Quantal And Classical Correspondence Of Double Scattering

Electron emission from atom-atom collisions is analyzed within the framework, of both quantal and classical dynamics. We examine the effect of explicit electron-electron (e-e) interactions on the ejected electron spectra in hard collisions involving simultaneous excitation and ionization in the collision of two structured atoms. A double scattering sequence represented by a second order Bom approximation has been shown to give a dominant contribution over the single scattering to projectile ionization. A classical simulation confirms the double scattering process is analogous to the Thomas two-step capture mechanism. We find good agreement between quantal and classical calculations, showing the convergence of the Bom series to second order and the possibility of a classical treatment for e-e interactions in non-perturbative regimes. We also find that the shape of the ejected electron spectrum is very different from the usually assumed Lorentzian distribution. © 1993 IOP Publishing Ltd

Towards a genome-scale metabolic model for the Kluyveromyces lactis yeast

The interest in Kluyveromyces lactis (K. lactis) has begun in academia due to its ability to metabolize the betaglycoside (1). Since then, this yeast has been considered a model organism for studies in genetics and physiology (2). This yeast had its genome sequenced back in 2004 (3) and recently we have published a full metabolic re-annotation of its genome (4). This re-annotation can be used, among other applications, to reconstruct genome-scale metabolic models. These models allow anticipating a given organism's phenotype from its genome sequence. The reconstruction of biochemical networks is, currently, a valid alternative to microorganisms modelling as the output provided by the in silico simulations permits focusing on experiments with promising results. Thus, we propose a new fully compartmentalised genome-scale metabolic model for K. lactis, the iOD1759 which comprises 1759 metabolic genes

Reconstructing genome-scale metabolic models with Merlin

The reconstruction of genome-scale metabolic models is based on the well-known stoichiometry of biochemical reactions. Usually the main objective of a reconstruction is the in silico simulation of the phenotypic behaviour of a microorganism, under different environmental and genetic conditions, thus representing an important tool in Metabolic Engineering. The genome of the yeast Kluyveromyces lactis was used as a case study for this method, providing information for the first stage of the reconstruction of this eukaryote. Given and input of 5085 gene sequences, Merlin identified more than 4200 distinct organisms and approximately 394.000 genes with sequence similarities to the K. lactis genome. This information, after user appraisal, will be used to assemble a metabolic model with the reactions catalysed by the enzymes encoded in the genome. Such model, in the SBML format, can be used as a first raw approach to the study of the K. lactis metabolism

Genome-wide metabolic (re-) annotation of Kluyveromyces lactis

Even before having its genome sequence published in 2004, Kluyveromyces lactis had long been considered a model organism for studies in genetics and physiology. Research on Kluyveromyces lactis is quite advanced and this yeast species is one of the few with which it is possible to perform formal genetic analysis. Nevertheless, until now, no complete metabolic functional annotation has been performed to the proteins encoded in the Kluyveromyces lactis genome. Results In this work, a new metabolic genome-wide functional re-annotation of the proteins encoded in the Kluyveromyces lactis genome was performed, resulting in the annotation of 1759 genes with metabolic functions, and the development of a methodology supported by merlin (software developed in-house). The new annotation includes novelties, such as the assignment of transporter superfamily numbers to genes identified as transporter proteins. Thus, the genes annotated with metabolic functions could be exclusively enzymatic (1410 genes), transporter proteins encoding genes (301 genes) or have both metabolic activities (48 genes). The new annotation produced by this work largely surpassed the Kluyveromyces lactis currently available annotations. A comparison with KEGG's annotation revealed a match with 844 (~90%) of the genes annotated by KEGG, while adding 850 new gene annotations. Moreover, there are 32 genes with annotations different from KEGG. Conclusions The methodology developed throughout this work can be used to re-annotate any yeast or, with a little tweak of the reference organism, the proteins encoded in any sequenced genome. The new annotation provided by this study offers basic knowledge which might be useful for the scientific community working on this model yeast, because new functions have been identified for the so-called metabolic genes. Furthermore, it served as the basis for the reconstruction of a compartmentalized, genome-scale metabolic model of Kluyveromyces lactis, which is currently being finished.This work was partially supported by the MIT-Portugal Program in Bioengineering (MIT-Pt/BS-BB/0082/2008) and a PhD grant (SFRH / BD / 47307 / 2008) from Portuguese FCT (Fundacao para a Ciencia e Tecnologia)

