Rerandomization tests for analyzing correlated data from dental studies

Dental research studies often produce relatively small data sets in which observations are serially or spatially correlated. Rerandomization tests are presented as alternatives to analysis of variance and multivariate analysis for assessing group differences using such data. Rerandomization tests are particularly useful when the investigator is unwilling to make strong assumptions about the nature of the serial correlation or the distribution of the data. Two examples are discussed that demonstrate these techniques.     

Parametric Characteristic Analysis for Generalized Frequency Response Functions of Nonlinear Systems

In order to explicitly reveal the relationship between system frequency response functions and model parameters which define system nonlinearities, and consequently unveil a direct connection from model parameters to system frequency response characteristics, a parametric characteristic analysis approach is proposed for Volterra systems described by a nonlinear differential equation (NDE). The parametric characteristics of the generalized frequency response functions (GFRFs) for the NDE model are established, and some important properties are discussed, which can explicitly reveal what model parameters contribute and how these parameters affect the GFRFs. Based on the parametric characteristic analysis, it is demonstrated how the system frequency domain characteristics are related to the system time domain model parameters and how the output frequency response function can now be determined explicitly with a detailed polynomial structure. These new results provide a significant and novel insight into the analysis and design of nonlinear systems in the frequency domain. Several examples are included to illustrate the results.     

Proteolytic cleavage and activation of PAK2 during UV irradiation-induced apoptosis in A431 cells

Exposure of mammalian cells to ultraviolet (UV) light elicits a cellular response and can also lead to apoptotic cell death. In this report, we show that a 36-kDa myelin basic protein (MBP) kinase detected by an in-gel kinase assay can be dramatically activated during the early stages of UV irradiation-triggered apoptosis of A431 cells. Immunoblot analysis revealed that this 36-kDa MBP kinase could be recognized by an antibody against the C-terminal regions of a family of p21Cdc42/Rac-activated kinases (PAKs). By using this antibody and a PAK2-specific antibody against the N-terminal region of PAK2 as studying tools, we further demonstrated that UV irradiation caused cleavage of PAK2 to generate a 36-kDa C-terminal catalytic fragment and a 30-kDa N-terminal fragment in A431 cells. The appearance of the 36-kDa C-terminal catalytic fragment of PAK2 matched exactly with the activation of the 36-kDa MBP kinase in A431 cells upon UV irradiation. In addition, UV irradiation also led to activation of CPP32/caspase-3, but not ICH-1L/caspase-2 and ICE/caspase-1, in A431 cells and the kinetics of activation of CPP32/caspase-3 appeared to correlate well with that of DNA fragmentation and of cleavage/activation of PAK2, respectively. Moreover, blockage of activation of CPP32/caspase-3 by pretreating the cells with two specific tetrapeptidic inhibitors for caspases (Ac-DEVD-cho and Ac-YVAD-cmk) could significantly attenuate the extent of cleavage/activation of PAK2 induced by UV irradiation. Collectively, the results demonstrate that cleavage and activation of PAK2 can be induced during the early stages of UV irradiation-triggered apoptosis and indicate the involvement of CPP32/caspase-3 in this process.     

Transferable, plasmid-mediated vanB-type glycopeptide resistance in Enterococcus faecium

An approximately 60-kb transferable, vanB-carrying plasmid has been identified in a clinical Enterococcus faecium strain. A similar plasmid has been observed in an unrelated E. faecium strain, suggesting that plasmid transfer of vanB operons occurs in nature and plays a role in the dissemination of VanB-type resistance among strains of E. faecium.     

Age- and gender-related elastin distribution changes in human vocal folds

To elucidate the mechanism of gut hypertrophy observed in rats artificially reared (AR) on milk formulas, the effects of four refined formulas with different ratios of casein (C) and whey protein (W), CW 2:8, CW 4:6, CW 6:4 and CW 8:2, on the gut growth of AR rats were examined. Four groups of pups were infused with each formula through an intragastric cannula from age 5 to 15 days. Each of the four milk formulas showed a different character in the stomach, such as no curd, very soft curd, soft curd and hard curd, in response to an increasing ratio of C:W. There were no significant differences in body weight gain among the AR groups and mother-reared (MR) controls. The stomach growth, in weight, of AR rats increased in response to the increasing ratios of C:W. In comparison with MR controls, hypertrophy of the stomach of AR rats appeared within the formulas with higher proportions of casein than whey protein (CW 6:4 and CW 8:2), but not those with lower proportions (CW 2:8 and CW 4:6). The growth of the small intestine was also related to the increasing ratio of C:W in the formulas. A similar pattern of hypertrophy in the hindgut was seen in AR rats. There was no association between hypertrophy of the gut in AR rats and plasma triiodothyronine. The present results clearly demonstrated that the gut growth of AR rat pups was directly influenced by the diet but not by AR per se, and that hard casein-curd in the stomach might be one cause of gut hypertrophy.     

