A disorder to order transition accompanies catalysis in retinaldehyde dehydrogenase type II

Retinaldehyde dehydrogenase II (RalDH2) converts retinal to the transcriptional regulator retinoic acid in the developing embryo. The x-ray structure of the enzyme revealed an important structural difference between this protein and other aldehyde dehydrogenases of the same enzyme superfamily; a 20-amino acid span in the substrate access channel in retinaldehyde dehydrogenase II is disordered, whereas in other aldehyde dehydrogenases this region forms a well defined wall of the substrate access channel. We asked whether this disordered loop might order during the course of catalysis and provide a means for an enzyme that requires a large substrate access channel to restrict access to the catalytic machinery by smaller compounds that might potentially enter the active site and be metabolized. Our experiments, a combination of kinetic, spectroscopic, and crystallographic techniques, suggest that a disorder to order transition is linked to catalytic activity

Histidine switch controlling pH-dependent protein folding and DNA binding in a transcription factor at the core of synthetic network devices

© 2016 The Royal Society of Chemistry. Therapeutic strategies have been reported that depend on synthetic network devices in which a urate-sensing transcriptional regulator detects pathological levels of urate and triggers production or release of urate oxidase. The transcription factor involved, HucR, is a member of the multiple antibiotic resistance (MarR) protein family. We show that protonation of stacked histidine residues at the pivot point of long helices that form the scaffold of the dimer interface leads to reversible formation of a molten globule state and significantly attenuated DNA binding at physiological temperatures. We also show that binding of urate to symmetrical sites in each protein lobe is communicated via the dimer interface. This is the first demonstration of regulation of a MarR family transcription factor by pH-dependent interconversion between a molten globule and a compact folded state. Our data further suggest that HucR may be utilized in synthetic devices that depend on detection of pH changes

HRTEM of extended defects in Tl-2212 thin films

Many applications of high temperature superconductors, HTS, require the presence of lattice defects in the material structure to suppress the motion of magnetic vortices and enhance the critical current density, J{sub c}. The microstructure of Tl{sub 2}Ba{sub 2}CaCu{sub 2}O{sub 8{minus}{delta}} (Tl-2212) thin films which have extended defects induced by high energy Au and Cu ion irradiation is studied using high resolution transmission electron microscopy, HRTEM, with slow scan digital imaging. In order to optimize the HTS properties and better analyze the consequent microstructural modification, the fluence is varied. At moderate fluences, resulting in {approximately}4% reduction of the superconducting transition, large enhancements of J{sub c} and vortex pinning potential are observed. The density and microstructure of isolated defects and surrounding structure will be discussed and compared to damage profiles calculated using the TRIM code. Correlation will be made between the HRTEM results and the changes in HTS properties

The HADES Tracking System

The tracking system of the dielectron spectrometer HADES at GSI Darmstadt is formed out of 24 low-mass, trapezoidal multi-layer drift chambers providing in total about 30 square meter of active area. Low multiple scattering in the in total four planes of drift chambers before and after the magnetic field is ensured by using helium-based gas mixtures and aluminum cathode and field wires. First in-beam performance results are contrasted with expectations from simulations. Emphasis is placed on the energy loss information, exploring its relevance regarding track recognition.Comment: 6 pages, 4 figures, presented at the 10th Vienna Conference on Instrumentation, Vienna, February 2004, to be published in NIM A (special issue

Creative and Stylistic Devices Employed by Children During a Storybook Narrative Task: A Cross-Cultural Study

Purpose: The purpose of this study was to analyze the effects of culture on the creative and stylistic features children employ when producing narratives based on wordless picture books. Method: Participants included 60 first- and second-grade African American, Latino American, and Caucasian children. A subset of narratives based on wordless picture books collected as part of a larger study was coded and analyzed for the following creative and stylistic conventions: organizational style (topic centered, linear, cyclical), dialogue (direct, indirect), reference to character relationships (nature, naming, conduct), embellishment (fantasy, suspense, conflict), and paralinguistic devices (expressive sounds, exclamatory utterances). Results: Many similarities and differences between ethnic groups were found. No significant differences were found between ethnic groups in organizational style or use of paralinguistic devices. African American children included more fantasy in their stories, Latino children named their characters more often, and Caucasian children made more references to the nature of character relationships. Conclusion: Even within the context of a highly structured narrative task based on wordless picture books, culture influences children’s production of narratives. Enhanced understanding of narrative structure, creativity, and style is necessary to provide ecologically valid narrative assessment and intervention for children from diverse cultural backgrounds

Measurement of the rate of nu_e + d --> p + p + e^- interactions produced by 8B solar neutrinos at the Sudbury Neutrino Observatory

