Reliability training

Discussed here is failure physics, the study of how products, hardware, software, and systems fail and what can be done about it. The intent is to impart useful information, to extend the limits of production capability, and to assist in achieving low cost reliable products. A review of reliability for the years 1940 to 2000 is given. Next, a review of mathematics is given as well as a description of what elements contribute to product failures. Basic reliability theory and the disciplines that allow us to control and eliminate failures are elucidated

Phase transitions in social networks

We study a model of network with clustering and desired node degree. The original purpose of the model was to describe optimal structures of scientific collaboration in the European Union. The model belongs to the family of exponential random graphs. We show by numerical simulations and analytical considerations how a very simple Hamiltonian can lead to surprisingly complicated and eventful phase diagram.Comment: 8 pages, 8 figure

Analyzing the Mechanisms of Interferon-Induced Apoptosis Using CrmA and Hepatitis C Virus NS5A

AbstractThe dsRNA-dependent protein kinase, PKR, is a key component of interferon (IFN)-mediated anti-viral action and is frequently inhibited by many viruses following infection of the cell. Recently, we have demonstrated that IFN and PKR can sensitize cells to apoptosis predominantly through the FADD/caspase-8 pathway (S. Balachandran, P. C. Roberts, T. Kipperman, K. N. Bhalla, R. W. Compans, D. R. Archer, and G. N. Barber. (2000b) J. Virol. 74, 1513–1523). Given these findings, it is thus plausible that rather than specifically target IFN-inducible genes such as PKR, viruses could also subvert the mechanisms of IFN action, in part, at locations that could block the apoptotic cascade. To explore this possibility, we analyzed whether the poxvirus caspase-8 inhibitor, CrmA, was able to inhibit IFN or PKR/dsRNA-mediated apoptosis. Our findings indicated that CrmA could indeed inhibit apoptosis induced by both viral infection and dsRNA without blocking PKR activity or inhibiting IFN signaling. In contrast HCV-encoded NS5A, a putative inhibitor of PKR, did not appear to inhibit cell death mediated by a number of apoptotic stimuli, including IFN, TRAIL, and etoposide. Our data imply that viral-encoded inhibitors of apoptosis, such as CrmA, can block the innate arms of the immune response, including IFN-mediated apoptosis, and therefore potentially constitute an alternative family of inhibitors of IFN action in the cell

Exclusive diffractive processes and the quark substructure of mesons

Exclusive diffractive processes on the nucleon are investigated within a model in which the quark-nucleon interaction is mediated by Pomeron exchange and the quark substructure of mesons is described within a framework based on the Dyson-Schwinger equations of QCD. The model quark-nucleon interaction has four parameters which are completely determined by high-energy $\pi N$ and $K N$ elastic scattering data. The model is then used to predict vector-meson electroproduction observables. The obtained $\rho$- and $\phi$-meson electroproduction cross sections are in excellent agreement with experimental data. The predicted $q^2$ dependence of $J/\psi$-meson electroproduction also agrees with experimental data. It is shown that confined-quark dynamics play a central role in determining the behavior of the diffractive, vector-meson electroproduction cross section. In particular, the onset of the asymptotic $1/q^4$ behavior of the cross section is determined by a momentum scale that is set by the current-quark masses of the quark and antiquark inside the vector meson. This is the origin of the striking differences between the $q^2$ dependence of $\rho$-, $\phi$- and $J/\psi$-meson electroproduction cross sections observed in recent experiments.Comment: 53 pages, 23 figures, revtex and epsfig. Minor additions to tex

Replication of LDL SWAs hits in PROSPER/PHASE as validation for future (pharmaco)genetic analyses

