Identification and immune assessment of T cell epitopes in five Plasmodium falciparum blood stage antigens to facilitate vaccine candidate selection and optimization

The hurdles to effective blood stage malaria vaccine design include immune evasion tactics used by the parasite such as redundant invasion pathways and antigen variation among circulating parasite strains. While blood stage malaria vaccine development primarily focuses on eliciting optimal humoral responses capable of blocking erythrocyte invasion, clinically-tested Plasmodium falciparum (Pf) vaccines have not elicited sterile protection, in part due to the dramatically high levels of antibody needed. Recent development efforts with non-redundant, conserved blood stage antigens suggest both high antibody titer and rapid antibody binding kinetics are important efficacy factors. Based on the central role of helper CD4 T cells in development of strong, protective immune responses, we systematically analyzed the class II epitope content in five leading Pf blood stage antigens (RH5, CyRPA, RIPR, AMA1 and EBA175) using in silico, in vitro, and ex vivo methodologies. We employed in silico T cell epitope analysis to enable identification of 67 HLA-restricted class II epitope clusters predicted to bind a panel of nine HLA-DRB1 alleles. We assessed a subset of these for HLA-DRB1 allele binding in vitro, to verify the in silico predictions. All clusters assessed (40 clusters represented by 46 peptides) bound at least two HLA-DR alleles in vitro. The overall epitope prediction to in vitro HLA-DRB1 allele binding accuracy was 71%. Utilizing the set of RH5 class II epitope clusters (10 clusters represented by 12 peptides), we assessed stimulation of T cells collected from HLA-matched RH5 vaccinees using an IFN-γ T cell recall assay. All clusters demonstrated positive recall responses, with the highest responses – by percentage of responders and response magnitude – associated with clusters located in the N-terminal region of RH5. Finally, a statistically significant correlation between in silico epitope predictions and ex vivo IFN-γ recall response was found when accounting for HLA-DR matches between the epitope predictions and donor HLA phenotypes. This is the first comprehensive analysis of class II epitope content in RH5, CyRPA, RIPR, AMA1 and EBA175 accompanied by in vitro HLA binding validation for all five proteins and ex vivo T cell response confirmation for RH5

Giant Superfluorescent Bursts from a Semiconductor Magnetoplasma

Currently, considerable resurgent interest exists in the concept of superradiance (SR), i.e., accelerated relaxation of excited dipoles due to cooperative spontaneous emission, first proposed by Dicke in 1954. Recent authors have discussed SR in diverse contexts, including cavity quantum electrodynamics, quantum phase transitions, and plasmonics. At the heart of these various experiments lies the coherent coupling of constituent particles to each other via their radiation field that cooperatively governs the dynamics of the whole system. In the most exciting form of SR, called superfluorescence (SF), macroscopic coherence spontaneously builds up out of an initially incoherent ensemble of excited dipoles and then decays abruptly. Here, we demonstrate the emergence of this photon-mediated, cooperative, many-body state in a very unlikely system: an ultradense electron-hole plasma in a semiconductor. We observe intense, delayed pulses, or bursts, of coherent radiation from highly photo-excited semiconductor quantum wells with a concomitant sudden decrease in population from total inversion to zero. Unlike previously reported SF in atomic and molecular systems that occur on nanosecond time scales, these intense SF bursts have picosecond pulse-widths and are delayed in time by tens of picoseconds with respect to the excitation pulse. They appear only at sufficiently high excitation powers and magnetic fields and sufficiently low temperatures - where various interactions causing decoherence are suppressed. We present theoretical simulations based on the relaxation and recombination dynamics of ultrahigh-density electron-hole pairs in a quantizing magnetic field, which successfully capture the salient features of the experimental observations.Comment: 21 pages, 4 figure

Business school learning goals: Alignment with evidence-based models and accreditation standards

Programmatic learning goals serve as the foundation for an educational institution’s curriculum design and assurance of learning processes. The purpose of our study is to determine the relevance or alignment of undergraduate business school learning goals. We identify the learning goals of US undergraduate business programs accredited by the Association to Advance Collegiate Schools of Business-International (AACSB) and determine the extent to which the goals are aligned with (a) evidence-based competencies that are needed for managerial success (including the ‘Great Eight’ and the ‘hyperdimensional taxonomy’) and (b) content areas identified in AACSB’s Eligibility Procedures and Accreditation Standards for Business Accreditation. We found that learning goals conform to AACSB Standards and evidence-based managerial competencies, but goals are most closely aligned with AACSB Standards, followed by the Great Eight, and the hyperdimensional taxonomy, respectively. We discuss the implications of our findings with respect to business schools’ assurance of learning processes and provide recommendations for AACSB, business schools, the broader academy, and future research

Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature

Interactions between the host and gut microbial community likely contribute to Crohn disease (CD) pathogenesis; however, direct evidence for these interactions at the onset of disease is lacking. Here, we characterized the global pattern of ileal gene expression and the ileal microbial community in 359 treatment-naive pediatric patients with CD, patients with ulcerative colitis (UC), and control individuals. We identified core gene expression profiles and microbial communities in the affected CD ilea that are preserved in the unaffected ilea of patients with colon-only CD but not present in those with UC or control individuals; therefore, this signature is specific to CD and independent of clinical inflammation. An abnormal increase of antimicrobial dual oxidase (DUOX2) expression was detected in association with an expansion of Proteobacteria in both UC and CD, while expression of lipoprotein APOA1 gene was downregulated and associated with CD-specific alterations in Firmicutes. The increased DUOX2 and decreased APOA1 gene expression signature favored oxidative stress and Th1 polarization and was maximally altered in patients with more severe mucosal injury. A regression model that included APOA1 gene expression and microbial abundance more accurately predicted month 6 steroid-free remission than a model using clinical factors alone. These CD-specific host and microbe profiles identify the ileum as the primary inductive site for all forms of CD and may direct prognostic and therapeutic approaches