Symmetry-breaking in chiral polymerisation

We propose a model for chiral polymerisation and investigate its symmetric and asymmetric solutions. The model has a source species which decays into left- and right-handed types of monomer, each of which can polymerise to form homochiral chains; these chains are susceptible to `poisoning' by the opposite handed monomer. Homochiral polymers are assumed to influence the proportion of each type of monomer formed from the precursor. We show that for certain parameter values a positive feedback mechanism makes the symmetric steady-state solution unstable. The kinetics of polymer formation are then analysed in the case where the system starts from zero concentrations of monomer and chains. We show that following a long induction time, extremely large concentrations of polymers are formed for a short time, during this time an asymmetry introduced into the system by a random external perturbation may be massively amplified. The system then approaches one of the steady-state solutions described above.Comment: 26pages, 6 Figure

Operation of the GTS-LHC Source for the Hadron Injector at CERN

The GTS-LHC ion source, designed and build by CEA Grenoble, was installed and commissioned at CERN in 2005. Since than the source has delivered oxygen and lead ion beams (O4+ and Pb27+ from the source, Pb54+ from the linac) for the commissioning of the Low Energy Ion Ring (LEIR). Results of this operation and attempts to improve the source performance and reliability, and the linac performance will be presented in this paper

Efficacy of Grazing Stockpiled Perennial Forages for Winter Maintenance of Beef Cows

In a three year study, wintering systems utilizing the grazing of stockpiled perennial hay crop forages or corn crop residues were compared to maintaining cows in a drylot. In the summer of 1992, two cuttings of hay were harvested (June 22 and August 2) from three 10-acre fields containing “Johnstone” endophyte-free tall fescue and “Spreador II” alfalfa, and one cutting of hay was harvested from three 10- acre fields of smooth brome grass. “Arlington” red clover was frost-seeded into the smooth bromegrass fields in 1993 and into tall fescue-alfalfa and smooth bromegrass fields into 1994. Two cuttings of hay were harvested from all fields in subsequent years, and three-year average hay yields for tall fescue-alfalfa and smooth bromegrass-red clover were 4,336 and 3,481 pounds per acre, respectively. Regrowth of the forage following the August hay harvest of each year was accumulated for winter grazing. Following a killing frost in each year, two fields of each stockpiled forage were stocked with cows in midgestation at two acres per cow. Two 10-acre fields of corn crop residues were also stocked at two acres per cow, following the grain harvest. Mean dry matter forage yields at the initiation of grazing were 1,853, 2,173 and 5,797 pounds per acre for fields containing tall fescue-alfalfa, smooth bromegrass-red clover, and cornstalks, respectively. A drylot was stocked with 18 cows in 1992 and 1993 and 10 cows in 1994. All cows were fed hay as necessary to maintain a body condition score of five. During grazing, mean losses of organic matter were -6.4, -7.6, and -10.7 pounds per acre per cow from tall fescue-alfalfa, smooth bromegrass-red clover, and cornstalk fields. Average organic matter loss rates from stockpiled forages due to weathering alone were equal to only 30% of the weathering losses of the corn crop residues. In vitro digestibility of both stockpiled forages and cornstalks decreased at equal rates during grazing each year, with respective annual loss rates of .14, .08, and .06% per day. Cows grazing corn crop residues required an average of 1,321 pounds per cow less hay than cows maintained in the drylot to maintain equivalent body condition during the grazing season. Cows grazing tall fescue-alfalfa or smooth bromegrass-red clover had body weight gains and condition score changes equal to cows maintained in a drylot but required 64% and 62% less harvested hay than cows in the drylot during the grazing season. Over the entire stored forage cows grazing tall fescue-alfalfa and smooth bromegrass-red clover required an average of 2,390 and 2,337 pounds per cow less than those maintained in the drylot. Because less hay was needed to maintain cows grazing stockpiled forages, average annual excesses of 5,629 and 3,868 pounds of hay dry matter per cow remained in the stockpiled tall fescue-alfalfa and smooth bromegrass-red clover systems

Examination of the effect of acute levodopa administration on the loudness dependence of auditory evoked potentials (LDAEP) in humans

Rationale: The loudness dependence of the auditory evoked potential (LDAEP) is considered a noninvasive in vivo marker of central serotonergic functioning in humans. Nevertheless, results of genetic association studies point towards a modulation of this biomarker by dopaminergic neurotransmission. Objective: We examined the effect of dopaminergic modulation on the LDAEP using L-3,4-dihydroxyphenylalanine (levodopa)/benserazide (Madopar®) as a challenge agent in healthy volunteers. Methods: A double-blind placebo-controlled challenge design was chosen. Forty-two healthy participants (21 females and 21 males) underwent two LDAEP measurements, following a baseline LDAEP measurement either placebo or levodopa (levodopa 200mg/benserazide 50mg) were given orally. Changes in the amplitude and dipole source activity of the N1/P2 intensities (60, 70, 80, 90, and 100dB) were analyzed. Results: The participants of neither the levodopa nor the placebo group showed any significant LDAEP alterations compared to the baseline measurement. The test-retest reliability (Cronbachs Alpha) between baseline and intervention was 0.966 in the verum group and 0.759 in the placebo group, respectively. Conclusions: The administration of levodopa showed no effect on the LDAEP. These findings are in line with other trials using dopamine receptor agonist

YeastMine--an integrated data warehouse for Saccharomyces cerevisiae data as a multipurpose tool-kit.