Valganciclovir inhibits human adenovirus replication and pathology in permissive immunosuppressed female and male Syrian hamsters

Adenovirus infections of immunocompromised pediatric hematopoietic stem cell transplant patients can develop into serious and often deadly multi-organ disease. There are no drugs approved for adenovirus infections. Cidofovir (an analog of 2-deoxycytidine monophosphate) is used at times but it can be nephrotoxic and its efficacy has not been proven in clinical trials. Brincidofovir, a promising lipid-linked derivative of cidofovir, is in clinical trials. Ganciclovir, an analog of 2-deoxyguanosine, has been employed occasionally but with unknown efficacy in the clinic. In this study, we evaluated valganciclovir against disseminated adenovirus type 5 (Ad5) infection in our permissive immunosuppressed Syrian hamster model. We administered valganciclovir prophylactically, beginning 12 h pre-infection or therapeutically starting at Day 1, 2, 3, or 4 post-infection. Valganciclovir significantly increased survival, reduced viral replication in the liver, and mitigated the pathology associated with Ad5 infection. In cultured cells, valganciclovir inhibited Ad5 DNA replication and blocked the transition from early to late stage of infection. Valganciclovir directly inhibited Ad5 DNA polymerase in vitro, which may explain, at least in part, its mechanism of action. Ganciclovir and valganciclovir are approved to treat infections by certain herpesviruses. Our results support the use of valganciclovir to treat disseminated adenovirus infections in immunosuppressed patients

iOD962 - the first genome-scale metabolic model of Kluyveromyces lactis

The genome-scale metabolic model of Kluyveromyces lactis was reconstructed from its genome annotation. The result was the partially compartmentalized (5 compartments) iOD962 metabolic model composed of 2038 reactions and 1561 metabolites. Previous chemostate experiments were used to adjust the maintenance ATP parameter, and the model proved valuable when predicting the biomass, oxygen and carbon dioxide yields. Also, the in silico knockouts predicted accurately the in vivo phenotypes, when compared to published experiments. This model allowed determining a minimal medium for cultivating K. lactis and will surely allow elucidating insights on the milk yeast metabolism as well as identifying engineering targets for the improvement of the production of by-products of interest by performing in silico simulations

Fast Methods for Jackknifing Inequality Indices

The jackknife is a resampling method that uses subsets of the original database by leaving out one observation at a time from the sample. The paper outlines a procedure to obtain jackknife estimates for several inequality indices with only a few passes through the data. The number of passes is independent of the number of observations. Hence, the method provides an efficient way to obtain standard errors of the estimators even if sample size is large. We apply our method using micro data on individual incomes for Germany and the US

Changes in children’s cognitive development at the Start of School in England 2001–2008.

Since 1997, England has seen massive changes in the Early Years including the introduction of an early childhood curriculum, free pre-school education for three-year-olds and local programmes for disadvantaged communities. Many of these initiatives took time to introduce and become established. Beginning in 2001, and each year thereafter until 2008, the authors collected consistent data from thousands of children when they started school at the age of four on a range of variables, chosen because they are good predictors of later success. These included vocabulary, early reading and early mathematics. Children from the same set of 472 state primary schools in England were assessed each year. This paper contributes to the existing studies of educational trends over time by examining the extent to which children's scores on these measures changed over that period; in general, they were found to have remained stable

Rossby wave dynamics of the North Pacific extra-tropical response to El Niño: importance of the basic state in coupled GCMs

The extra-tropical response to El Nino in a "low" horizontal resolution coupled climate model, typical of the Intergovernmental Panel on Climate Change fourth assessment report simulations, is shown to have serious systematic errors. A high resolution configuration of the same model has a much improved response that is similar to observations. The errors in the low resolution model are traced to an incorrect representation of the atmospheric teleconnection mechanism that controls the extra-tropical sea surface temperatures (SSTs) during El Nino. This is due to an unrealistic atmospheric mean state, which changes the propagation characteristics of Rossby waves. These erroneous upper tropospheric circulation anomalies then induce erroneous surface circulation features over the North Pacific. The associated surface wind speed and direction errors create erroneous surface flux and upwelling anomalies which finally lead to the incorrect extra-tropical SST response to El Nino in the low resolution model. This highlights the sensitivity of the climate response to a single link in a chain of complex climatic processes. The correct representation of these processes in the high resolution model indicates the importance of horizontal resolution in resolving such processes