Pyrazolopyrimidines: Potent Inhibitors Targeting the Capsid of Rhino‐ and Enteroviruses

There are currently no drugs available for the treatment of enterovirus (EV)‐induced acute and chronic diseases such as the common cold, meningitis, encephalitis, pneumonia, and myocarditis with or without consecutive dilated cardiomyopathy. Here, we report the discovery and characterization of pyrazolopyrimidines, a well‐tolerated and potent class of novel EV inhibitors. The compounds inhibit the replication of a broad spectrum of EV in vitro with IC₅₀ values between 0.04 and 0.64 μM for viruses resistant to pleconaril, a known capsid‐binding inhibitor, without affecting cytochrome P450 enzyme activity. Using virological and genetics methods, the viral capsid was identified as the target of the most promising, orally bioavailable compound 3‐(4‐trifluoromethylphenyl)amino‐6‐phenylpyrazolo[3,4‐d]pyrimidine‐4‐amine (OBR‐5‐340). Its prophylactic as well as therapeutic application was proved for coxsackievirus B3‐induced chronic myocarditis in mice. The favorable pharmacokinetic, toxicological, and pharmacodynamics profile in mice renders OBR‐5‐340 a highly promising drug candidate, and the regulatory nonclinical program is ongoing.     

A Review and perspective on surveillance of Bernoulli processes

Bernoulli processes have been monitored using a wide variety of techniques in statistical process control. The data consist of information on successive items classified as conforming (nondefective) or nonconforming (defective). In some cases, the probability of obtaining a nonconforming item is very small; this is known as a high quality process. This area of statistical process control is also applied to health‐related monitoring, where the incidence rate of a medical problem such as a congenital malformation is of interest. In these applications, standard Shewhart control charts based on the binomial distribution are no longer useful. In our expository paper, we review the methods implemented for these scenarios and present ideas for future work in this area. We offer advice to practitioners and present a comprehensive literature review for researchers. Copyright © 2011 John Wiley & Sons, Ltd.     

Perceived past, present, and future control and adjustment to stressful life events.

[Correction Notice: An erratum for this article was reported in Vol 100(4) of Journal of Personality and Social Psychology (see record 2011-05716-005). There is an error on page 758. In the sentence “Present control predicted later event-specific distress in Sample 1( β = .17, p