Reflectionless potentials and resonant scattering of flat-top and thin-top solitons.

We identify a class of potentials for which the scattering of flat-top solitons and thin-top solitons of the nonlinear Schrödinger equation with dual nonlinearity can be reflectionless. The scattering is characterized by sharp resonances between regimes of full transmission and full quantum reflection. Perturbative expansion in terms of the magnitude of radiation losses leads to the general form of reflectionless potentials. Simulating the scattering of flat-top solitons and thin-top solitons confirms the reflectionless feature of these potentials.

Bound-states spectrum of the nonlinear Schrödinger equation with Pöschl-Teller and square-potential wells.

We obtain the spectrum of bound states for modified Pöschl-Teller and square-potential wells in the nonlinear Schrödinger equation. For a fixed norm of bound states, the spectrum for both potentials turns out to consist of a finite number of multinode localized states. Soliton scattering by these two potentials confirmed the existence of the localized states which form as trapped modes. Critical speed for quantum reflection was calculated using the energies of the trapped modes.

High-speed soliton ejection generated from the scattering of bright solitons by modulated reflectionless potential wells.

We investigate numerically and theoretically the conditions leading to soliton ejection stimulated through the scattering of bright solitons by modulated reflectionless potential wells. Such potential wells allow for the possibility of controlled ejection of solitons with significantly high speeds. At the outset, we describe the scattering setup and characterize the soliton ejection in terms of the different parameters of the system. Then, we formulate a theoretical model revealing the underlying physics of soliton ejection. The model is based on energy and norm exchange between the incident soliton and a stable trapped mode corresponding to an exact solution of the governing nonlinear Schrödinger equation. Remarkably, stationary solitons can lead to high-speed soliton ejection where part of the nonlinear interaction energy transforms to translational kinetic energy of the ejected soliton. Our investigation shows that soliton ejection always occurs whenever the incident soliton norm is greater than that of the trapped mode whereas their energy is almost the same. Once the incident soliton is trapped, the excess in norm turns to an ejected soliton in addition to a small amount of radiation that share translational kinetic energy. We found that higher ejection speeds are obtained with multinode trapped modes that have higher binding energy. Simultaneous two-soliton ejection has been also induced by two solitons scattering with the potential from both of its sides. An ejection speed almost twice as that of single soliton ejection was obtained. Ejection outcome and ejection speed turn out to be sensitive to the relative phase between the two incoming solitons, which suggests a tool for soliton phase interferometry.

Singular soliton molecules of the nonlinear Schrödinger equation.

We derive an exact solution to the local nonlinear Schrödinger equation (NLSE) using the Darboux transformation method. The solution describes the profile and dynamics of a two-soliton molecule. Using an algebraically decaying seed solution, we obtain a two-soliton solution with diverging peaks, which we denote as singular soliton molecule. We find that this solution has a finite binding energy. We calculate the force and potential of interaction between the two solitons, which turn out to be of molecular-type. The robustness of the bond between the two solitons is also verified. Furthermore, we obtain an exact solution to the nonlocal NLSE using the same method and seed solution. The solution in this case corresponds to an elastic collision of a soliton, a breather soliton on flat background, and a breather soliton on a background with linear ramp. Finally, we consider an NLSE which is nonlocal in time rather than space. Although we did not find a Lax pair to this equation, we derive three exact solutions.

Early T-cell defects in pre-type 1 diabetes.

