Modern Statistical Models and Methods for Estimating Fatigue-Life and Fatigue-Strength Distributions from Experimental Data

Engineers and scientists have been collecting and analyzing fatigue data since the 1800s to ensure the reliability of life-critical structures. Applications include (but are not limited to) bridges, building structures, aircraft and spacecraft components, ships, ground-based vehicles, and medical devices. Engineers need to estimate S-N relationships (Stress or Strain versus Number of cycles to failure), typically with a focus on estimating small quantiles of the fatigue-life distribution. Estimates from this kind of model are used as input to models (e.g., cumulative damage models) that predict failure-time distributions under varying stress patterns. Also, design engineers need to estimate lower-tail quantiles of the closely related fatigue-strength distribution. The history of applying incorrect statistical methods is nearly as long and such practices continue to the present. Examples include treating the applied stress (or strain) as the response and the number of cycles to failure as the explanatory variable in regression analyses (because of the need to estimate strength distributions) and ignoring or otherwise mishandling censored observations (known as runouts in the fatigue literature). The first part of the paper reviews the traditional modeling approach where a fatigue-life model is specified. We then show how this specification induces a corresponding fatigue-strength model. The second part of the paper presents a novel alternative modeling approach where a fatigue-strength model is specified and a corresponding fatigue-life model is induced. We explain and illustrate the important advantages of this new modeling approach.Comment: 93 pages, 27 page

The Angular Trispectra of CMB Temperature and Polarization

We develop the formalism necessary to study four-point functions of the cosmic microwave background (CMB) temperature and polarization fields. We determine the general form of CMB trispectra, with the constraints imposed by the assumption of statistical isotropy of the CMB fields, and derive expressions for their estimators, as well as their Gaussian noise properties. We apply these techniques to initial non-Gaussianity of a form motivated by inflationary models. Due to the large number of four-point configurations, the sensitivity of the trispectra to initial non-Gaussianity approaches that of the temperature bispectrum at high multipole moment. These trispectra techniques will also be useful in the study of secondary anisotropies induced for example by the gravitational lensing of the CMB by the large scale structure of the universe.Comment: 16 pages, 4 figures; typographical errors correcte

Primary Coenzyme Q Deficiency in Pdss2 Mutant Mice Causes Isolated Renal Disease

Coenzyme Q (CoQ) is an essential electron carrier in the respiratory chain whose deficiency has been implicated in a wide variety of human mitochondrial disease manifestations. Its multi-step biosynthesis involves production of polyisoprenoid diphosphate in a reaction that requires the enzymes be encoded by PDSS1 and PDSS2. Homozygous mutations in either of these genes, in humans, lead to severe neuromuscular disease, with nephrotic syndrome seen in PDSS2 deficiency. We now show that a presumed autoimmune kidney disease in mice with the missense Pdss2kd/kd genotype can be attributed to a mitochondrial CoQ biosynthetic defect. Levels of CoQ9 and CoQ10 in kidney homogenates from B6.Pdss2kd/kd mutants were significantly lower than those in B6 control mice. Disease manifestations originate specifically in glomerular podocytes, as renal disease is seen in Podocin/cre,Pdss2loxP/loxP knockout mice but not in conditional knockouts targeted to renal tubular epithelium, monocytes, or hepatocytes. Liver-conditional B6.Alb/cre,Pdss2loxP/loxP knockout mice have no overt disease despite demonstration that their livers have undetectable CoQ9 levels, impaired respiratory capacity, and significantly altered intermediary metabolism as evidenced by transcriptional profiling and amino acid quantitation. These data suggest that disease manifestations of CoQ deficiency relate to tissue-specific respiratory capacity thresholds, with glomerular podocytes displaying the greatest sensitivity to Pdss2 impairment

Spin Correlation in tt-bar Production from pp-bar Collisions at sqrt(s)=1.8 TeV

The D0 collaboration has performed a study of spin correlation in tt-bar production for the process tt-bar to bb-bar W^+W^-, where the W bosons decay to e-nu or mu-nu. A sample of six events was collected during an exposure of the D0 detector to an integrated luminosity of approximately 125 pb^-1 of sqrt{s}=1.8 TeV pp-bar collisions. The standard model (SM) predicts that the short lifetime of the top quark ensures the transmission of any spin information at production to the tt-bar decay products. The degree of spin correlation is characterized by a correlation coefficient k. We find that k>-0.25 at the 68% confidence level, in agreement with the SM prediction of k=0.88.Comment: Submitted to PRL, Added references, minor changes to tex

Measurement of spin correlation in ttbar production using dilepton final states

We measure the correlation between the spin of the top quark and the spin of the anti-top quark in (ttbar -> W+ W- b bbar -> l+ nu b l- nubar bbar) final states produced in ppbar collisions at a center of mass energy sqrt(s)=1.96 TeV, where l is an electron or muon. The data correspond to an integrated luminosity of 5.4 fb-1 and were collected with the D0 detector at the Fermilab Tevatron collider. The correlation is extracted from the angles of the two leptons in the t and tbar rest frames, yielding a correlation strength C= 0.10^{+0.45}_{-0.45}, in agreement with the NLO QCD prediction within two standard deviations, but also in agreement with the no correlation hypothesis.Comment: 10 pages, 3 figures, submitted to PL

