Fully nonlinear extensions of Boussinesq equations are derived to simulate surface wave propagation in coastal regions. By using the velocity at a certain depth as a dependent variable (Nwogu 1993), the resulting equations have significantly improved linear dispersion properties in intermediate water depths when compared to standard Boussinesq approximations. Since no assumption of small nonlinearity is made, the equations can be applied to simulate strong wave interactions prior to wave breaking. A high-order numerical model based on the equations is developed and applied to the study of two canonical problems: solitary wave shoaling on slopes and undular bore propagation over a horizontal bed. Results of the Boussinesq model with and without strong nonlinearity are compared in detail to those of a boundary element solution of the fully nonlinear potential flow problem developed by Grilli et al. (1989). The fully nonlinear variant of the Boussinesq model is found to predict wave heights, phase speeds and particle kinematics more accurately than the standard approximation.

Cell-mediated, but not antibody-mediated, immune responses protect humans against certain pathogens that produce chronic diseases such as leishmaniasis. Effective vaccination against such pathogens must therefore produce an immunological "imprint" so that stable, cell-mediated immunity is induced in all individuals after natural infection. BALB/c mice "innately susceptible" to Leishmania major produce antibodies after substantial infection. In the present study, "susceptible" mice injected with a small number of parasites mounted a cell-mediated response and acquired resistance to a larger, normally pathogenic, challenge. This vaccination strategy may be applicable in diseases in which protection is dependent on cell-mediated immunity.

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A Boussinesq-type model is derived which is accurate to O(kh)4 and which retains the full representation of the fluid kinematics in nonlinear surface boundary condition terms, by not assuming weak nonlinearity. The model is derived for a horizontal bottom, and is based explicitly on a fourth-order polynomial representation of the vertical dependence of the velocity potential. In order to achieve a (4,4) Padé representation of the dispersion relationship, a new dependent variable is defined as a weighted average of the velocity potential at two distinct water depths. The representation of internal kinematics is greatly improved over existing O(kh)2 approximations, especially in the intermediate to deep water range. The model equations are first examined for their ability to represent weakly nonlinear wave evolution in intermediate depth. Using a Stokes-like expansion in powers of wave amplitude over water depth, we examine the bound second harmonics in a random sea as well as nonlinear dispersion and stability effects in the nonlinear Schrödinger equation for a narrow-banded sea state. We then examine numerical properties of solitary wave solutions in shallow water, and compare model performance to the full solution of Tanaka (1986) as well as the level 1, 2 and 3 solutions of Shields & Webster (1988).

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Infection of susceptible BALB/c mice with a large, moderate, or low number of Leishmania major parasites respectively results in progressive disease, the formation of substantial but stable lesions, denoted as borderline disease, and the absence of a visible lesion. Infection with a low number of parasites results over the long term in either subclinical infections or an asymptomatic state. Subclinical mice produce a predominant Th1 response and are resistant to challenge, in contrast to their asymptomatic counterparts. Statistical and other evidence suggest that the asymptomatic state can arise from a subclinical state following parasite clearance, with consequent loss of resistance. Cell transfer studies demonstrate unequivocally that immune cells from subclinical mice can protect naive mice against a pathogenic challenge and can clear the parasite, leaving the mice susceptible to a rechallenge infection. This susceptibility is associated with the disappearance of both parasite-specific effector and memory T cells from secondary lymphoid organs. These findings have implications for vaccination, maintenance of memory, and prevention of reactivation disease.

Background and Aims The presence of gastrointestinal symptoms and high levels of viral RNA in the stool suggest active Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) replication within enterocytes. Methods Here, in multiple, large cohorts of patients with inflammatory bowel disease (IBD), we have studied the intersections between Coronavirus Disease 2019 (COVID-19), intestinal inflammation and IBD treatment. Results A striking expression of ACE2 on the small bowel enterocyte brush border supports intestinal infectivity by SARS-CoV-2. Commonly used IBD medications, both biologic and non-biologic, do not significantly impact ACE2 and TMPRSS2 receptor expression in the uninflamed intestines. Additionally, we have defined molecular responses to COVID-19 infection that are also enriched in IBD, pointing to shared molecular networks between COVID-19 and IBD. Conclusions These data generate a novel appreciation of the confluence of COVID-19- and IBD-associated inflammation and provide mechanistic insights supporting further investigation of specific IBD drugs in the treatment of COVID-19.

Infections of highly susceptible BALB/c mice with virulent strains of Trypanosoma congolense or Trypanosoma brucei result in rapid death (8 days). We have previously shown that this mortality is IFN-γ dependent. In this study we show that IFN-γ is produced predominantly by CD3+Thy1.2+TCRβ+CD4+ T cells shortly before the death of infected mice. Mortality may therefore be dependent on IFN-γ-producing CD4+ T cells. Surprisingly, infected CD4+/+ and CD4−/− BALB/c mice have similar parasitemia and survival time. In infected CD4−/− mice, the production of both IFN-γ and IL-10 is very low, suggesting that both cytokines are predominantly produced by CD4+ T cells and that the outcome of the disease might depend on the balance of their effects. Infected BALB/c mice partially depleted of CD4+ T cells or MHC class II function have lower parasitemia and survive significantly longer than infected normal BALB/c mice or infected BALB/c mice whose CD4+ T cells are fully depleted. Partial depletion of CD4+ T cells markedly reduces IFN-γ secretion without a major effect on the production of IL-10 and parasite-specific IgG2a Abs. Based on our previous and current data, we conclude that a subset of a pathogenic, MHC class II-restricted CD4+ T cells (Tp cells), activated during the course of T. congolense infection, mediates early mortality in infected BALB/c mice via excessive synthesis of IFN-γ. IFN-γ, in turn, exerts its pathological effect by enhancing the cytokine release syndrome of the macrophage system activated by the phagocytosis of parasites. We speculate that IL-10-producing CD4+ T cells might counteract this effect.