The Saccharomyces Genome Database (SGD; http://www.yeastgenome.org/) provides high-quality curated genomic, genetic, and molecular information on the genes and their products of the budding yeast Saccharomyces cerevisiae. To accommodate the increasingly complex, diverse needs of researchers for searching and comparing data, SGD has implemented InterMine (http://www.InterMine.org), an open source data warehouse system with a sophisticated querying interface, to create YeastMine (http://yeastmine.yeastgenome.org). YeastMine is a multifaceted search and retrieval environment that provides access to diverse data types. Searches can be initiated with a list of genes, a list of Gene Ontology terms, or lists of many other data types. The results from queries can be combined for further analysis and saved or downloaded in customizable file formats. Queries themselves can be customized by modifying predefined templates or by creating a new template to access a combination of specific data types. YeastMine offers multiple scenarios in which it can be used such as a powerful search interface, a discovery tool, a curation aid and also a complex database presentation format. DATABASE URL: http://yeastmine.yeastgenome.org

The support model for people with legally modified abilities according to United Nations

Este artículo se basa en una investigación social sobre el sistema de protección jurídica de las personas con algún tipo de discapacidad o en situación de dependencia que se encuentran sometidas a las figuras de tutela o curatela, en aplicación de lo previsto y establecido en el Código Civil Español, en sus artículos 199 y 200, así como en la Ley de Enjuiciamiento Civil. La investigación se plantea como un estudio comparado entre diferentes países de la Unión Europea para ver su adecuación a lo establecido en el artículo 12 de la Convención de Naciones Unidas sobre derechos de las Personas con Discapacidad (en adelante, CDPD) en los procedimientos de incapacitación. Los resultados se analizan sobre la base de modelos técnico-sociales de intervención, los análisis jurídicos y la experiencia adquirida por las Fundación Tutelares de Castilla y León. Se proponen y diseñan algunas alternativas y servicios que pueden mejorar la calidad de vida de las personas adultas incapacitadas judicialmente y el tipo de apoyos que se les puede prestar, de acuerdo a lo establecido en la Convención de Naciones Unidas.This article is based on social research into the system of legal protection for persons with disabilities or in a situation of dependence who are subject to the figures of guardianship or conservatorship pursuant to the provisions in the Spanish Civil Code, sections 199 and 200, as well as the Code of Civil Procedure. The research is presented as a comparative study between different countries of the European Union regarding the adaptation to the provisions of Article 12 of the UN Convention on Rights of Persons with Disabilities (hereinafter CRPD) Incapacitation procedures. The results are analyzed on the basis of technical-social intervention models, legal analysis and the experience of Guardianship Foundations of Castilla y León. Some alternatives and services are proposed and designed that can improve the quality of life of legally incapacitated persons and the type of support that can be provided to them in accordance with the provisions of the United Nations Convention

The catalytic subunit of Plasmodium falciparum casein kinase 2 is essential for gametocytogenesis

Casein kinase 2 (CK2) is a pleiotropic kinase phosphorylating substrates in different cellular compartments in eukaryotes. In the malaria parasite Plasmodium falciparum, PfCK2 is vital for asexual proliferation of blood-stage parasites. Here, we applied CRISPR/Cas9-based gene editing to investigate the function of the PfCK2alpha catalytic subunit in gametocytes, the sexual forms of the parasite that are essential for malaria transmission. We show that PfCK2alpha localizes to the nucleus and cytoplasm in asexual and sexual parasites alike. Conditional knockdown of PfCK2alpha expression prevented the transition of stage IV into transmission-competent stage V gametocytes, whereas the conditional knockout of pfck2a completely blocked gametocyte maturation already at an earlier stage of sexual differentiation. In summary, our results demonstrate that PfCK2alpha is not only essential for asexual but also sexual development of P. falciparum blood-stage parasites and encourage studies exploring PfCK2alpha as a potential target for dual-active antimalarial drugs

The 3-phosphoinositide-dependent protein kinase 1 is an essential upstream activator of protein kinase A in malaria parasites

Cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) signalling is essential for the proliferation of Plasmodium falciparum malaria blood stage parasites. The mechanisms regulating the activity of the catalytic subunit PfPKAc, however, are only partially understood, and PfPKAc function has not been investigated in gametocytes, the sexual blood stage forms that are essential for malaria transmission. By studying a conditional PfPKAc knockdown (cKD) mutant, we confirm the essential role for PfPKAc in erythrocyte invasion by merozoites and show that PfPKAc is involved in regulating gametocyte deformability. We furthermore demonstrate that overexpression of PfPKAc is lethal and kills parasites at the early phase of schizogony. Strikingly, whole genome sequencing (WGS) of parasite mutants selected to tolerate increased PfPKAc expression levels identified missense mutations exclusively in the gene encoding the parasite orthologue of 3-phosphoinositide-dependent protein kinase-1 (PfPDK1). Using targeted mutagenesis, we demonstrate that PfPDK1 is required to activate PfPKAc and that T189 in the PfPKAc activation loop is the crucial target residue in this process. In summary, our results corroborate the importance of tight regulation of PfPKA signalling for parasite survival and imply that PfPDK1 acts as a crucial upstream regulator in this pathway and potential new drug target