Evolution and chemical consequences of lightning-produced NOx observed in the North Atlantic upper troposphere

Airborne observations of NO during the Subsonics Assessment Ozone and Nitrogen Oxides Experiment (SONEX) reveal episodes of high NOx in the upper troposphere believed to be associated with lightning. Linkage to specific periods of lightning activity is possible through back trajectories and data from the National Lightning Detection Network. Lagrangian model calculations are used to explore the evolution of these high NOx plumes over the 1-2 days between their introduction and subsequent sampling by NASA's DC-8 aircraft. Simulations include expected changes in HNO3, H2O2, CH3OOH, HO2, and OH. Depending on the time of injection and dilution rate, initial NOx concentrations are estimated to range from 1 to 7 ppbv. Similar to many previous studies, simulated HNO3 concentrations tend to be greater than observations. Several possible explanations for this difference are explored. H2O2 observations are shown to be consistent with removal in convective activity. While it is possible that upper tropospheric CH3OOH is enhanced by convection, simulations show such increases in CH3OOH can be short-lived (e.g., < 12 hours) with no perceptible trace remaining at the time of sampling. High NO levels further prevent elevated levels of CH3OOH from propagating into increases in H2O2. HO2 is suppressed through reaction with NO in all cases. Simulated increases in OH exceeded a factor of 2 for some cases, but for the highest NOx levels, loss of OH via OH+NO2 offset production from HO2+NO. Additional increases in OH of 30-60% could result from convection of CH3OOH. A final point of discussion concerns how the chemistry within these plumes, their long-range transport, and their potential importance in sustaining background NOx far from source regions present a challenge to global and regional model simulations. Copyright 2000 by the American Geophysical Union

Comparison of multivariate statistical methods for dynamic systems modeling

This is the accepted version of the following article: Barceló, S., Vidal-Puig, S. and Ferrer, A. (2011), Comparison of multivariate statistical methods for dynamic systems modeling. Qual. Reliab. Engng. Int., 27: 107–124, which has been published in final form at http://dx.doi.org/10.1002/qre.1102.In this paper two multivariate statistical methodologies are compared in order to estimate a multi-input multi-output transfer function model in an industrial polymerization process. In these contexts, process variables are usually autocorrelated (i.e. there is time-dependence between observations), posing some problems to classical linear regression models. The two methodologies to be compared are both related to the analyses of multivariate time series: Box-Jenkins methodology and partial least squares time series. Both methodologies are compared keeping in mind different issues, such as the simplicity of the process modeling (i.e. the steps of the identification, estimation and validation of the model), the usefulness of the graphical tools, the goodness of fit, and the parsimony of the estimated models. Real data from a polymerization process are used to illustrate the performance of the methodologies under study. Copyright © 2010 John Wiley & Sons, Ltd.This research was partially supported by the Spanish Government (MICINN) and the European Union (RDE funds) under grant DPI2008-06880-C03-03/DPI.Barceló Cerdá, S.; Vidal Puig, S.; Ferrer, A. (2011). Comparison of multivariate statistical methods for dynamic systems modeling. Quality and Reliability Engineering International. 27(1):107-124. https://doi.org/10.1002/qre.1102S107124271Box, G. E. P., Jenkins, G. M., & Reinsel, G. C. (2008). Time Series Analysis. Wiley Series in Probability and Statistics. doi:10.1002/9781118619193Reinsel, G. C. (1997). Elements of Multivariate Time Series Analysis. Springer Series in Statistics. doi:10.1007/978-1-4612-0679-8Wold, S. (1994). Exponentially weighted moving principal components analysis and projections to latent structures. Chemometrics and Intelligent Laboratory Systems, 23(1), 149-161. doi:10.1016/0169-7439(93)e0075-fWise, B. M., & Ricker, N. L. (1993). Identification of finite impulse response models with continuum regression. Journal of Chemometrics, 7(1), 1-14. doi:10.1002/cem.1180070102Dayal, B. S., & MacGregor, J. F. (1996). Identification of Finite Impulse Response Models:  Methods and Robustness Issues. Industrial & Engineering Chemistry Research, 35(11), 4078-4090. doi:10.1021/ie960180eFerrer, A., Aguado, D., Vidal-Puig, S., Prats, J. M., & Zarzo, M. (2008). PLS: A versatile tool for industrial process improvement and optimization. Applied Stochastic Models in Business and Industry, 24(6), 551-567. doi:10.1002/asmb.716Hannan, E. J. (1971). The Identification Problem for Multiple Equation Systems with Moving Average Errors. Econometrica, 39(5), 751. doi:10.2307/1909577Kohn, R. (1979). Identification Results for Armax Structures. Econometrica, 47(5), 1295. doi:10.2307/1911964Chen, C., & Liu, L.-M. (1993). Joint Estimation of Model Parameters and Outlier Effects in Time Series. Journal of the American Statistical Association, 88(421), 284. doi:10.2307/2290724Box, G. E. P., & MacGregor, J. F. (1974). The Analysis of Closed-Loop Dynamic-Stochastic Systems. Technometrics, 16(3), 391. doi:10.2307/1267669Geladi, P., & Kowalski, B. R. (1986). Partial least-squares regression: a tutorial. Analytica Chimica Acta, 185, 1-17. doi:10.1016/0003-2670(86)80028-9Helland, I. S. (1988). On the structure of partial least squares regression. Communications in Statistics - Simulation and Computation, 17(2), 581-607. doi:10.1080/03610918808812681Höskuldsson, A. (1988). PLS regression methods. Journal of Chemometrics, 2(3), 211-228. doi:10.1002/cem.1180020306Wold, S., Albano, C., Dunn, W. J., Edlund, U., Esbensen, K., Geladi, P., … Sjöström, M. (1984). Multivariate Data Analysis in Chemistry. Chemometrics, 17-95. doi:10.1007/978-94-017-1026-8_

