On the use of partial area under the ROC curve for comparison of two diagnostic tests

Evaluation of diagnostic performance is typically based on the receiver operating characteristic (ROC) curve and the area under the curve (AUC) as its summary index. The partial area under the curve (pAUC) is an alternative index focusing on the range of practical/clinical relevance. One of the problems preventing more frequent use of the pAUC is the perceived loss of efficiency in cases of noncrossing ROC curves. In this paper, we investigated statistical properties of comparisons of two correlated pAUCs. We demonstrated that outside of the classic model there are practically reasonable ROC types for which comparisons of noncrossing concave curves would be more powerful when based on a part of the curve rather than the entire curve. We argue that this phenomenon stems in part from the exclusion of noninformative parts of the ROC curves that resemble straight‐lines. We conducted extensive simulation studies in families of binormal, straight‐line, and bigamma ROC curves. We demonstrated that comparison of pAUCs is statistically more powerful than comparison of full AUCs when ROC curves are close to a “straight line”. For less flat binormal ROC curves an increase in the integration range often leads to a disproportional increase in pAUCs’ difference, thereby contributing to an increase in statistical power. Thus, efficiency of differences in pAUCs of noncrossing ROC curves depends on the shape of the curves, and for families of ROC curves that are nearly straight‐line shaped, such as bigamma ROC curves, there are multiple practical scenarios in which comparisons of pAUCs are preferable.     

Isolation of nitrogen deregulated mutants of erythromycin biosynthesis

Summary Ammonium represses erythromycin synthesis bySaccharopolyspora erythraea and insensitive mutants to this effect were isolated. Six mutants were selected and one of them produces 50% more antibiotic than the wild type in 100 mM NH₄Cl as nitrogen source. Glutamine synthetase and alanine dehydrogenase levels in the mutants were determined and no differences with wild type strain were observed.     

The detection of two antigenic groups among Renibacterium salmoninarum isolates

The analysis of the membrane proteins and their antigenic properties in a group of 14 geographically diverse strains of Renibacterium salmoninarum revealed the existence of antigenic diversity within this species. Eleven isolates, including the type strain ATCC 33209, shared a similar protein profile with a major component of 57 kDa whereas three strains showed a common pattern with a major protein of 30 kDa. The quantitative agglutination tests and Western blotting assays seem to indicate the existence of serological heterogeneity, with two distinct groups being detected.     

Structural Insight of a Trimodular Halophilic Cellulase with a Family 46 Carbohydrate-Binding Module

Cellulases are the key enzymes used in the biofuel industry. A typical cellulase contains a catalytic domain connected to a carbohydrate-binding module (CBM) through a flexible linker. Here we report the structure of an atypical trimodular cellulase which harbors a catalytic domain, a CBM46 domain and a rigid CBM_X domain between them. The catalytic domain shows the features of GH5 family, while the CBM46 domain has a sandwich-like structure. The catalytic domain and the CBM46 domain form an extended substrate binding cleft, within which several tryptophan residues are well exposed. Mutagenesis assays indicate that these residues are essential for the enzymatic activities. Gel affinity electrophoresis shows that these tryptophan residues are involved in the polysaccharide substrate binding. Also, electrostatic potential analysis indicates that almost the entire solvent accessible surface of CelB is negatively charged, which is consistent with the halophilic nature of this enzyme.     

Cytokine-induced cell death in immortalized Schwann cells: roles of nitric oxide and cyclic AMP

Tumor necrosis factor-alpha and interferon-gamma are pleiotropic cytokines that regulate Schwann cell responses during injury and inflammatory demyelination. We have previously shown that cyclic AMP (cAMP)-elevating agents decrease the demyelination and Wallerian degeneration in experimental allergic neuritis. In this study, we examined the role of cAMP in cytokine-mediated signaling in a spontaneously immortal Schwann cell clone (iSC). We found that tumor necrosis factor-alpha and interferon-gamma exert synergistic inhibitory action on Schwann cell viability via the production of nitric oxide (NO) and ceramide (cer). Furthermore, we found that: (i) NO synthase inhibitors attenuate the cytokine-induced cer accumulation and cell death indicating that NO acts upstream of cer; and (ii) cytokine-induced cell death is decreased in iSCs pretreated continuously for 48-72 h with forskolin, an activator of adenylate cyclase. Although forskolin modulates the phosphorylation of ERKs and Akt, it decreases the susceptibility of iSC to cytokines via a separate mechanism operating after NO induction and before cer accumulation. We propose that the protective effect of cAMP-elevating agents in experimental allergic neuritis may be mediated in part via modulation of Schwann cell responses to cytokines.     

The model and algorithm of distributing cooperation profits among operators of urban rail transit under PPP pattern

The financing channels, investors and operators of urban rail transit are becoming more and more diversified, and public private partnership pattern has been increasingly suggested in financing and investment field of urban rail transit in China. The diversification of investors of urban rail transit will no doubt lead to the diversification of operators of urban rail transit network. To legitimately distribute the cooperation profits among operators, a model is developed based on passenger’s path choice behavior by considering travel period, travel time, transfer convenience and the comprehensive proportion of different service types provided by operators. In accordance with the features of urban rail transit network and origin-destination (OD) pairs of transferring among lines of different operators, a scheme of improved rail transit network is proposed. On the basis of the algorithm of breadth-first search and depth-first search, an algorithm of searching effective paths based on backtracking and traversing along the shortest path is established by considering the factor of transfer. Taking the example of Shenzhen’s rail transit network, three typical OD pairs are selected to measure and calculate, compare and analyze by six different conditions. The result shows that travel period, travel time, transfer convenience, and service types provided by operators exert great influence on the distribution of cooperation profits. Therefore, it is advisable to comprehensively consider all of these factors to improve the accuracy of cooperation profits distribution. Moreover, the proposed algorithm can search effective paths efficiently.