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One cannot legitimately discuss American anti-war novels without the inclusion of John Dos Passos's Three Soldiers (1921). Set in WWI, the novel entered a market hungry for tales of the [...]

The introduction of Rituximab has greatly improved therapeutic options for patients with B-cell non-Hodgkin lymphoma (B-NHL). However, a substantial fraction of patients with aggressive B-NHL fails first-line therapy, and most patients with relapsing indolent B-NHL eventually acquire Rituximab resistance. Molecular understanding of the underlying mechanisms facilitates the development of pharmacologic strategies to overcome resistance. Rituximab exerts its activity on CD20-expressing B-cells by indirect and direct effector mechanisms. Indirect mechanisms are complement-dependent cytotoxicity (CDC), and antibody-dependent cell-mediated cytotoxicity (ADCC). Direct activities, such as growth inhibition, induction of apoptosis and chemosensitisation, have been reported, but are less defined. Moreover, the relative contribution of CDC, ADCC and direct mechanisms to the activity of Rituximab in vivo is unclear. Down-regulation of CD20 and expression of complement inhibitors have been described as escape mechanisms in B-NHL. Recent reports suggest that deregulated phosphoinositide-3-kinase (PI3K)/Akt, mitogen-activated kinases (MAPK) and nuclear-factor κB (NF-κB), as well as up-regulation of anti-apoptotic proteins may determine the efficacy of Rituximab to kill B-NHL cells in vitro and in vivo. The latter signalling pathways are attractive targets for pharmacologic modulation of resistance to Rituximab. With the advent of new inhibitors and antibodies, rationally designed clinical trials addressing Rituximab resistance are feasible. [ABSTRACT FROM AUTHOR]

The room-temperature refractive index is measured for three different prior cooling rates (approximately 10, 50, and 250 K/h) for two glasses especially developed for precision molding. The empirical logarithmic relationship between the cooling rate and the refractive index is also reproduced for the comparatively high cooling rate of ca. 250 K/h. The same relationship is found in a simulation of these cooling rates by the semiempirical Tool–Narayanaswamy–Moynihan model for structural relaxation, with the necessary parameters obtained from differential scanning calorimetry and temperature jump experiments. The measured and the simulated refractive indices coincide within the limits of experimental error. The results demonstrate that the index drop, which is observed when these glasses are first cooled at a regular optical cooling rate (e.g., 2 K/h), and then precision molded (typical cooling rate 1000 K/h), can be understood considering the concepts of structural relaxation. [ABSTRACT FROM AUTHOR]