Process Capability Database Usage In Industry: Myth vs. Reality

Process capability data (PCD) is needed for robust design, optimal tolerance allocation, and variation simulation analysis. Process capability databases (PCDBs) have been developed in many industries and are being used by the manufacturing community to monitor quality; however, they are not being effectively utilized by design. When the PCDBs1 were developed, the intent was for design to use PCD for optimization and product cost minimization, but this ideal situation has not been realized. A survey of a variety of design and manufacturing companies was circulated to determine both the state-ofthe- art in PCDBs and the barriers preventing design from fully utilizing PCD. Two key barriers were identified for internal PCDBs: lack of a company-wide vision for PCD usage and poor communication between manufacturing and design. Supplier PCDBs have the additional barriers of lack of trust between suppliers and customers and time lag for data entry. Management support, training, database population, and common systems were identified as potential solutions to the identified barriers

Molecular identification of organic vapors driving atmospheric nanoparticle growth

Particles formed in the atmosphere via nucleation provide about half the number of atmospheric cloud condensation nuclei, but in many locations, this process is limited by the growth of the newly formed particles. That growth is often via condensation of organic vapors. Identification of these vapors and their sources is thus fundamental for simulating changes to aerosol-cloud interactions, which are one of the most uncertain aspects of anthropogenic climate forcing. Here we present direct molecular-level observations of a distribution of organic vapors in a forested environment that can explain simultaneously observed atmospheric nanoparticle growth from 3 to 50 nm. Furthermore, the volatility distribution of these vapors is sufficient to explain nanoparticle growth without invoking particle-phase processes. The agreement between observed mass growth, and the growth predicted from the observed mass of condensing vapors in a forested environment thus represents an important step forward in the characterization of atmospheric particle growth.Peer reviewe

Alzheimer's disease-associated R47H TREM2 increases, but wild-type TREM2 decreases, microglial phagocytosis of synaptosomes and neuronal loss

Triggering receptor on myeloid cells 2 (TREM2) is an innate immune receptor, upregulated on the surface of microglia associated with amyloid plaques in Alzheimer's disease (AD). Individuals heterozygous for the R47H variant of TREM2 have greatly increased risk of developing AD. We examined the effects of wild-type (WT), R47H and knock-out (KO) of human TREM2 expression in three microglial cell systems. Addition of mouse BV-2 microglia expressing R47H TREM2 to primary mouse neuronal cultures caused neuronal loss, not observed with WT TREM2. Neuronal loss was prevented by using annexin V to block exposed phosphatidylserine, an eat-me signal and ligand of TREM2, suggesting loss was mediated by microglial phagocytosis of neurons exposing phosphatidylserine. Addition of human CHME-3 microglia expressing R47H TREM2 to LUHMES neuronal-like cells also caused loss compared to WT TREM2. Expression of R47H TREM2 in BV-2 and CHME-3 microglia increased their uptake of phosphatidylserine-beads and synaptosomes versus WT TREM2. Human iPSC-derived microglia with heterozygous R47H TREM2 had increased phagocytosis of synaptosomes vs common-variant TREM2. Additionally, phosphatidylserine liposomes increased activation of human iPSC-derived microglia expressing homozygous R47H TREM2 versus common-variant TREM2. Finally, overexpression of TREM2 in CHME-3 microglia caused increased expression of cystatin F, a cysteine protease inhibitor, and knock-down of cystatin F increased CHME-3 uptake of phosphatidylserine-beads. Together, these data suggest that R47H TREM2 may increase AD risk by increasing phagocytosis of synapses and neurons via greater activation by phosphatidylserine and that WT TREM2 may decrease microglial phagocytosis of synapses and neurons via cystatin F

The Atacama Cosmology Telescope: Two-Season ACTPol Lensing Power Spectrum

We report a measurement of the power spectrum of cosmic microwave background (CMB) lensing from two seasons of Atacama Cosmology Telescope Polarimeter (ACTPol) CMB data. The CMB lensing power spectrum is extracted from both temperature and polarization data using quadratic estimators. We obtain results that are consistent with the expectation from the best-fit Planck LCDM model over a range of multipoles L=80-2100, with an amplitude of lensing A_lens = 1.06 +/- 0.15 (stat.) +/- 0.06 (sys.) relative to Planck. Our measurement of the CMB lensing power spectrum gives sigma_8 Omega_m^0.25 = 0.643 +/- 0.054; including baryon acoustic oscillation scale data, we constrain the amplitude of density fluctuations to be sigma_8 = 0.831 +/- 0.053. We also update constraints on the neutrino mass sum. We verify our lensing measurement with a number of null tests and systematic checks, finding no evidence of significant systematic errors. This measurement relies on a small fraction of the ACTPol data already taken; more precise lensing results can therefore be expected from the full ACTPol dataset.Comment: 17 pages, 11 figures, to be submitted to Physical Review

Causal hierarchy within the thalamo-cortical network in spike and wave discharges

