B cells, neutrophils, and dendritic cells is not critical for MNoVCW3 infection. Mortality associated with MNoVCW3 strain in Stat1-/- mice does not require CD300lf expression on LysM+ cells, highlighting that both CD300lf receptor expression and innate immunity regulate MNoV cell tropism in vivo.

Our health care landscape is rapidly changing. With the aging population and seemingly increasing outbreak of communicable diseases, it is expected that there will be a continued demand for inpatient/critical care providers. The current COVID-19 pandemic provides a glimpse of a health care system in severe provider shortage. Adult-gerontology acute nurse practitioners (GACNPs) can play a vital part in relieving that shortage. But with the increased role, there is an increased responsibility and need for expansion of AGACNP skill set. This includes the training and utilization of point-of-care ultrasound (POCUS). The case reports and data available from countries that have already combated COVID-19 outbreak show POCUS can play a key part in managing critically ill patients on isolation precautions. This article provides my perspective on POCUS training and competency achievement for AGACNPPs.

A basic understanding of arthropod identification and their life cycles are fundamentally important for medical and health professionals because of the proven potential for these invertebrates to negatively affect the health and well-being of humans by nuisance, direct physical attack and associated distress, adverse allergic reactions, and as vectors or hosts of pathogenic organisms. Most major classes of human pathogens (viruses, bacteria, protozoa, and helminths) have evolved as agents that are capable of being transmitted by blood-feeding arthropods. These vectors act to bridge barriers that would otherwise prevent transmission by direct contact among humans or between animals and humans. A basic understanding of the epidemiology of vector-borne diseases must include knowledge of the complex life cycles of arthropods and the causative agents of their diseases. This knowledge is also essential in preventing, recognizing, treating, and controlling these potentially epidemic vector-borne diseases. Arthropods and arthropod-borne diseases continue to be difficult to control because of arthropods’ innate adaptive abilities (i.e., pesticide resistance and ability to thrive in changing environments) and their ability to disseminate new and emerging pathogens such as Zika and Mayaro viruses. This chapter discusses and examines the common features of arthropods of public health importance to include life cycles, habitats, morphology, and patterns of activity.

Author(s): Emani, S; Liu, C; Ashuri, M; Sahni, K; Wu, J; Yang, W; Nemeth, K; Shaw, LL | Abstract: Li3BN2 is investigated for the first time as a transition metal free, high capacity cathode material for Li-ion batteries. It is shown that α-Li3BN2 can exhibit a specific capacity of 890 mA h g−1 with the charge storage mechanism associated with the valence state change of N ions in the BN2 anion. The specific capacity demonstrated in this study is the highest one ever reported in literature for an intercalation-type cathode material. Further, using the valence state change of N ions as a charge storage mechanism opens the door for designing additional high performance, transition metal free electrodes in the future.

Li3BN2 is a known lithium ion conductor and has been predicted lately to be a high capacity cathode for Li-ion batteries (Nemeth, 2014) [4]. In this study, we have investigated the synthesis of Li3BN2 through reactions between Li3N and h-BN powders. Effects of the reaction temperature, holding time and reaction atmosphere on the formation of Li3BN2 have been evaluated. Rietveld refinement of X-ray diffraction patterns of all powders has been performed to quantify the percentage of each phase. The results show that both the reaction temperature and holding time affect strongly the percentage of Li3BN2 in the reaction product. Furthermore, a trace amount of oxygen in the reaction atmosphere can negatively impact the purity of the reaction product because of the high affinity of Li3BN2 towards oxidation.

The feasibility of layer-by-layer manufacturing through high-aspect-ratio (HAR) nozzles for microextrusion of paste to deposit planes has been investigated. Various conditions for paste extrusion, including nozzle moving speed, piston speed, extrusion rate, and distance between the nozzle tip and substrate, have been evaluated. By linking various microextrusion parameters together with the aid of a critical distance concept derived from microextrusion using circular nozzles and addressing the extrusion delay in response to the change of the piston speed and air pocket problems properly, we successfully microextruded single planes, multilayer objects, and larger planes made of multiple smaller planes side by side through HAR nozzles. It is further demonstrated that the X–Y dimensions of an extruded plane in the steady-state extrusion stage are determined by the nozzle travel distance and the length of the HAR nozzle opening if microextrusion is conducted with proper conditions. However, the height of the extruded plane is not only determined by the microextrusion conditions, but also affected by the drying shrinkage of the paste after microextrusion. This demonstration of the feasibility of using a HAR nozzle machine opens the door to manufacture of multimaterial, multilayer devices with high productivity in the near future.

Utilizing silicon as an anode material for Li-ion batteries has been the subject of many studies. However, due to the huge volume change of silicon during lithiation, the electrochemical performance of silicon is poor. Here, we have investigated a novel yet simple approach to synthesize nanostructured silicon/graphite composites with a carbon coating and engineered voids. High-energy ball mill is employed to convert micrometer-sized silicon and graphite to nanostructured silicon/graphite composite building blocks, while a thin carbon coating is applied to encapsulate these composite agglomerates, followed by partial etching of silicon to create engineered voids inside the composite agglomerates. The batteries made with this tailored nanostructure exhibit improved electrochemical performance over the counterparts made with silicon nanoparticles and exhibited a specific capacity of ∼1800 mA h g−1 discharge capacity at the first cycle, 580 mA h g−1 after 40 cycles, and 350 mA h g−1 after 300 cycles. This study has established a novel method scalable at industry environment and capable of producing low cost Si anodes and clearly shown that the cycle stability of the tailored nanostructure improves with increasing engineered voids in the range we have investigated.