Seed banks and molecular maps: unlocking genetic potential from the wild

Nearly a century has been spent collecting and preserving genetic diversity in plants. Germplasm banks-living seed collections that serve as repositories of genetic variation-have been established as a source of genes for improving agricultural crops. Genetic linkage maps have made it possible to study the chromosomal locations of genes for improving yield and other complex traits important to agriculture. The tools of genome research may finally unleash the genetic potential of our wild and cultivated germplasm resources for the benefit of society.     

Utility and feasibility of assessing myocardial mechanics after bypass

The authors present the case of a 34-year-old man struck over the left mastoid region by a hockey puck, who suffered a fatal rupture of a left vertebral artery berry aneurysm. He became apneic within seconds of the injury and had no brainstem reflex within minutes. The postmortem examination showed massive subarachnoid hemorrhage in the posterior fossa and the remnants of a berry aneurysm near the intradural origin of the left vertebral artery, 11 mm proximal to the posterior inferior cerebellar artery. Rupture of a saccular aneurysm as a result of head trauma is rare. This is the first reported case of a posterior circulation aneurysm rupture as a result of head trauma.     

Astrocytes are the major source of nerve growth factor upregulation following traumatic brain injury in the rat

A between-side comparison of GABAA receptor subunit expression levels in the globus pallidus and anterior-pole motor thalamic nuclei of rats with an ibotenate lesion of the striatum, and rats receiving a fetal striatal graft in the lesioned area was made by using immunocytochemistry with subunit-specific antibodies, at different times post-lesion or different times post-grafting. At 10 days post-lesion, there was already an increase in the labeling of the alpha 1- and beta 2/3-subunits in the globus pallidus, entopeduncular nucleus and ventrolateral nucleus ipsilateral to the lesion when compared with the contralateral side, while there were no significant changes at the level of the ventromedial nucleus. Labeling of the alpha 2-subunit showed a clear increase in the entopeduncular nucleus compared with the contralateral side at 10 days post-lesion. Similar changes were also observed for the different subunits studied at 30 and 120 days after lesioning. Rats with 20-day old transplants of fetal striatal neurons that were implanted in the ibotenate lesioned striatum at 10 days post-lesioning, continued to show changes in the expression of GABAA receptor subunits, albeit at a lower level than those of ibotenate lesioned rats at similar age post-lesion. However, when examining rats with 70-day old transplants, the ibotenate-lesion induced between-side changes were almost completely compensated. These findings suggest a correlation between the maturation of the grafts and their capability to function in reestablishing neuronal circuits as shown by the reduction of changes in GABAergic transmission induced by ibotenate lesions, as indicated by the reversal of changes in GABAA receptor subunit in several areas of the basal ganglia circuit.     

Measurement of myocardial blood flow with oxygen-15 labelled water: comparison of different administration protocols

Positron emission tomography (PET) in conjunction with C15O2 or H215O can be used to measure myocardial blood flow (MBF) and tissue fraction (TF), i.e. the fraction of the tissue mass in the volume of the region of interest. However, with C15O2 inhalation, the tissue fraction in the septum is overestimated. Bolus injection of H215O together with arterial cannulation gives very precise results but is invasive. The purpose of this study was to develop a method which circumvents these problems. A four-parameter model with parameters for MBF, TF and spill-over fractions from both left and right ventricular cavities was developed. This method was compared with a three-parameter model (no right ventricular cavity spill-over) in both septal and non-septal regions of interest for three different administration protocols: bolus injection of H215O, infusion of H215O and inhalation of C15O2. It was found that MBF can be measured with intravenous administration of H215O without the requirement for arterial cannulation. The four-parameter protocol with bolus injection was stable in clinical studies. The four-parameter model proved essential for the septum, where it gave highly significantly better fits than did the three-parameter model (P<0.00003 in each of 15 subjects). Administration of H215O together with this four-parameter model also circumvented the problem of overestimation of TF in the septum seen with C15O2 inhalation. In addition, the radiation dose of H215O protocols is lower than that of C15O2 inhalation. Using a left atrial input curve instead of a left ventricular cavity input curve gave the same mean MBF and TF.     

Binding of Clostridium difficile toxin A to human milk secretory component

The objective of the present study was to evaluate the effect of the proinflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-alpha (IL-1a), on myoblast proliferation and fusion and on myocyte protein metabolism and stress protein expression. Proliferation was suppressed (p < 0.05) by both cytokines, alone and in combination, and at lower concentrations, the suppression was additive. Likewise, fusion was retarded (p < 0.05) by these cytokines alone and in combination. Myosin synthesis was not altered acutely or chronically by TNF-alpha alone or by the combination of this cytokine with IL-1alpha. Chronic exposure to TNF-alpha did not alter total cellular protein synthesis, but exposure to IL-1alpha and the cytokine combination resulted in an increase (14% to 19%, p < 0.05) in synthesis. Neither total cellular protein nor myosin degradation were influenced by either cytokine alone or by the combination. There was no detectable induction, acutely or chronically, of any of the stress proteins evaluated (HSC70, HSP70, or HSP60). These data suggest that cytokines may alter muscle growth and development prenatally and postnatally and that the changes in muscle protein metabolism during periods of immune challenge are not direct effects of TNF-alpha or IL-1alpha.