643 research outputs found
Initiation context modulates autoregulation of eukaryotic translation initiation factor 1 (eIF1)
The central feature of standard eukaryotic translation initiation is small ribosome subunit loading at the 5′ cap followed by its 5′ to 3′ scanning for a start codon. The preferred start is an AUG codon in an optimal context. Elaborate cellular machinery exists to ensure the fidelity of start codon selection. Eukaryotic initiation factor 1 (eIF1) plays a central role in this process. Here we show that the translation of eIF1 homologs in eukaryotes from diverse taxa involves initiation from an AUG codon in a poor context. Using human eIF1 as a model, we show that this poor context is necessary for an autoregulatory negative feedback loop in which a high level of eIF1 inhibits its own translation, establishing that variability in the stringency of start codon selection is used for gene regulation in eukaryotes. We show that the stringency of start codon selection (preferential utilization of optimal start sites) is increased to a surprising degree by overexpressing eIF1. The capacity for the cellular level of eIF1 to impact initiation through the variable stringency of initiation codon selection likely has significant consequences for the proteome in eukaryotes
Children's Medicines in Tanzania: A National Survey of Administration Practices and Preferences.
The dearth of age-appropriate formulations of many medicines for children poses a major challenge to pediatric therapeutic practice, adherence, and health care delivery worldwide. We provide information on current administration practices of pediatric medicines and describe key stakeholder preferences for new formulation characteristics. We surveyed children aged 6-12 years, parents/caregivers over age 18 with children under age 12, and healthcare workers in 10 regions of Tanzania to determine current pediatric medicine prescription and administration practices as well as preferences for new formulations. Analyses were stratified by setting, pediatric age group, parent/caregiver education, and healthcare worker cadre. Complete data were available for 206 children, 202 parents/caregivers, and 202 healthcare workers. Swallowing oral solid dosage forms whole or crushing/dissolving them and mixing with water were the two most frequently reported methods of administration. Children frequently reported disliking medication taste, and many had vomited doses. Healthcare workers reported medicine availability most significantly influences prescribing practices. Most parents/caregivers and children prefer sweet-tasting medicine. Parents/caregivers and healthcare workers prefer oral liquid dosage forms for young children, and had similar thresholds for the maximum number of oral solid dosage forms children at different ages can take. There are many impediments to acceptable and accurate administration of medicines to children. Current practices are associated with poor tolerability and the potential for under- or over-dosing. Children, parents/caregivers, and healthcare workers in Tanzania have clear preferences for tastes and formulations, which should inform the development, manufacturing, and marketing of pediatric medications for resource-limited settings
Stringency of start codon selection modulates autoregulation of translation initiation factor eIF5
An AUG in an optimal nucleotide context is the preferred translation initiation site in eukaryotic cells. Interactions among translation initiation factors, including eIF1 and eIF5, govern start codon selection. Experiments described here showed that high intracellular eIF5 levels reduced the stringency of start codon selection in human cells. In contrast, high intracellular eIF1 levels increased stringency. High levels of eIF5 induced translation of inhibitory upstream open reading frames (uORFs) in eIF5 mRNA that initiate with AUG codons in conserved poor contexts. This resulted in reduced translation from the downstream eIF5 start codon, indicating that eIF5 autoregulates its own synthesis. As with eIF1, which is also autoregulated through translation initiation, features contributing to eIF5 autoregulation show deep evolutionary conservation. The results obtained provide the basis for a model in which auto- and cross-regulation of eIF5 and eIF1 translation establish a regulatory feedback loop that would stabilize the stringency of start codon selection
Measurements of Flavour Dependent Fragmentation Functions in Z^0 -> qq(bar) Events
Fragmentation functions for charged particles in Z -> qq(bar) events have
been measured for bottom (b), charm (c) and light (uds) quarks as well as for
all flavours together. The results are based on data recorded between 1990 and
1995 using the OPAL detector at LEP. Event samples with different flavour
compositions were formed using reconstructed D* mesons and secondary vertices.
The \xi_p = ln(1/x_E) distributions and the position of their maxima \xi_max
are also presented separately for uds, c and b quark events. The fragmentation
function for b quarks is significantly softer than for uds quarks.Comment: 29 pages, LaTeX, 5 eps figures (and colour figs) included, submitted
to Eur. Phys. J.
