ABSTRACT
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ABSTRACT
We report on measurements of the switching current distributions on two-dimensional superconducting NbTiN strips that are 5 nm thick and 80 nm wide. We observe that the width of the switching current distributions has a non-monotonous temperature dependence, where it is constant at the lowest temperatures up to about 1.5 K, after which it increases with temperature until 2.2 K. Above 2.5 K any increase in temperature decreases the distribution width which at 4.0 K is smaller than half the width observed at 0.3 K. By using a careful analysis of the higher order moments of the switching distribution, we show that this temperature dependence is caused by switching due to multiple fluctuations. We also find that the onset of switching by multiple events causes the current dependence of the switching rate to develop a characteristic deviation from a pure exponential increase, that becomes more pronounced at higher temperatures, due to the inclusion of higher order terms.
ABSTRACT
Autoimmune diabetes is caused by selective loss of insulin-producing pancreatic beta-cells. The main factors directly implicated in beta-cell death are autoreactive, cytotoxic (islet-antigen specific) T-lymphocytes (CTL), and inflammatory cytokines. In this study, we have used an antigen-specific model of virally induced autoimmune diabetes to demonstrate that even high numbers of autoreactive CTL are unable to lyse beta-cells by perforin unless major histocompatibility complex class I is upregulated on islets. This requires the presence of inflammatory cytokines induced by viral infection of the exocrine pancreas but not of the beta-cells. Unexpectedly, we found that the resulting perforin-mediated killing of beta-cells by autoreactive CTL is not sufficient to lead to clinically overt diabetes in vivo, and it is not an absolute prerequisite for the development of insulitis, as shown by studies in perforin-deficient transgenic mice. In turn, destruction of beta-cells also requires a direct effect of gamma-interferon (IFN-gamma), which is likely to be in synergy with other cytokines, as shown in double transgenic mice that express a mutated IFN-gamma receptor on their beta-cells in addition to the viral (target) antigen and do not develop diabetes. Thus, destruction of most beta-cells occurs as cytokine-mediated death and requires IFN-gama in addition to perforin. Understanding these kinetics could be of high conceptual importance for the design of suitable interventions in prediabetic individuals at risk to develop type 1 diabetes.