Alterations of lymphocyte subsets have been recently reported in pre-type 1 diabetes but the relation with other immunological markers, in particular islet cell antibodies (ICA), is still unknown. In the present study, we have investigated prospectively changes of lymphocyte subsets in 86 first-degree relatives of patients affected by type 1 diabetes and correlated such modifications with ICA titres. Among individuals with persistent ICA, 8 had ICA titres of more than 20 JDF units, 14 had ICA titres between 5 and 20 JDF units and 64 had ICA titres between 0 and 5 JDF units. First-degree relatives with ICA titres of more than 20 JDF units had significantly decreased proportions of CD3 cells. This reduction was predominantly in the CD4 subset, giving rise to a decreased CD4/CD8 lymphocyte ratio. Those with ICA titres between 5 and 20 JDF units showed abnormalities in both CD3 and CD4 lymphocytes, but not in CD4/CD8 lymphocyte ratio. Further characterization of the CD4 cell subset was performed using three other monoclonal antibodies, CD45RO (UCHL1), CD45RA and CD29, phenotyping memory T-cells, the inducer cells of suppressor function and helper-inducer cells, respectively. The proportions of total CD45RO and CD45RA were not significantly different among first-degree relative with distinct ICA titres in a cross-sectional study, whereas a trend towards a reduced proportion of CD4/CD45RA cells was observed. The longitudinal study demonstrated that individuals potentially susceptible to the development of type 1 diabetes and who possess high titres of ICA have impairment of CD4/CD8 lymphocyte ratio, mainly due to a reduction in the CD4 subset.(ABSTRACT TRUNCATED AT 250 WORDS)

On the pathogenesis of type 1 (insulin-dependent) diabetes mellitus: facts, areas still under development and new perspectives.

The observations emerged from the pancreatic transplant experiments in identical twins indicate that Type I diabetic patients maintain memory cytotoxic T cells for several years and these can be "re-awakened" when Class I identical beta cells are re-introduced into the diabetic melieu. In addition, these data have shown that these lymphocytes can (in a matter of a few weeks) cause rapid irreversible decompensation of beta cell function. From this, an important lesson is learnt: cytotoxic T cells, when generated in sufficient number against beta cells do not leave much "breathing space" for these cells. This has important implications for explaining the long latency period preceding the acute onset of Type I diabetes. ICA, when produced, seem unable to cause gross damage to beta cells. They persist for several years in the blood, but beta cell function remains apparently unaltered. It is only when cytotoxic T cells, with fine specificity for beta cells are generated that the 'killing cycle' is completed. Whether these cells are present all the time, and kept under tight control by active suppressor mechanisms or whether they appear only after an environmental trigger (e.g., retroviruses) is unknown. If the former is the case, this would give strong support to the suggested important role of suppressor T cells in the pathogenetic circuit. Some evidence for this has been produced (rev. in [116]) but, obviously, it requires confirmation (see debate which followed [116]). If, on the other hand, the latter is experimentally confirmed, one can return to the theory that cytotoxic T cells acquire the characteristics of autoreactivity by expressing receptors on their surface in a configuration which enables combination with self-autoantigens (rev. in [45]). In summary, the study of the etiopathogenesis of Type I diabetes and human autoimmunity in general has attracted a great deal of interest among immunologists. It is only by further dissecting the various limbs of the undesirable immune response against beta cells and, by trying to formulate novel hypotheses, sometimes against accepted dogmas [32], that the complete picture will be finally disclosed. At this stage it will be possible to design effective therapy trials, so that Type I diabetes and other related autoimmune disorders ultimately may be prevented.

Persistent reduction of CD4/CD8 lymphocyte ratio and cell activation before the onset of type 1 (insulin-dependent) diabetes.

Over a period of 5 years, lymphocyte subpopulations and their markers of activation were studied prospectively in 56 first degree relatives of Type 1 (insulin-dependent) diabetic probands. Lymphocytes were phenotyped using a panel of monoclonal antibodies which recognise CD3, CD4, CD8 lymphocytes, K/NK cells, HLA Class II products and IL-2 receptors (IL-2r). Twenty-six subjects were negative for islet cell antibody (ICA), 18 had complement fixing ICA (CF-ICA) and 12 only conventional ICA (ICA-IgG). The total number of observations (blood samples collected) was 386. Overall, changes in T cell data were observed in the three groups of first degree relatives compared to 70 normal subjects without a family history of diabetes. Six individuals developed Type 1 diabetes in the course of the study. They all possessed CF-ICA and five out of six showed a persistent reduction (less than 1.5) of the CD4/CD8 lymphocyte ratio before the clinical onset of the disease. Activated lymphocytes were found on two occasions in two of these subjects. We conclude that imbalance of lymphocyte immunoregulatory subsets is present before the onset of Type 1 diabetes in susceptible individuals; the persistence of a reduced CD4/CD8 lymphocyte ratio may reflect the ongoing process leading to B-cell destruction.

