Effect of streptococcal pyrogenic exotoxin on rabbit macrophage functions in vitro: mediation by splenic lymphocytes

Streptococcal pyrogenic exotoxin (SPE) showed no direct effect on rabbit macrophage functions in vitro. However, when splenic lymphocytes were added to macrophage cultures, SPE caused marked augmentation of glucose consumption and superoxide anion production, and concomitant inhibition of phagocytosis without loss of cell viability. The SPE effects were demonstrated to be mediated by a soluble factor(s) released from the splenic lymphocytes in response to SPE stimulus.     

Sample Size Determination for Grouped Exponential Observations: A Cost Function Approach

Calculating the required sample size for a desired power at a given type I error level, we often assume that we know the exact time of all subject responses whenever they occur during our study period. It is very common, however, in practice that we only monitor subjects periodically and, therefore, we know only whether responses occur or not during an interval. This paper includes a quantitative discussion of the effect resulting from data grouping or interval censoring on the required sample size when we have two treatment groups. Furthermore, with the goal of exploring the optimum in the number of subjects, the number of examinations per subject for test responses, and the total length of a study time period, this paper also provides a general guideline about how to determine these to minimize the total cost of a study for a desired power at a given α-level. A specified linear cost function that incorporates the costs of obtaining subjects, periodic examinations for test responses of subjects, and the total length of a study period, is assumed, primarily for illustrative purpose.     

The synthesis and hepatoprotective activity of esters of the lupane group triterpenoids

Hemisuccinates, hemiphthalates, acetylsalicylates, cinnamates, andp-methoxycinnamates of lupeol, betulin, and 3-O-acetylbetulin were synthesized via interaction with corresponding acid anhydrides or acid chlorides. A number of betulin esters in position 3 and 28 were shown to exhibit a pronounced hepatoprotective effect similar to that of betulin and silibor. These experimental data were in a good agreement with the computer prediction of their biological activity. Betulin 3,28-bishemiphthalate was more effective than carsil in models of experimental hepatitis caused by carbon tetrachloride, tetracycline, and ethanol.     

High resolution genetic mapping uncovers chitin synthase-1 as the target-site of the structurally diverse mite growth inhibitors clofentezine,hexythiazox and etoxazole in Tetranychus urticae

The acaricides clofentezine, hexythiazox and etoxazole are commonly referred to as ‘mite growth inhibitors’, and clofentezine and hexythiazox have been used successfully for the integrated control of plant mite pests for decades. Although they are still important today, their mode of action has remained elusive. Recently, a mutation in chitin synthase 1 (CHS1) was linked to etoxazole resistance. In this study, we identified and investigated a Tetranychus urticae strain (HexR) harboring recessive, monogenic resistance to each of hexythiazox, clofentezine, and etoxazole. To elucidate if there is a common genetic basis for the observed cross-resistance, we adapted a previously developed bulk segregant analysis method to map with high resolution a single, shared resistance locus for all three compounds. This finding indicates that the underlying molecular basis for resistance to all three compounds is identical. This locus is centered on the CHS1 gene, and as supported by additional genetic and biochemical studies, a non-synonymous variant (I1017F) in CHS1 associates with resistance to each of the tested acaricides in HexR. Our findings thus demonstrate a shared molecular mode of action for the chemically diverse mite growth inhibitors clofentezine, hexythiazox and etoxazole as inhibitors of an essential, non-catalytic activity of CHS1. Given the previously documented cross-resistance between clofentezine, hexythiazox and the benzyolphenylurea (BPU) compounds flufenoxuron and cycloxuron, CHS1 should be also considered as a potential target-site of insecticidal BPUs.     

Improved two‐stage group sequential procedures for testing a secondary endpoint after the primary endpoint achieves significance

In two‐stage group sequential trials with a primary and a secondary endpoint, the overall type I error rate for the primary endpoint is often controlled by an α‐level boundary, such as an O'Brien‐Fleming or Pocock boundary. Following a hierarchical testing sequence, the secondary endpoint is tested only if the primary endpoint achieves statistical significance either at an interim analysis or at the final analysis. To control the type I error rate for the secondary endpoint, this is tested using a Bonferroni procedure or any α‐level group sequential method. In comparison with marginal testing, there is an overall power loss for the test of the secondary endpoint since a claim of a positive result depends on the significance of the primary endpoint in the hierarchical testing sequence. We propose two group sequential testing procedures with improved secondary power: the improved Bonferroni procedure and the improved Pocock procedure. The proposed procedures use the correlation between the interim and final statistics for the secondary endpoint while applying graphical approaches to transfer the significance level from the primary endpoint to the secondary endpoint. The procedures control the familywise error rate (FWER) strongly by construction and this is confirmed via simulation. We also compare the proposed procedures with other commonly used group sequential procedures in terms of control of the FWER and the power of rejecting the secondary hypothesis. An example is provided to illustrate the procedures.