<p><b>Background:</b> The PHArmacogenetic study of Statins in the Elderly at risk (PHASE) is a genome wide association study in the PROspective Study of Pravastatin in the Elderly at risk for vascular disease (PROSPER) that investigates the genetic variation responsible for the individual variation in drug response to pravastatin. Statins lower LDL-cholesterol in general by 30%, however not in all subjects. Moreover, clinical response is highly variable and adverse effects occur in a minority of patients. In this report we first describe the rationale of the PROSPER/PHASE project and second show that the PROSPER/PHASE study can be used to study pharmacogenetics in the elderly.</p> <p><b>Methods:</b> The genome wide association study (GWAS) was conducted using the Illumina 660K-Quad beadchips following manufacturer's instructions. After a stringent quality control 557,192 SNPs in 5,244 subjects were available for analysis. To maximize the availability of genetic data and coverage of the genome, imputation up to 2.5 million autosomal CEPH HapMap SNPs was performed with MACH imputation software. The GWAS for LDL-cholesterol is assessed with an additive linear regression model in PROBABEL software, adjusted for age, sex, and country of origin to account for population stratification.</p> <p><b>Results:</b> Forty-two SNPs reached the GWAS significant threshold of p = 5.0e-08 in 5 genomic loci (APOE/APOC1; LDLR; FADS2/FEN1; HMGCR; PSRC1/CELSR5). The top SNP (rs445925, chromosome 19) with a p-value of p = 2.8e-30 is located within the APOC1 gene and near the APOE gene. The second top SNP (rs6511720, chromosome 19) with a p-value of p = 5.22e-15 is located within the LDLR gene. All 5 genomic loci were previously associated with LDL-cholesterol levels, no novel loci were identified. Replication in WOSCOPS and CARE confirmed our results.</p> <p><b>Conclusion:</b> With the GWAS in the PROSPER/PHASE study we confirm the previously found genetic associations with LDL-cholesterol levels. With this proof-of-principle study we show that the PROSPER/PHASE study can be used to investigate genetic associations in a similar way to population based studies. The next step of the PROSPER/PHASE study is to identify the genetic variation responsible for the variation in LDL-cholesterol lowering in response to statin treatment in collaboration with other large trials.</p&gt

Water vapour in the atmosphere of a transiting extrasolar planet

Copyright © 2007 Nature Publishing GroupWater is predicted to be among the most abundant (if not the most abundant) molecular species after hydrogen in the atmospheres of close-in extrasolar giant planets ('hot Jupiters'). Several attempts have been made to detect water on such planets, but have either failed to find compelling evidence for it or led to claims that should be taken with caution. Here we report an analysis of recent observations of the hot Jupiter HD 189733b (ref. 6) taken during the transit, when the planet passed in front of its parent star. We find that absorption by water vapour is the most likely cause of the wavelength-dependent variations in the effective radius of the planet at the infrared wavelengths 3.6 mum, 5.8 mum (both ref. 7) and 8 mum (ref. 8). The larger effective radius observed at visible wavelengths may arise from either stellar variability or the presence of clouds/hazes. We explain the report of a non-detection of water on HD 189733b (ref. 4) as being a consequence of the nearly isothermal vertical profile of the planet's atmosphere

Identification of Multiple Subsets of Ventral Interneurons and Differential Distribution along the Rostrocaudal Axis of the Developing Spinal Cord

The spinal cord contains neuronal circuits termed Central Pattern Generators (CPGs) that coordinate rhythmic motor activities. CPG circuits consist of motor neurons and multiple interneuron cell types, many of which are derived from four distinct cardinal classes of ventral interneurons, called V0, V1, V2 and V3. While significant progress has been made on elucidating the molecular and genetic mechanisms that control ventral interneuron differentiation, little is known about their distribution along the antero-posterior axis of the spinal cord and their diversification. Here, we report that V0, V1 and V2 interneurons exhibit distinct organizational patterns at brachial, thoracic and lumbar levels of the developing spinal cord. In addition, we demonstrate that each cardinal class of ventral interneurons can be subdivided into several subsets according to the combinatorial expression of different sets of transcription factors, and that these subsets are differentially distributed along the rostrocaudal axis of the spinal cord. This comprehensive molecular profiling of ventral interneurons provides an important resource for investigating neuronal diversification in the developing spinal cord and for understanding the contribution of specific interneuron subsets on CPG circuits and motor control