Solar neutrinos from the decay of $^8$B have been detected at the Sudbury Neutrino Observatory (SNO) via the charged current (CC) reaction on deuterium and by the elastic scattering (ES) of electrons. The CC reaction is sensitive exclusively to nu_e's, while the ES reaction also has a small sensitivity to nu_mu's and nu_tau's. The flux of nu_e's from ^8B decay measured by the CC reaction rate is \phi^CC(nu_e) = 1.75 +/- 0.07 (stat)+0.12/-0.11 (sys.) +/- 0.05(theor) x 10^6 /cm^2 s. Assuming no flavor transformation, the flux inferred from the ES reaction rate is \phi^ES(nu_x) = 2.39+/-0.34 (stat.)+0.16}/-0.14 (sys) x 10^6 /cm^2 s. Comparison of \phi^CC(nu_e) to the Super-Kamiokande Collaboration's precision value of \phi^ES(\nu_x) yields a 3.3 sigma difference, providing evidence that there is a non-electron flavor active neutrino component in the solar flux. The total flux of active ^8B neutrinos is thus determined to be 5.44 +/-0.99 x 10^6/cm^2 s, in close agreement with the predictions of solar models.Comment: 6 pages (LaTex), 3 figures, submitted to Phys. Rev. Letter

A double-sided silicon micro-strip super-module for the ATLAS inner detector upgrade in the high-luminosity LHC

The ATLAS experiment is a general purpose detector aiming to fully exploit the discovery potential of the Large Hadron Collider (LHC) at CERN. It is foreseen that after several years of successful data-taking, the LHC physics programme will be extended in the so-called High-Luminosity LHC, where the instantaneous luminosity will be increased up to 5 × 1034 cm−2 s−1. For ATLAS, an upgrade scenario will imply the complete replacement of its internal tracker, as the existing detector will not provide the required performance due to the cumulated radiation damage and the increase in the detector occupancy. The current baseline layout for the new ATLAS tracker is an all-silicon-based detector, with pixel sensors in the inner layers and silicon micro-strip detectors at intermediate and outer radii. The super-module is an integration concept proposed for the strip region of the future ATLAS tracker, where double-sided stereo silicon micro-strip modules are assembled into a low-mass local support structure. An electrical super-module prototype for eight double-sided strip modules has been constructed. The aim is to exercise the multi-module readout chain and to investigate the noise performance of such a system. In this paper, the main components of the current super-module prototype are described and its electrical performance is presented in detail

Menopausal hormone therapy and other breast cancer risk factors in relation to the risk of different histological subtypes of breast cancer: a case-control study

INTRODUCTION: Breast cancers of different histology have different clinical and prognostic features. There are also indications of differences in aetiology. We therefore evaluated the risk of the three most common histological subtypes in relation to menopausal hormone therapy and other breast cancer risk factors. METHODS: We used a population-based case-control study of breast cancer to evaluate menopausal hormone therapy and other breast cancer risk factors for risk by histological subtype. Women aged 50 to 74 years, diagnosed with invasive ductal (n = 1,888), lobular (n = 308) or tubular (n = 93) breast cancer in Sweden in 1993 to 1995 were compared with 3,065 age-frequency matched controls randomly selected from the population. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for ductal, lobular, and tubular cancer. RESULTS: Women who had used medium potency estrogen alone were at increased risks of both ductal and lobular cancer. Medium potency estrogen-progestin was associated with increased risks for all subtypes, but the estimates for lobular and tubular cancer were higher compared with ductal cancer. We found OR 5.6 (95% CI 3.2–9.7) for lobular cancer, OR 6.5 (95% CI 2.8–14.9) for tubular cancer and OR 2.3 (95% CI 1.6–3.3) for ductal cancer with ≥5 years use of medium potency estrogen-progestin therapy. Low potency oral estrogen (mainly estriol) appeared to be associated with an increased risk for lobular cancer, but the association was strongest for short-term use. Reproductive and anthropometric factors, smoking, and past use of oral contraceptives were mostly similarly related to the risks of the three breast cancer subtypes. Recent alcohol consumption of > 10 g alcohol/day was associated with increased risk only for tubular cancer (OR 3.1, 95% CI 1.4–6.8). CONCLUSION: Menopausal hormone therapy was associated with increased risks for breast cancer of both ductal and lobular subtype, and medium potency estrogen-progestin therapy was more strongly associated with lobular compared with ductal cancer. We also found medium potency estrogen-progestin therapy and alcohol to be strongly associated with tubular cancer. With some exceptions, most other risk factors seemed to be similarly associated with the three subtypes of breast cancer

A double-sided, shield-less stave prototype for the ATLAS upgrade strip tracker for the high luminosity LHC

A detailed description of the integration structures for the barrel region of the silicon strips tracker of the ATLAS Phase-II upgrade for the upgrade of the Large Hadron Collider, the so-called High Luminosity LHC (HL-LHC), is presented. This paper focuses on one of the latest demonstrator prototypes recently assembled, with numerous unique features. It consists of a shortened, shield-less, and double sided stave, with two candidate power distributions implemented. Thermal and electrical performances of the prototype are presented, as well as a description of the assembly procedures and tools

Radiation hardness studies of a 130 nm Silicon Germanium BiCMOS technology with a dedicated ASIC

We present the radiation hardness studies on the bipolar devices of the 130 nm 8WL Silicon Germanium (SiGe) BiCMOS technology from IBM. This technology has been proposed as one of the candidates for the Front-End (FE) readout chip of the upgraded Inner Detector (ID) and the Liquid Argon Calorimeter (LAr) of the ATLAS Upgrade experiment. After neutron irradiations, devices remain at acceptable performances at the maximum radiation levels expected in the Si tracker and LAr calorimeter