FolX from Pseudomonas aeruginosa is octameric in both crystal and solution

FolX encodes an epimerase that forms one step of the tetrahydrofolate biosynthetic pathway, which is of interest as it is an established target for important drugs. Here we report the crystal structure of FolX from the bacterial opportunistic pathogen Pseudomonas aeruginosa, as well as a detailed analysis of the protein in solution, using analytical ultracentrifugation (AUC) and small-angle X-ray scattering (SAXS). In combination, these techniques confirm that the protein is an octamer both in the crystal structure, and in solution

Using Scalars to Probe Theories of Low Scale Quantum Gravity

Arkani-Hamed, Dimopoulos and Dvali have recently suggested that gravity may become strong at energies near 1 TeV which would remove the hierarchy problem. Such a scenario can be tested at present and future colliders since the exchange of towers of Kaluza-Klein gravitons leads to a set of new dimension-8 operators that can play important phenomenological roles. In this paper we examine how the production of pairs of scalars at $e^+e^-$, $\gamma \gamma$ and hadron colliders can be used to further probe the effects of graviton tower exchange. In particular we examine the tree-level production of pairs of identical Higgs fields which occurs only at the loop level in both the Standard Model and its extension to the Minimal Supersymmetric Standard Model. Cross sections for such processes are found to be potentially large at the LHC and the next generation of linear colliders. For the $\gamma\gamma$ case the role of polarization in improving sensitivity to graviton exchange is emphasized.Comment: 32 pages, 12 figures, latex, remarks added to tex

Using an Observational Framework to investigate adult language input to young children in a naturalistic environment

The correlation between the communicative intent of parents, in terms of their expectation of a response and the response patterns of young children aged 23—25 months during parent—child interactions, was investigated. An Observational Framework was used to code these parameters in interactions between 36 children and their mothers. The children were assigned by cluster analysis to `advanced', `typical' and `delayed' language groups and their responses were coded with respect to the degree of correctness or appropriateness within the interaction. Differences in both the parental response expectations and the children's response patterns across the three clusters are discussed

Changes in Serological Immunology Measures in UK and Kenyan Adults Post-controlled Human Malaria Infection.

Background: The timing of infection is closely determined in controlled human malaria infection (CHMI) studies, and as such they provide a unique opportunity to dissect changes in immunological responses before and after a single infection. The first Kenyan Challenge Study (KCS) (Pan African Clinical Trial Registry: PACTR20121100033272) was performed in 2013 with the aim of establishing the CHMI model in Kenya. This study used aseptic, cryopreserved, attenuated Plasmodium falciparum sporozoites administered by needle and syringe (PfSPZ Challenge) and was the first to evaluate parasite dynamics post-CHMI in individuals with varying degrees of prior exposure to malaria. Methods: We describe detailed serological and functional immunological responses pre- and post-CHMI for participants in the KCS and compare these with those from malaria-naïve UK volunteers who also underwent CHMI (VAC049) (ClinicalTrials.gov NCT01465048) using PfSPZ Challenge. We assessed antibody responses to three key blood-stage merozoite antigens [merozoite surface protein 1 (MSP1), apical membrane protein 1 (AMA1), and reticulocyte-binding protein homolog 5 (RH5)] and functional activity using two candidate measures of anti-merozoite immunity; the growth inhibition activity (GIA) assay and the antibody-dependent respiratory burst activity (ADRB) assay. Results:Clear serological differences were observed pre- and post-CHMI by ELISA between malaria-naïve UK volunteers in VAC049, and Kenyan volunteers who had prior malaria exposure. Antibodies to AMA1 and schizont extract correlated with parasite multiplication rate (PMR) post-CHMI in KCS. Serum from volunteer 110 in KCS, who demonstrated a dramatically reduced PMR in vivo, had no in vitro GIA prior to CHMI but the highest level of ADRB activity. A significant difference in ADRB activity was seen between KCS volunteers with minimal and definite prior exposure to malaria and significant increases were seen in ADRB activity post-CHMI in Kenyan volunteers. Quinine and atovaquone/proguanil, previously assumed to be removed by IgG purification, were identified as likely giving rise to aberrantly high in vitro GIA results. Conclusions: The ADRB activity assay is a promising functional assay that warrants further investigation as a measure of prior exposure to malaria and predictor of control of parasite growth. The CHMI model can be used to evaluate potential measures of naturally-acquired immunity to malaria

Colossal dielectric constants in transition-metal oxides

Many transition-metal oxides show very large ("colossal") magnitudes of the dielectric constant and thus have immense potential for applications in modern microelectronics and for the development of new capacitance-based energy-storage devices. In the present work, we thoroughly discuss the mechanisms that can lead to colossal values of the dielectric constant, especially emphasising effects generated by external and internal interfaces, including electronic phase separation. In addition, we provide a detailed overview and discussion of the dielectric properties of CaCu3Ti4O12 and related systems, which is today's most investigated material with colossal dielectric constant. Also a variety of further transition-metal oxides with large dielectric constants are treated in detail, among them the system La2-xSrxNiO4 where electronic phase separation may play a role in the generation of a colossal dielectric constant.Comment: 31 pages, 18 figures, submitted to Eur. Phys. J. for publication in the Special Topics volume "Cooperative Phenomena in Solids: Metal-Insulator Transitions and Ordering of Microscopic Degrees of Freedom