Scaling and nonscaling finite-size effects in the Gaussian and the mean spherical model with free boundary conditions

We calculate finite-size effects of the Gaussian model in a L\times \tilde L^{d-1} box geometry with free boundary conditions in one direction and periodic boundary conditions in d-1 directions for 2<d<4. We also consider film geometry (\tilde L \to \infty). Finite-size scaling is found to be valid for d3 but logarithmic deviations from finite-size scaling are found for the free energy and energy density at the Gaussian upper borderline dimension d* =3. The logarithms are related to the vanishing critical exponent 1-\alpha-\nu=(d-3)/2 of the Gaussian surface energy density. The latter has a cusp-like singularity in d>3 dimensions. We show that these properties are the origin of nonscaling finite-size effects in the mean spherical model with free boundary conditions in d>=3 dimensions. At bulk T_c in d=3 dimensions we find an unexpected non-logarithmic violation of finite-size scaling for the susceptibility \chi \sim L^3 of the mean spherical model in film geometry whereas only a logarithmic deviation \chi\sim L^2 \ln L exists for box geometry. The result for film geometry is explained by the existence of the lower borderline dimension d_l = 3, as implied by the Mermin-Wagner theorem, that coincides with the Gaussian upper borderline dimension d*=3. For 3<d<4 we find a power-law violation of scaling \chi \sim L^{d-1} at bulk T_c for box geometry and a nonscaling temperature dependence \chi_{surface} \sim \xi^d of the surface susceptibility above T_c. For 2<d<3 dimensions we show the validity of universal finite-size scaling for the susceptibility of the mean spherical model with free boundary conditions for both box and film geometry and calculate the corresponding universal scaling functions for T>=T_c.Comment: Submitted to Physical Review

A De Novo Mouse Model of C11orf95-RELA Fusion-Driven Ependymoma Identifies Driver Functions in Addition to NF-κB.

The majority of supratentorial ependymomas (ST-ependymomas) have few mutations but frequently display chromothripsis of chromosome 11q that generates a fusion between C11orf95 and RELA (RELAFUS). Neural stem cells transduced with RELAFUSex vivo form ependymomas when implanted in the brain. These tumors display enhanced NF-κB signaling, suggesting that this aberrant signal is the principal mechanism of oncogenesis. However, it is not known whether RELAFUS is sufficient to drive de novo ependymoma tumorigenesis in the brain and, if so, whether these tumors also arise from neural stem cells. We show that RELAFUS drives ST-ependymoma formation from periventricular neural stem cells in mice and that RELAFUS-induced tumorigenesis is likely dependent on a series of cell signaling pathways in addition to NF-κB

Critical dynamics in thin films

Critical dynamics in film geometry is analyzed within the field-theoretical approach. In particular we consider the case of purely relaxational dynamics (Model A) and Dirichlet boundary conditions, corresponding to the so-called ordinary surface universality class on both confining boundaries. The general scaling properties for the linear response and correlation functions and for dynamic Casimir forces are discussed. Within the Gaussian approximation we determine the analytic expressions for the associated universal scaling functions and study quantitatively in detail their qualitative features as well as their various limiting behaviors close to the bulk critical point. In addition we consider the effects of time-dependent fields on the fluctuation-induced dynamic Casimir force and determine analytically the corresponding universal scaling functions and their asymptotic behaviors for two specific instances of instantaneous perturbations. The universal aspects of nonlinear relaxation from an initially ordered state are also discussed emphasizing the different crossovers that occur during this evolution. The model considered is relevant to the critical dynamics of actual uniaxial ferromagnetic films with symmetry-preserving conditions at the confining surfaces and for Monte Carlo simulations of spin system with Glauber dynamics and free boundary conditions.Comment: 64 pages, 21 figure