A cell surface monoclonal antibody (H366) helps to discriminate human cytotoxic from suppressor T cells.

A study has been undertaken to differentiate T cytotoxic (Tc) and T suppressor (Ts) cell subsets using a monoclonal antibody termed H366 (mouse IgG2b) previously reported to phenotype natural killer and killer (NK/K) cells. Mononuclear cell suspensions from 14 normal subjects were depleted of H366+ cells by means of complement dependent cytotoxicity and the remaining cells were phenotyped with CD8 and CD4 monoclonal antibodies. The effects of depletion with H366 plus complement (C1) on the induction and activity of suppressor and cytotoxic T cells was also examined. The results indicate that H366 antibody recognizes in addition to NK/K cells, a population of Tc but not Ts or helper cells. Therefore, H366 antibody can be useful for obtaining Ts enriched lymphocyte subpopulations and this property may also be used for the enumeration of suppressor cells in the peripheral blood in disease states.

Prospective study of lymphocyte subsets in subjects genetically susceptible to type 1 (insulin-dependent) diabetes.

A prospective study of lymphocyte subsets has been carried out for 18 months in 58 healthy first-degree relatives of Type 1 (insulin-dependent) probands. Subjects selected for presence or absence of islet cell antibodies included 10 with complement-fixing islet cell antibodies, 10 with conventional islet cell antibodies and 38 without islet cell antibodies. Immunoregulatory and effector lymphocytes subsets, and in particular activated T-cells, were investigated using a panel of monoclonal antibodies. The results showed no significant changes in total T, helper, suppressor/cytotoxic cell or K/NK cells. Activated T-cells were observed at least once in 22 subjects using the 4F2 monoclonal antibody and in 11 using the Tac antibody. Seven subjects had 4F2-positive cells on repeated occasions and one twice showed Tac-positive cells. Fluctuations and/or loss of islet cell antibodies were observed during follow-up. There was no correlation between presence of activated T-cells and either islet cell antibody status of HLA haplotype sharing with the diabetic proband. On the other hand, a significant correlation was observed between HLA-DR3 positivity of subjects and the occurrence of activated T-cells (both 4F2-positive and Tac-positive). We conclude that subjects with HLA-DR3 may be especially prone to T-cell activation. As none of the 'high risk' individuals developed diabetes in the course of follow-up, the relevance of these observations in the pathogenesis of Type 1 diabetes needs more prolonged investigation.

Rabbit anti-EL4 serum. A reagent which discriminates between murine cytotoxic and suppressor cells.

Antisera against the C57B1 (H-2b) mouse lymphoma, EL4, were prepared in rabbits. After absorption with mouse liver, red cells and thymocytes, the antisera appeared to be cytotoxic for a subpopulation of peripheral T cells. The absorbed antisera blocked the immunosuppressive function observed when spleen cells from mice undergoing a graft versus host reaction were added to cells responding in vitro to sheep erythrocytes. This antiserum was unreactive against the cytotoxic cells also induced in this system. These results substantiate our previous finding that these antisera are specific for T-suppressor as opposed to T-helper or cytotoxic lymphocyte subpopulations.

Rabbit anti-EL4 serum. A reagent with specificity for a population of murine suppressor cells.

Antisera against the C57B1 (H-2b) mouse lymphoma, EL4 were prepared in rabbits. After absorption with mouse liver, red cells and thymocytes the antisera appeared to be cytotoxic for a subpopulation of peripheral T cells. The absorbed antisera blocked the immunosuppressor function of Con A-stimulated splenic lymphocytes, but was unreactive against Con A-stimulated and allogeneically primed cytotoxic cells, or helper T cells. Consequently, heteroantiserum against EL4 may provide a useful reagent for the differentiation of cytotoxic from suppressor T-cell subsets.