The pharmaceutical industry is developing increasing numbers of drugs and diagnostics based on nanoparticles, and evaluating the immune response to these diverse formulations has become a challenge for scientists and regulatory agencies alike. An international panel of scientists and representatives from various agencies and companies reviewed the imitations of current tests at a workshop held at the National Cancer Institute in Frederick, Maryland. This article outlines practical strategies for identifying and controlling interferences in common evaluation methods and the implications for regulation.

Regimes of high-confinement mode have been studied in the Alcator C-Mod tokamak [Hutchinson et al., Phys. Plasmas 1, 1511 (1994)]. Plasmas with no edge localized modes (ELM-free) have been compared in detail to a new regime, enhanced Dα (EDA). EDA discharges have only slightly lower energy confinement than comparable ELM-free ones, but show markedly reduced impurity confinement. Thus EDA discharges do not accumulate impurities and typically have a lower fraction of radiated power. The edge gradients in EDA seem to be relaxed by a continuous process rather than an intermittent one as is the case for standard ELMy discharges and thus do not present the first wall with large periodic heat loads. This process is probably related to fluctuations seen in the plasma edge. EDA plasmas are more likely at low plasma current (q>3.7), for moderate plasma shaping, (triangularity ∼0.35–0.55), and for high neutral pressures. As observed in soft x-ray emission, the pedestal width is found to scale with the same parameters that determine the EDA/ELM-free boundary.

The present study was undertaken to characterize myocardial lesions in the rat induced by low doses of isoproterenol (Iso) and to correlate lesion severity with release of cardiac troponin T (cTnT) and changes in myocyte iNOS expression. Two types of cardiac injury patterns were observed. A Type I response, noted 3 or 6 hours postdosing with 8, 16, 32, or 64 mug/kg Iso, included potential reversible myocardial alterations associated with slight increases in serum cTnT (< 0.3 ng/mL) and a slight reduction in myocyte cTnT immunoreactivity. The second type of response noted 3, 6, 12, 24 or 48 hours postdosing with 125, 250, or 500 mug/kg Iso consisted of irreversible myocyte alterations, together with significant increases in serum cTnT (3-14 ng/mL) and a marked reduction of cTnT immunoreactivity. By 48 hours the hearts of rats dosed with 125-500 mug/kg Iso had developed interstitial fibrosis, and serum cTnT had declined to near control levels (0.06-0.18 ng/mL). Increases in iNOS immunoreactivity correlated with the lesion severity. These findings suggest that low doses of Iso exert complex effects on the myocardium and that the generation of NO through increased expression of iNOS could be an important factor in the pathogenesis of myocyte injury.

The use of fluorescence as an analytical technique has been growing over the last 20 years. A major factor in inhibiting more rapid growth has been the inability to make comparable fluorescence intensity measurements across laboratories. NIST recognizes the need to develop and provide primary fluorescence intensity standard (FIS) reference materials to the scientific and technical communities involved in these assays. The critical component of the effort will be the cooperation between the Federal laboratories, the manufacturers, and the technical personnel who will use the fluorescence intensity standards. We realize that the development and use of FIS will have to overcome many difficulties. However, as we outline in this article, the development of FIS is feasible.