Background: Generalised spike wave (GSW) discharges are the electroencephalographic (EEG) hallmark of absence seizures, clinically characterised by a transitory interruption of ongoing activities and impaired consciousness, occurring during states of reduced awareness. Several theories have been proposed to explain the pathophysiology of GSW discharges and the role of thalamus and cortex as generators. In this work we extend the existing theories by hypothesizing a role for the precuneus, a brain region neglected in previous works on GSW generation but already known to be linked to consciousness and awareness. We analysed fMRI data using dynamic causal modelling (DCM) to investigate the effective connectivity between precuneus, thalamus and prefrontal cortex in patients with GSW discharges. Methodology and Principal Findings: We analysed fMRI data from seven patients affected by Idiopathic Generalized Epilepsy (IGE) with frequent GSW discharges and significant GSW-correlated haemodynamic signal changes in the thalamus, the prefrontal cortex and the precuneus. Using DCM we assessed their effective connectivity, i.e. which region drives another region. Three dynamic causal models were constructed: GSW was modelled as autonomous input to the thalamus (model A), ventromedial prefrontal cortex (model B), and precuneus (model C). Bayesian model comparison revealed Model C (GSW as autonomous input to precuneus), to be the best in 5 patients while model A prevailed in two cases. At the group level model C dominated and at the population-level the p value of model C was ∼1. Conclusion: Our results provide strong evidence that activity in the precuneus gates GSW discharges in the thalamo-(fronto) cortical network. This study is the first demonstration of a causal link between haemodynamic changes in the precuneus - an index of awareness - and the occurrence of pathological discharges in epilepsy. © 2009 Vaudano et al

Redox proteomics of the inflammatory secretome identifies a common set of redoxins and other glutathionylated proteins released in inflammation, influenza virus infection and oxidative stress

Protein cysteines can form transient disulfides with glutathione (GSH), resulting in the production of glutathionylated proteins, and this process is regarded as a mechanism by which the redox state of the cell can regulate protein function. Most studies on redox regulation of immunity have focused on intracellular proteins. In this study we have used redox proteomics to identify those proteins released in glutathionylated form by macrophages stimulated with lipopolysaccharide (LPS) after pre-loading the cells with biotinylated GSH. Of the several proteins identified in the redox secretome, we have selected a number for validation. Proteomic analysis indicated that LPS stimulated the release of peroxiredoxin (PRDX) 1, PRDX2, vimentin (VIM), profilin1 (PFN1) and thioredoxin 1 (TXN1). For PRDX1 and TXN1, we were able to confirm that the released protein is glutathionylated. PRDX1, PRDX2 and TXN1 were also released by the human pulmonary epithelial cell line, A549, infected with influenza virus. The release of the proteins identified was inhibited by the anti-inflammatory glucocorticoid, dexamethasone (DEX), which also inhibited tumor necrosis factor (TNF)-α release, and by thiol antioxidants (N-butanoyl GSH derivative, GSH-C4, and N-acetylcysteine (NAC), which did not affect TNF-α production. The proteins identified could be useful as biomarkers of oxidative stress associated with inflammation, and further studies will be required to investigate if the extracellular forms of these proteins has immunoregulatory functions

Childbirth experience questionnaire: validating its use in the United Kingdom

BACKGROUND: The Childbirth Experience Questionnaire (CEQ) was developed in Sweden in 2010 and validated in 920 primiparous women. It has not been validated in the United Kingdom (UK). Measuring the impact of an intervention on a woman's childbirth experience is arguably as important as measuring its impact on outcomes such as caesarean delivery and perinatal morbidity or mortality and yet surprisingly it is rarely done. The lack of a robust validated tool for evaluating labour experience in the UK is a topical issue in the UK at present. Indeed NICE say 'A standardised method to measure and quantify women's psychological and emotional wellbeing and their birth experiences is urgently required to support any study investigating the effectiveness of interventions, techniques or strategies during birth.' METHODS: The Childbirth Experience Questionnaire and part of the Care Quality Commission Maternity Survey (2010) was sent to 350 women at one month postnatal. The CEQ was sent again two weeks later. The CEQ was tested for face validity among 25 postnatal mothers. Demographic data and delivery data was used to establish construct validity of the CEQ using the method of known-groups validation. The results of the scored CEQ sent out twice were used to measure test-retest reliability of the CEQ by calculating the quadratic weighted index of agreement between the two scores. Criterion validity was measured by calculating the Pearson correlation coefficient for the CEQ and Maternity Survey scores. RESULTS: Face validity of the CEQ in a UK population was demonstrated with all respondents stating it was easy to understand and complete. A statistically significantly higher CEQ score for subgroups of women known to report a better birth outcome demonstrated construct validity of the CEQ. A weighted kappa of 0.68 demonstrated test-retest reliability of the CEQ. A Pearson correlation co-efficient of 0.73 demonstrated a strong correlation between the results of the CEQ and the results of the 'gold standard' assessment of childbirth experience in the UK: the Maternity Survey and hence criterion validity of the CEQ. CONCLUSIONS: The Childbirth Experience Questionnaire is a valid and reliable measure of childbirth experience in the UK population

The Atacama Cosmology Telescope: Two-Season ACTPol Spectra and Parameters

We present the temperature and polarization angular power spectra measured by the Atacama Cosmology Telescope Polarimeter (ACTPol). We analyze night-time data collected during 2013-14 using two detector arrays at 149 GHz, from 548 deg$^2$ of sky on the celestial equator. We use these spectra, and the spectra measured with the MBAC camera on ACT from 2008-10, in combination with Planck and WMAP data to estimate cosmological parameters from the temperature, polarization, and temperature-polarization cross-correlations. We find the new ACTPol data to be consistent with the LCDM model. The ACTPol temperature-polarization cross-spectrum now provides stronger constraints on multiple parameters than the ACTPol temperature spectrum, including the baryon density, the acoustic peak angular scale, and the derived Hubble constant. Adding the new data to planck temperature data tightens the limits on damping tail parameters, for example reducing the joint uncertainty on the number of neutrino species and the primordial helium fraction by 20%.Comment: 23 pages, 25 figure