Experimental Test of Connector Rotation during DNA Packaging into Bacteriophage ϕ29 Capsids

The bacteriophage ϕ29 generates large forces to compact its double-stranded DNA genome into a protein capsid by means of a portal motor complex. Several mechanical models for the generation of these high forces by the motor complex predict coupling of DNA translocation to rotation of the head-tail connector dodecamer. Putative connector rotation is investigated here by combining the methods of single-molecule force spectroscopy with polarization-sensitive single-molecule fluorescence. In our experiment, we observe motor function in several packaging complexes in parallel using video microscopy of bead position in a magnetic trap. At the same time, we follow the orientation of single fluorophores attached to the portal motor connector. From our data, we can exclude connector rotation with greater than 99% probability and therefore answer a long-standing mechanistic question

Evaluation of the diurnal cycle in the atmospheric boundary layer over land as represented by a variety of single-column models: the second GABLS experiment

Postprint (published version

Increased Mitochondrial Calcium Sensitivity and Abnormal Expression of Innate Immunity Genes Precede Dopaminergic Defects in Pink1-Deficient Mice

BACKGROUND: PTEN-induced kinase 1 (PINK1) is linked to recessive Parkinsonism (EOPD). Pink1 deletion results in impaired dopamine (DA) release and decreased mitochondrial respiration in the striatum of mice. To reveal additional mechanisms of Pink1-related dopaminergic dysfunction, we studied Ca²+ vulnerability of purified brain mitochondria, DA levels and metabolism and whether signaling pathways implicated in Parkinson\u27s disease (PD) display altered activity in the nigrostriatal system of Pink1⁻/⁻ mice. METHODS AND FINDINGS: Purified brain mitochondria of Pink1⁻/⁻ mice showed impaired Ca²+ storage capacity, resulting in increased Ca²+ induced mitochondrial permeability transition (mPT) that was rescued by cyclosporine A. A subpopulation of neurons in the substantia nigra of Pink1⁻/⁻ mice accumulated phospho-c-Jun, showing that Jun N-terminal kinase (JNK) activity is increased. Pink1⁻/⁻ mice 6 months and older displayed reduced DA levels associated with increased DA turnover. Moreover, Pink1⁻/⁻ mice had increased levels of IL-1β, IL-12 and IL-10 in the striatum after peripheral challenge with lipopolysaccharide (LPS), and Pink1⁻/⁻ embryonic fibroblasts showed decreased basal and inflammatory cytokine-induced nuclear factor kappa-β (NF-κB) activity. Quantitative transcriptional profiling in the striatum revealed that Pink1⁻/⁻ mice differentially express genes that (i) are upregulated in animals with experimentally induced dopaminergic lesions, (ii) regulate innate immune responses and/or apoptosis and (iii) promote axonal regeneration and sprouting. CONCLUSIONS: Increased mitochondrial Ca²+ sensitivity and JNK activity are early defects in Pink1⁻/⁻ mice that precede reduced DA levels and abnormal DA homeostasis and may contribute to neuronal dysfunction in familial PD. Differential gene expression in the nigrostriatal system of Pink1⁻/⁻ mice supports early dopaminergic dysfunction and shows that Pink1 deletion causes aberrant expression of genes that regulate innate immune responses. While some differentially expressed genes may mitigate neurodegeneration, increased LPS-induced brain cytokine expression and impaired cytokine-induced NF-κB activation may predispose neurons of Pink1⁻/⁻ mice to inflammation and injury-induced cell death

Methionine Sulfoxide Reductase A (MsrA) Deficient Mycoplasma genitalium Shows Decreased Interactions with Host Cells

Mycoplasma genitalium is an important sexually transmitted pathogen that affects both men and women. In genital-mucosal tissues, it initiates colonization of epithelial cells by attaching itself to host cells via several identified bacterial ligands and host cell surface receptors. We have previously shown that a mutant form of M. genitalium lacking methionine sulfoxide reductase A (MsrA), an antioxidant enzyme which converts oxidized methionine (Met(O)) into methionine (Met), shows decreased viability in infected animals. To gain more insights into the mechanisms by which MsrA controls M. genitalium virulence, we compared the wild-type M. genitalium strain (G37) with an msrA mutant (MS5) strain for their ability to interact with target cervical epithelial cell lines (HeLa and C33A) and THP-1 monocytic cells. Infection of epithelial cell lines with both strains revealed that MS5 was less cytotoxic to HeLa and C33A cell lines than the G37 strain. Also, the MS5 strain was more susceptible to phagocytosis by THP-1 cells than wild type strain (G37). Further, MS5 was less able to induce aggregation and differentiation in THP-1 cells than the wild type strain, as determined by carboxyfluorescein diacetate succinimidyl ester (CFSE) labeling of the cells, followed by counting of cells attached to the culture dish using image analysis. Finally, MS5 was observed to induce less proinflammatory cytokine TNF-α by THP-1 cells than wild type G37 strain. These results indicate that MsrA affects the virulence properties of M. genitalium by modulating its interaction with host cells