Bear Minimum: Ultralight Composite Bear Canister

The ultralight backpacking community needs a strong, easy to use, safe bear canister that is lighter than current market products for trekking in the backcountry. A full design of the lid for the bear canister is to be completed. This includes the locking mechanism to ensure it is bear proof, the interface between the lid and the canister, and the structure of the lid so it passes the strength and weight specifications. The lid, along with the already designed canister body, is to be manufactured with formal documentation. The lid will initially be tested separately and then with the canister body as an assembly. All tests will be to either verify or reject one or more of the design specifications listed later in this document. The overarching goal of the project is to find a balance of two project requirements: making a rigid lid that is, when combined with the canister body, less than 1.3 lbf and still meeting the Interagency Grizzly Bear Committee (IGBC) certification strength requirements

Determination of T Follicular Helper Cell Fate by Dendritic Cells

T follicular helper (Tfh) cells are a specialized subset of CD4+ T cells that collaborate with B cells to promote and regulate humoral responses. Unlike other CD4+ effector lineages, Tfh cells require interactions with both dendritic cells (DCs) and B cells to complete their differentiation. While numerous studies have assessed the potential of different DC subsets to support Tfh priming, the conclusions of these studies depend heavily on the model and method of immunization used. We propose that the location of different DC subsets within the lymph node (LN) and their access to antigen determine their potency in Tfh priming. Finally, we provide a three-step model that accounts for the ability of multiple DC subsets and related lineages to support the Tfh differentiation program

Determination of T Follicular Helper Cell Fate by Dendritic Cells.

T follicular helper (Tfh) cells are a specialized subset of CD4+ T cells that collaborate with B cells to promote and regulate humoral responses. Unlike other CD4+ effector lineages, Tfh cells require interactions with both dendritic cells (DCs) and B cells to complete their differentiation. While numerous studies have assessed the potential of different DC subsets to support Tfh priming, the conclusions of these studies depend heavily on the model and method of immunization used. We propose that the location of different DC subsets within the lymph node (LN) and their access to antigen determine their potency in Tfh priming. Finally, we provide a three-step model that accounts for the ability of multiple DC subsets and related lineages to support the Tfh differentiation program

Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes.

There are currently limited Food and Drug Administration (FDA)-approved drugs and vaccines for the treatment or prevention of Coronavirus Disease 2019 (COVID-19). Enhanced understanding of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and pathogenesis is critical for the development of therapeutics. To provide insight into viral replication, cell tropism, and host-viral interactions of SARS-CoV-2, we performed single-cell (sc) RNA sequencing (RNA-seq) of experimentally infected human bronchial epithelial cells (HBECs) in air-liquid interface (ALI) cultures over a time course. This revealed novel polyadenylated viral transcripts and highlighted ciliated cells as a major target at the onset of infection, which we confirmed by electron and immunofluorescence microscopy. Over the course of infection, the cell tropism of SARS-CoV-2 expands to other epithelial cell types including basal and club cells. Infection induces cell-intrinsic expression of type I and type III interferons (IFNs) and interleukin (IL)-6 but not IL-1. This results in expression of interferon-stimulated genes (ISGs) in both infected and bystander cells. This provides a detailed characterization of genes, cell types, and cell state changes associated with SARS-CoV-2 infection in the human airway

A Tale of Two Shares: Why Two-Share Threshold Implementation Seems Worthwhile-and Why it is Not

In this work, we explore the possibilities for practical Threshold Implementation (TI) with only two shares in order for a smaller design that needs less randomness but is still first-order leakage resistant. We present the first two-share Threshold Implementations of two lightweight block ciphers---Simon and Present. The implementation results show that two-share TI gains in compactness while loses in throughput compared with three-share schemes. Moreover, the leakage analyses show that two-share TI retains perfect first-order resistance but is shadowed by a strong second-order leakage, making it less worthwhile

Atypical is the new norm, for B cells and the rest of us.

An unusual form of activated B cells in adults is described, called atypical B cells, both in the steady state and after vaccination

Structure and function of the immune system in the spleen.

The spleen is the largest secondary lymphoid organ in the body and, as such, hosts a wide range of immunologic functions alongside its roles in hematopoiesis and red blood cell clearance. The physical organization of the spleen allows it to filter blood of pathogens and abnormal cells and facilitate low-probability interactions between antigen-presenting cells (APCs) and cognate lymphocytes. APCs specific to the spleen regulate the T and B cell response to these antigenic targets in the blood. This review will focus on cell types, cell organization, and immunologic functions specific to the spleen and how these affect initiation of adaptive immunity to systemic blood-borne antigens. Potential differences in structure and function between mouse and human spleen will also be discussed

Flow cytometric identification of T fh 13 cells in mouse and human

Anaphylaxis is a life-threatening allergic reaction caused by cross-linking of high-affinity IgE antibodies on the surface of mast cells and basophils. Understanding the cellular mechanisms that lead to high-affinity IgE production is required to develop better therapeutics for preventing this severe reaction. A recently discovered population of T follicular helper Tfh13 cells regulates the production of high-affinity IgE in mouse models of allergy and can also be found in patients with allergies with IgE antibodies against food or aeroallergens. Here we describe optimized protocols for identifying Tfh13 cells in both mice and humans

Oral anaphylaxis to peanut in a mouse model is associated with gut permeability but not with Tlr4 or Dock8 mutations.

BACKGROUND: The etiology of food allergy is poorly understood; mouse models are powerful systems to discover immunologic pathways driving allergic disease. C3H/HeJ mice are a widely used model for the study of peanut allergy because, unlike C57BL/6 or BALB/c mice, they are highly susceptible to oral anaphylaxis. However, the immunologic mechanism of this strain\u27s susceptibility is not known. OBJECTIVE: We aimed to determine the mechanism underlying the unique susceptibility to anaphylaxis in C3H/HeJ mice. We tested the role of deleterious Toll-like receptor 4 (Tlr4) or dedicator of cytokinesis 8 (Dock8) mutations in this strain because both genes have been associated with food allergy. METHODS: We generated C3H/HeJ mice with corrected Dock8 or Tlr4 alleles and sensitized and challenged them with peanut. We then characterized the antibody response to sensitization, anaphylaxis response to both oral and systemic peanut challenge, gut microbiome, and biomarkers of gut permeability. RESULTS: In contrast to C3H/HeJ mice, C57BL/6 mice were resistant to anaphylaxis after oral peanut challenge; however, both strains undergo anaphylaxis with intraperitoneal challenge. Restoring Tlr4 or Dock8 function in C3H/HeJ mice did not protect from anaphylaxis. Instead, we discovered enhanced gut permeability resulting in ingested allergens in the bloodstream in C3H/HeJ mice compared to C57BL/6 mice, which correlated with an increased number of goblet cells in the small intestine. CONCLUSIONS: Our work highlights the potential importance of gut permeability in driving anaphylaxis to ingested food allergens; it also indicates that genetic loci outside of Tlr4 and Dock8 are responsible for the oral anaphylactic susceptibility of C3H/HeJ mice