Role of Ca2+ and L-Phe in Regulating Functional Cooperativity of Disease- Associated ‘‘Toggle’’ Calcium-Sensing Receptor Mutations

The Ca2+-sensing receptor (CaSR) regulates Ca2+ homeostasis in the body by monitoring extracellular levels of Ca2+ ([Ca2+]o) and amino acids. Mutations at the hinge region of the N-terminal Venus flytrap domain (VFTD) produce either receptor inactivation (L173P, P221Q) or activation (L173F, P221L) related to hypercalcemic or hypocalcemic disorders. In this paper, we report that both L173P and P221Q markedly impair the functional positive cooperativity of the CaSR as reflected by [Ca2+]o–induced [Ca2+]i oscillations, inositol-1-phosphate (IP1) accumulation and extracellular signal-regulated kinases (ERK1/2) activity. In contrast, L173F and P221L show enhanced responsiveness of these three functional readouts to [Ca2+]o. Further analysis of the dynamics of the VFTD mutants using computational simulation studies supports disruption in the correlated motions in the loss-offunction CaSR mutants, while these motions are enhanced in the gain-of-function mutants. Wild type (WT) CaSR was modulated by L-Phe in a heterotropic positive cooperative way, achieving an EC50 similar to those of the two activating mutations. The response of the inactivating P221Q mutant to [Ca2+]o was partially rescued by L-Phe, illustrating the capacity of the L-Phe binding site to enhance the positive homotropic cooperativity of CaSR. L-Phe had no effect on the other inactivating mutant. Moreover, our results carried out both in silico and in intact cells indicate that residue Leu173, which is close to residues that are part of the L-Phe-binding pocket, exhibited impaired heterotropic cooperativity in the presence of L-Phe. Thus, Pro221 and Leu173 are important for the positive homo- and heterotropic cooperative regulation elicited by agonist binding

c-MYC coordinately regulates ribosomal gene chromatin remodeling and Pol I availability during granulocyte differentiation

Loss of c-MYC is required for downregulation of ribosomal RNA (rRNA) gene (rDNA) transcription by RNA Polymerase I (Pol I) during granulocyte differentiation. Here, we demonstrate a robust reduction of Pol I loading onto rDNA that along with a depletion of the MYC target gene upstream binding factor (UBF) and a switch from epigenetically active to silent rDNA accompanies this MYC reduction. We hypothesized that MYC may coordinate these mechanisms via direct regulation of multiple components of the Pol I transcription apparatus. Using gene expression arrays we identified a ‘regulon’ of Pol I factors that are both downregulated during differentiation and reinduced in differentiated granulocytes upon activation of the MYC-ER transgene. This regulon includes the novel c-MYC target genes RRN3 and POLR1B. Although enforced MYC expression during granulocyte differentiation was sufficient to increase the number of active rRNA genes, its activation in terminally differentiated cells did not alter the active to inactive gene ratio despite increased rDNA transcription. Thus, c-MYC dynamically controls rDNA transcription during granulocytic differentiation through the orchestrated transcriptional regulation of core Pol I factors and epigenetic modulation of number of active rRNA genes

Phenotypic and functional analyses show stem cell-derived hepatocyte-like cells better mimic fetal rather than adult hepatocytes

Background & Aims: Hepatocyte-like cells (HLCs), differentiated from pluripotent stem cells by the use of soluble factors, can model human liver function and toxicity. However, at present HLC maturity and whether any deficit represents a true fetal state or aberrant differentiation is unclear and compounded by comparison to potentially deteriorated adult hepatocytes. Therefore, we generated HLCs from multiple lineages, using two different protocols, for direct comparison with fresh fetal and adult hepatocytes. Methods: Protocols were developed for robust differentiation. Multiple transcript, protein and functional analyses compared HLCs to fresh human fetal and adult hepatocytes. Results: HLCs were comparable to those of other laboratories by multiple parameters. Transcriptional changes during differentiation mimicked human embryogenesis and showed more similarity to pericentral than periportal hepatocytes. Unbiased proteomics demonstrated greater proximity to liver than 30 other human organs or tissues. However, by comparison to fresh material, HLC maturity was proven by transcript, protein and function to be fetal-like and short of the adult phenotype. The expression of 81% phase 1 enzymes in HLCs was significantly upregulated and half were statistically not different from fetal hepatocytes. HLCs secreted albumin and metabolized testosterone (CYP3A) and dextrorphan (CYP2D6) like fetal hepatocytes. In seven bespoke tests, devised by principal components analysis to distinguish fetal from adult hepatocytes, HLCs from two different source laboratories consistently demonstrated fetal characteristics. Conclusions: HLCs from different sources are broadly comparable with unbiased proteomic evidence for faithful differentiation down the liver lineage. This current phenotype mimics human fetal rather than adult hepatocytes

Avian Influenza Outbreaks in Chickens, Bangladesh

To determine the epidemiology of outbreaks of avian influenza A virus (subtypes H5N1, H9N2) in chickens in Bangladesh, we conducted surveys and examined virus isolates. The outbreak began in backyard chickens. Probable sources of infection included egg trays and vehicles from local live bird markets and larger live bird markets

Moment bounds for non-linear functionals of the periodogram

In this paper, we prove the validity of the Edgeworth expansion of the Discrete Fourier transforms of some linear time series. This result is applied to approach moments of non linear functionals of the periodogram. As an illustration, we give an expression of the mean square error of the Geweke and Porter-Hudak estimator of the long memory parameter. We prove that this estimator is rate optimal, extending the result of Giraitis, Robinson, Samarov (1997) from Gaussian to linear processes