Higher-Order Corrections to Instantons

The energy levels of the double-well potential receive, beyond perturbation theory, contributions which are non-analytic in the coupling strength; these are related to instanton effects. For example, the separation between the energies of odd- and even-parity states is given at leading order by the one-instanton contribution. However to determine the energies more accurately multi-instanton configurations have also to be taken into account. We investigate here the two-instanton contributions. First we calculate analytically higher-order corrections to multi-instanton effects. We then verify that the difference betweeen numerically determined energy eigenvalues, and the generalized Borel sum of the perturbation series can be described to very high accuracy by two-instanton contributions. We also calculate higher-order corrections to the leading factorial growth of the perturbative coefficients and show that these are consistent with analytic results for the two-instanton effect and with exact data for the first 200 perturbative coefficients.Comment: 7 pages, LaTe

Does lowering a fever >101F in children improve clinical outcomes?

Treating fever significantly increases comfort, activity, feeding, and fluid intake and decreases the patient's temperature compared with placebo (strength of recommendation (SOR): A, multiple randomized controlled trials [RCTs]). It doesn't shorten or prolong the overall duration of illness or reduce the recurrence of febrile seizures (SOR: A, multiple RCTs). In patients with varicella, reducing fever prolongs the time it takes for lesions to crust, but doesn't appear to cause group A streptococcal necrotizing fasciitis (SOR: B, multiple prospective cohorts)

Defining Breadth of Hepatitis C Virus Neutralization

Extraordinary genetic diversity is a hallmark of hepatitis C virus (HCV). Therefore, accurate measurement of the breadth of antibody neutralizing activity across diverse HCV isolates is key to defining correlates of immune protection against the virus, and essential to guide vaccine development. Panels of HCV pseudoparticle (HCVpp) or replication-competent cell culture viruses (HCVcc) can be used to measure neutralizing breadth of antibodies. These in vitro assays have been used to define neutralizing breadth of antibodies in serum, to characterize broadly neutralizing monoclonal antibodies, and to identify mechanisms of HCV resistance to antibody neutralization. Recently, larger and more diverse panels of both HCVpp and HCVcc have been described that better represent the diversity of circulating HCV strains, but further work is needed to expand and standardize these neutralization panels

Carbon Cornhole

The purpose of this design project is to create a durable lightweight yard game for players of all skill levels. Carbon Cornhole is a composite improvement on the already popular yard game, cornhole, with a new twist. The final product is based on valued feedback from customers. The board is manufactured of carbon fiber/epoxy sandwich panels with a closed cell foam core. The composite design provides a lightweight product. The panels are specifically manufactured to retain their mechanical properties when exposed to outdoor elements such as water and UV radiation. The addition of inlayed LED lights and two new skill holes allows for a new playing experience and the ability to play at night. The addition of 3D printed feet allows for the board to be played on multiple different outdoor surfaces such as grass, gravel, or concrete. Testing on the finished product will ensure the customer experiences years of enjoyment from their purchase

Self-Adjuvanting Glycopeptide Conjugate Vaccine against Disseminated Candidiasis

Our research on pathogenesis of disseminated candidiasis led to the discovery that antibodies specific for Candida albicans cell surface β-1, 2–mannotriose [β-(Man)3] protect mice. A 14 mer peptide Fba, which derived from the N-terminal portion of the C. albicans cytosolic/cell surface protein fructose-bisphosphate aldolase, was used as the glycan carrier and resulted in a novel synthetic glycopeptide vaccine β-(Man)3-Fba. By a dendritic cell-based immunization approach, this conjugate induced protective antibody responses against both the glycan and peptide parts of the vaccine. In this report, we modified the β-(Man)3-Fba conjugate by coupling it to tetanus toxoid (TT) in order to improve immunogenicity and allow for use of an adjuvant suitable for human use. By new immunization procedures entirely compatible with human use, the modified β-(Man)3-Fba-TT was administered either alone or as a mixture made with alum or monophosphoryl lipid A (MPL) adjuvants and given to mice by a subcutaneous (s.c.) route. Mice vaccinated with or, surprisingly, without adjuvant responded well by making robust antibody responses. The immunized groups showed a high degree of protection against a lethal challenge with C. albicans as evidenced by increased survival times and reduced kidney fungal burden as compared to control groups that received only adjuvant or DPBS buffer prior to challenge. To confirm that induced antibodies were protective, sera from mice immunized against the β-(Man)3-Fba-TT conjugate transferred protection against disseminated candidiasis to naïve mice, whereas C. albicans-absorbed immune sera did not. Similar antibody responses and protection induced by the β-(Man)3-Fba-TT vaccine was observed in inbred BALB/c and outbred Swiss Webster mice. We conclude that addition of TT to the glycopeptide conjugate results in a self-adjuvanting vaccine that promotes robust antibody responses without the need for additional adjuvant, which is novel and represents a major step forward in vaccine design against disseminated candidiasis

HCV Broadly Neutralizing Antibodies Use a CDRH3 Disulfide Motif to Recognize an E2 Glycoprotein Site that Can Be Targeted for Vaccine Design

Hepatitis C virus (HCV) vaccine efforts are hampered by the extensive genetic diversity of HCV envelope glycoproteins E1 and E2. Structures of broadly neutralizing antibodies (bNAbs) (e.g., HEPC3, HEPC74) isolated from individuals who spontaneously cleared HCV infection facilitate immunogen design to elicit antibodies against multiple HCV variants. However, challenges in expressing HCV glycoproteins previously limited bNAb-HCV structures to complexes with truncated E2 cores. Here we describe crystal structures of full-length E2 ectodomain complexes with HEPC3 and HEPC74, revealing lock-and-key antibody-antigen interactions, E2 regions (including a target of immunogen design) that were truncated or disordered in E2 cores, and an antibody CDRH3 disulfide motif that exhibits common interactions with a conserved epitope despite different bNAb-E2 binding orientations. The structures display unusual features relevant to common genetic signatures of HCV bNAbs and demonstrate extraordinary plasticity in antibody-antigen interactions. In addition, E2 variants that bind HEPC3/HEPC74-like germline precursors may represent candidate vaccine immunogens