The evaluation of the scoring systems: the fixed effects model under known variances.

A number of scoring systems for proficiency testing and interlaboratory comparison are in use by the metrology community. The choice of scoring system for a given study is often based on the study coordinator's experience and anecdotal knowledge, perhaps attributable to a historic lack of detailed and formal explanation about the foundation of these systems. This has influenced the development of new scoring systems, some of them departing from the well-established hypothesis testing theory. Often, different scoring systems give different results not because one may be better than the others but because, as they are documented, the user cannot control the confidence level of the test. We present a formal evaluation of seven of these systems under the fixed effects model assuming known variances. Under these sound assumptions, the systems analyzed all have the same statistical properties. Furthermore, these systems are all members of a family of systems based on strictly increasing functions in which the statistical decision problem is invariant. Under the fixed effects model with known variances, no unbiased scoring system can provide greater statistical power than the members of this family of systems. We apply these results to the lead content of water example provided in International Standard ISO 13528:2015 "Statistical methods for use in proficiency testing by interlaboratory comparisons."

Pyrimidine Metabolism: Dynamic and Versatile Pathways in Pathogens and Cellular Development.

The importance of pyrimidines lies in the fact that they are structural components of a broad spectrum of key molecules that participate in diverse cellular functions, such as synthesis of DNA, RNA, lipids, and carbohydrates. Pyrimidine metabolism encompasses all enzymes involved in the synthesis, degradation, salvage, interconversion and transport of these molecules. In this review, we summarize recent publications that document how pyrimidine metabolism changes under a variety of conditions, including, when possible, those studies based on techniques of genomics, transcriptomics, proteomics, and metabolomics. First, we briefly look at the dynamics of pyrimidine metabolism during nonpathogenic cellular events. We then focus on changes that pathogen infections cause in the pyrimidine metabolism of their host. Next, we discuss the effects of antimetabolites and inhibitors, and finally we consider the consequences of genetic manipulations, such as knock-downs, knock-outs, and knock-ins, of pyrimidine enzymes on pyrimidine metabolism in the cell.

De novo pyrimidine biosynthesis in the oomycete plant pathogen Phytophthora infestans.

The oomycete Phytophthora infestans, causal agent of the tomato and potato late blight, generates important economic and environmental losses worldwide. As current control strategies are becoming less effective, there is a need for studies on oomycete metabolism to help identify promising and more effective targets for chemical control. The pyrimidine pathways are attractive metabolic targets to combat tumors, virus and parasitic diseases but have not yet been studied in Phytophthora. Pyrimidines are involved in several critical cellular processes and play structural, metabolic and regulatory functions. Here, we used genomic and transcriptomic information to survey the pyrimidine metabolism during the P. infestans life cycle. After assessing the putative gene machinery for pyrimidine salvage and de novo synthesis, we inferred genealogies for each enzymatic domain in the latter pathway, which displayed a mosaic origin. The last two enzymes of the pathway, orotate phosphoribosyltransferase and orotidine-5-monophosphate decarboxylase, are fused in a multi-domain enzyme and are duplicated in some P. infestans strains. Two splice variants of the third gene (dihydroorotase) were identified, one of them encoding a premature stop codon generating a non-functional truncated protein. Relative expression profiles of pyrimidine biosynthesis genes were evaluated by qRT-PCR during infection in Solanum phureja. The third and fifth genes involved in this pathway showed high up-regulation during biotrophic stages and down-regulation during necrotrophy, whereas the uracil phosphoribosyl transferase gene involved in pyrimidine salvage showed the inverse behavior. These findings suggest the importance of de novo pyrimidine biosynthesis during the fast replicative early infection stages and highlight the dynamics of the metabolism associated with the hemibiotrophic life style of pathogen.