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results:Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95 confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion:Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. © 2014 Cancer Research UK

Global Evolution of Obesity Research in Children and Youths: Setting Priorities for Interventions and Policies

Background: Childhood obesity has become a major global epidemic that causes substantial social and health burdens worldwide. The effectiveness of childhood obesity control and prevention depends largely on understanding the issue, including its current development and associated factors in a contextualized perspective. Objectives: Our study aimed to gauge this kind of understanding. Methods: We systematically searched the Web of Science database for studies concerning child obesity published up to 2017 and analyzed the volume of publications, growth rates, impact scores, collaborations, authors, affiliations, and journals. A total of 57,444 research papers were included. Results: The three subject categories with the highest number of papers (over 3,000) were (1) nutrition and dietetics, (2) pediatrics, and (3) public, environmental, and occupational health. We found a dramatic increase in the amount of scientific literature on childhood obesity in the past one or two decades, led by scholars from the USA – ranking at the top regarding the total number of papers (23,965 papers; 30.8%) and total number of citations (859,793 citations) – and multiple Western countries where the obesity epidemic is prevalent. Conclusions: The findings highlight the need for improving international and local research capacities and collaboration to accelerate knowledge production and translation into contextualized and effective childhood obesity prevention

Observation of hard scattering in photoproduction events with a large rapidity gap at HERA

Events with a large rapidity gap and total transverse energy greater than 5 GeV have been observed in quasi-real photoproduction at HERA with the ZEUS detector. The distribution of these events as a function of the $\gamma p$ centre of mass energy is consistent with diffractive scattering. For total transverse energies above 12 GeV, the hadronic final states show predominantly a two-jet structure with each jet having a transverse energy greater than 4 GeV. For the two-jet events, little energy flow is found outside the jets. This observation is consistent with the hard scattering of a quasi-real photon with a colourless object in the proton.Comment: 19 pages, latex, 4 figures appended as uuencoded fil

Time-integrated luminosity recorded by the BABAR detector at the PEP-II e+e- collider

This article is the Preprint version of the final published artcile which can be accessed at the link below.We describe a measurement of the time-integrated luminosity of the data collected by the BABAR experiment at the PEP-II asymmetric-energy e+e- collider at the ϒ(4S), ϒ(3S), and ϒ(2S) resonances and in a continuum region below each resonance. We measure the time-integrated luminosity by counting e+e-→e+e- and (for the ϒ(4S) only) e+e-→μ+μ- candidate events, allowing additional photons in the final state. We use data-corrected simulation to determine the cross-sections and reconstruction efficiencies for these processes, as well as the major backgrounds. Due to the large cross-sections of e+e-→e+e- and e+e-→μ+μ-, the statistical uncertainties of the measurement are substantially smaller than the systematic uncertainties. The dominant systematic uncertainties are due to observed differences between data and simulation, as well as uncertainties on the cross-sections. For data collected on the ϒ(3S) and ϒ(2S) resonances, an additional uncertainty arises due to ϒ→e+e-X background. For data collected off the ϒ resonances, we estimate an additional uncertainty due to time dependent efficiency variations, which can affect the short off-resonance runs. The relative uncertainties on the luminosities of the on-resonance (off-resonance) samples are 0.43% (0.43%) for the ϒ(4S), 0.58% (0.72%) for the ϒ(3S), and 0.68% (0.88%) for the ϒ(2S).This work is supported by the US Department of Energy and National Science Foundation, the Natural Sciences and Engineering Research Council (Canada), the Commissariat à l’Energie Atomique and Institut National de Physique Nucléaire et de Physiquedes Particules (France), the Bundesministerium für Bildung und Forschung and Deutsche Forschungsgemeinschaft (Germany), the Istituto Nazionale di Fisica Nucleare (Italy), the Foundation for Fundamental Research on Matter (The Netherlands), the Research Council of Norway, the Ministry of Education and Science of the Russian Federation, Ministerio de Ciencia e Innovación (Spain), and the Science and Technology Facilities Council (United Kingdom). Individuals have received support from the Marie-Curie IEF program (European Union) and the A.P. Sloan Foundation (USA)

D* Production in Deep Inelastic Scattering at HERA

This paper presents measurements of D^{*\pm} production in deep inelastic scattering from collisions between 27.5 GeV positrons and 820 GeV protons. The data have been taken with the ZEUS detector at HERA. The decay channel $D^{*+}\to (D^0 \to K^- \pi^+) \pi^+$ (+ c.c.) has been used in the study. The $e^+p$ cross section for inclusive D^{*\pm} production with $5<Q^2<100 GeV^2$ and $y<0.7$ is 5.3 \pms 1.0 \pms 0.8 nb in the kinematic region {$1.3<p_T(D^{*\pm})<9.0$ GeV and $| \eta(D^{*\pm}) |<1.5$}. Differential cross sections as functions of p_T(D^{*\pm}), $\eta(D^{*\pm}), W$ and $Q^2$ are compared with next-to-leading order QCD calculations based on the photon-gluon fusion production mechanism. After an extrapolation of the cross section to the full kinematic region in p_T(D^{*\pm}) and $\eta$(D^{*\pm}), the charm contribution $F_2^{c\bar{c}}(x,Q^2)$ to the proton structure function is determined for Bjorken $x$ between 2 $\cdot$ 10$^{-4}$ and 5 $\cdot$ 10$^{-3}$.Comment: 17 pages including 4 figure