Study of the biological activity of novel synthetic compounds with antiviral properties against human rhinoviruses

Picornaviridae represent a very large family of small RNA viruses, some of which are the cause of important human and animal diseases. Since no specific therapy against any of these viruses currently exists, palliative symptomatic treatments are employed. The early steps of the picornavirus replicative cycle seem to be privileged targets for some antiviral compounds like disoxaril and pirodavir. Pirodavir's main weakness is its cytotoxicity on cell cultures at relatively low doses. In this work some original synthetic compounds were tested, in order to find less toxic compounds with an improved protection index (PI) on infected cells. Using an amino group to substitute the oxygen atom in the central chain, such as that in the control molecule pirodavir, resulted in decreased activity against Rhinoviruses and Polioviruses. The presence of an -ethoxy-propoxy- group in the central chain (as in compound I-6602) resulted in decreased cell toxicity and in improved anti-Rhinovirus activity. This compound actually showed a PI >700 on HRV14, while pirodavir had a PI of 250. These results demonstrate that modification of pirodavir's central hydrocarbon chain can lead to the production of novel derivatives with low cytotoxicity and improved PI against some strains of Rhinoviruses.     

A nonparametric lack-of-fit test for heteroscedastic regression models

A simple test is proposed for examining the correctness of a given completely specified response function against unspecified general alternatives in the context of univariate regression. The usual diagnostic tools based on residual plots are useful but heuristic. We introduce a formal statistical test supplementing the graphical analysis. Technically, the test statistic is the maximum length of the sequences of ordered (with respect to the covariate) observations that are consecutively overestimated or underestimated by the candidate regression function. Note that the testing procedure can cope with heteroscedastic errors and no replicates. Recursive formulae allowing one to calculate the exact distribution of the test statistic under the null hypothesis and under a class of alternative hypotheses are given.     

Robust tests based on dual divergence estimators and saddlepoint approximations

This paper is devoted to robust hypothesis testing based on saddlepoint approximations in the framework of general parametric models. As is known, two main problems can arise when using classical tests. First, the models are approximations of reality and slight deviations from them can lead to unreliable results when using classical tests based on these models. Then, even if a model is correctly chosen, the classical tests are based on first order asymptotic theory. This can lead to inaccurate p-values when the sample size is moderate or small. To overcome these problems, robust tests based on dual divergence estimators and saddlepoint approximations, with good performances in small samples, are proposed.     

A convenient preparation of (1R,2S,7S,8R)-3,5-diaza-2,7-dimethyl-1,8-diphenyloctan-1,8-diol and its enantiomer

The synthesis of (1R,2S,7S,8R)-3,5-diaza-2,7-dimethyl-1,8-diphenyloctan-1,8-diol 6 and its enantiomer 7 are described utilising (-)-(1R,2S)- or (+)-(1S,2R)-norephedrine, respectively.     

Characterization of carbohydrates in mucilage samples from the northern Adriatic Sea

Carbohydrate contents in seawater, mucilage, and mucilage interstitial waters were analyzed during episodes of mucilage formation in the summers of 2000 and 2001 in the northern Adriatic Sea off Pesaro and in the Gulf of Trieste using 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) and 2,4,6-tripyridyl-s-triazine (TPTZ) assays. The significant presence of polysaccharides in seawater in the presence of mucilage has an important impact on the agglomeration processes forming gelatinous material (macrogels). Characterization of oligosaccharides in the water-soluble fraction of mucilage using HPLC/RI revealed maltose and pentaose as the main components.