Bose-Einstein Correlations in e+e- to W+W- at 172 and 183 GeV
Bose-Einstein correlations between like-charge pions are studied in hadronic
final states produced by e+e- annihilations at center-of-mass energies of 172
and 183 GeV. Three event samples are studied, each dominated by one of the
processes W+W- to qqlnu, W+W- to qqqq, or (Z/g)* to qq. After demonstrating the
existence of Bose-Einstein correlations in W decays, an attempt is made to
determine Bose-Einstein correlations for pions originating from the same W
boson and from different W bosons, as well as for pions from (Z/g)* to qq
events. The following results are obtained for the individual chaoticity
parameters lambda assuming a common source radius R: lambda_same = 0.63 +- 0.19
+- 0.14, lambda_diff = 0.22 +- 0.53 +- 0.14, lambda_Z = 0.47 +- 0.11 +- 0.08, R
= 0.92 +- 0.09 +- 0.09. In each case, the first error is statistical and the
second is systematic. At the current level of statistical precision it is not
established whether Bose-Einstein correlations, between pions from different W
bosons exist or not.Comment: 24 pages, LaTeX, including 6 eps figures, submitted to European
Physical Journal
W+W- production and triple gauge boson couplings at LEP energies up to 183 GeV
A study of W-pair production in e+e- annihilations at Lep2 is presented,
based on 877 W+W- candidates corresponding to an integrated luminosity of 57
pb-1 at sqrt(s) = 183 GeV. Assuming that the angular distributions of the
W-pair production and decay, as well as their branching fractions, are
described by the Standard Model, the W-pair production cross-section is
measured to be 15.43 +- 0.61 (stat.) +- 0.26 (syst.) pb. Assuming lepton
universality and combining with our results from lower centre-of-mass energies,
the W branching fraction to hadrons is determined to be 67.9 +- 1.2 (stat.) +-
0.5 (syst.)%. The number of W-pair candidates and the angular distributions for
each final state (qqlnu,qqqq,lnulnu) are used to determine the triple gauge
boson couplings. After combining these values with our results from lower
centre-of-mass energies we obtain D(kappa_g)=0.11+0.52-0.37,
D(g^z_1)=0.01+0.13-0.12 and lambda=-0.10+0.13-0.12, where the errors include
both statistical and systematic uncertainties and each coupling is determined
setting the other two couplings to the Standard Model value. The fraction of W
bosons produced with a longitudinal polarisation is measured to be
0.242+-0.091(stat.)+-0.023(syst.). All these measurements are consistent with
the Standard Model expectations.Comment: 48 pages, LaTeX, including 13 eps or ps figures, submitted to
European Physical Journal
Bose-Einstein Correlations of Three Charged Pions in Hadronic Z^0 Decays
Bose-Einstein Correlations (BEC) of three identical charged pions were
studied in 4 x 10^6 hadronic Z^0 decays recorded with the OPAL detector at LEP.
The genuine three-pion correlations, corrected for the Coulomb effect, were
separated from the known two-pion correlations by a new subtraction procedure.
A significant genuine three-pion BEC enhancement near threshold was observed
having an emitter source radius of r_3 = 0.580 +/- 0.004 (stat.) +/- 0.029
(syst.) fm and a strength of \lambda_3 = 0.504 +/- 0.010 (stat.) +/- 0.041
(syst.). The Coulomb correction was found to increase the \lambda_3 value by
\~9% and to reduce r_3 by ~6%. The measured \lambda_3 corresponds to a value of
0.707 +/- 0.014 (stat.) +/- 0.078 (syst.) when one takes into account the
three-pion sample purity. A relation between the two-pion and the three-pion
source parameters is discussed.Comment: 19 pages, LaTeX, 5 eps figures included, accepted by Eur. Phys. J.
Search for Neutral Higgs Bosons in e+e- Collisions at sqrt(s) ~189GeV
A search for neutral Higgs bosons has been performed with the OPAL detector
at LEP, using approximately 170 pb-1 of e+e- collision data collected at
sqrt(s)~189GeV. Searches have been performed for the Standard Model (SM)
process e+e- to H0Z0 and the MSSM processes e+e- to H0Z0, A0h0. The searches
are sensitive to the b b-bar and tau antitau decay modes of the Higgs bosons,
and also to the MSSM decay mode h0 to A0A0. OPAL search results at lower
centre-of-mass energies have been incorporated in the limits we set, which are
valid at the 95% confidence level. For the SM Higgs boson, we obtain a lower
mass bound of 91.0 GeV. In the MSSM, our limits are mh>74.8GeV and mA>76.5GeV,
assuming tan(beta)>1, that the mixing of the scalar top quarks is either zero
or maximal, and that the soft SUSY-breaking masses are 1 TeV. For the case of
zero scalar top mixing, we exclude values of tan(beta) between 0.72 and 2.19.Comment: 38 pages, 15 figures, submitted Euro. Phys. J.
Colour reconnection in e+e- -> W+W- at sqrt(s) = 189 - 209 GeV
The effects of the final state interaction phenomenon known as colour
reconnection are investigated at centre-of-mass energies in the range sqrt(s) ~
189-209 GeV using the OPAL detector at LEP. Colour reconnection is expected to
affect observables based on charged particles in hadronic decays of W+W-.
Measurements of inclusive charged particle multiplicities, and of their angular
distribution with respect to the four jet axes of the events, are used to test
models of colour reconnection. The data are found to exclude extreme scenarios
of the Sjostrand-Khoze Type I (SK-I) model and are compatible with other
models, both with and without colour reconnection effects. In the context of
the SK-I model, the best agreement with data is obtained for a reconnection
probability of 37%. Assuming no colour reconnection, the charged particle
multiplicity in hadronically decaying W bosons is measured to be (nqqch) =
19.38+-0.05(stat.)+-0.08 (syst.).Comment: 30 pages, 9 figures, Submitted to Euro. Phys. J.
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