bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular diagnostics for congenital hearing loss including 15 deafness genes using a next generation sequencing platform
Authors: De Keulenaer Sarah , Hellemans Jan , Lefever Steve , Renard Jean-Pierre , De Schrijver Joachim , Van de Voorde Hendrik , Tabatabaiefar Mohammad Amin , Van Nieuwerburgh Filip , Flamez Daisy , Pattyn Filip , Scharlaken Bieke , Deforce Dieter , Bekaert Sofie , Van Criekinge Wim , Vandesompele Jo , Van Camp Guy , Coucke Paul 
Published: May 2012

Abstract

Background
Hereditary hearing loss (HL) can originate from mutations in one of many genes involved in the complex process of hearing. Identification of the genetic defects in patients is currently labor intensive and expensive. While screening with Sanger sequencing for GJB2 mutations is common, this is not the case for the other known deafness genes (> 60). Next generation sequencing technology (NGS) has the potential to be much more cost efficient. Published methods mainly use hybridization based target enrichment procedures that are time saving and efficient, but lead to loss in sensitivity. In this study we used a semi-automated PCR amplification and NGS in order to combine high sensitivity, speed and cost efficiency.

Results
In this proof of concept study, we screened 15 autosomal recessive deafness genes in 5 patients with congenital genetic deafness. 646 specific primer pairs for all exons and most of the UTR of the 15 selected genes were designed using primerXL. Using patient specific identifiers, all amplicons were pooled and analyzed using the Roche 454 NGS technology. Three of these patients are members of families in which a region of interest has previously been characterized by linkage studies. In these, we were able to identify two new mutations in CDH23 and OTOF. For another patient, the etiology of deafness was unclear, and no causal mutation was found. In a fifth patient, included as a positive control, we could confirm a known mutation in TMC1.

Conclusions
We have developed an assay that holds great promise as a tool for screening patients with familial autosomal recessive nonsyndromal hearing loss (ARNSHL). For the first time, an efficient, reliable and cost effective genetic test, based on PCR enrichment, for newborns with undiagnosed deafness is available.
Serum amyloid A triggers the mosodium urate -mediated mature interleukin-1β production from human synovial fibroblasts
Authors: Migita Kiyoshi , Koga Tomohiro , Satomura Kenshi , Izumi Masahiro , Torigoshi Takafumi , Maeda Yumi , Izumi Yasumori , Jiuchi Yuka , Miyashita Taiichiro , Yamasaki Satoshi , Aiba Yoshihiro , Komori Atsumasa , Nakamura Minoru , Motokawa Satoru , Kawakami Atsushi , Nakamura Tadashi , Ishibashi Hiromi 
Published: May 2012

Abstract
Background
Monosodium urate (MSU) has been shown to promote inflammasome activation and interleukin-1β (IL-1β) secretion in monocyte/macrophages, but the cellular pathway and nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation in synovial tissues, remain elusive. In this study, we investigated the effects of MSU on synovial fibroblasts to elucidate the process of MSU-mediated synovial inflammation.

Methods
Human synovial fibroblasts were stimulated with MSU in the presence or absence of serum amyloid A (SAA). The cellular supernatants were analyzed by immunoblotting using anti-IL-1β or anti-caspase-1 antibodies. IL-1β or NLRP3 mRNA expressions were analyzed by real-time PCR or reverse transcription-PCR (RT-PCR) method.

Results
Neither SAA nor MSU stimulation resulted in IL-1β or interleukin-1α (IL-1α) secretions and pro-IL-1β processing in synovial fibroblasts. However, in SAA-primed synovial fibroblasts, MSU stimulation resulted in the activation of caspase-1 and production of active IL-1β and IL-1α. The effect of SAA on IL-1β induction was impaired in cells by silencing NLRP3 using siRNA or treating with caspase-1 inhibitor. In addition, SAA induced the secretion of cathepsin B and NLRP3 mRNA expression in synovial fibroblasts.

Conclusions
Our data demonstrate that exposure of human synovial fibroblasts to SAA promotes MSU-mediated caspase-1 activation and IL-1β secretion in the absence of microbial stimulation. These findings provide insight into the molecular processes underlying the synovial inflammatory condition of gout.
Red cell distribution width improves the simplified acute physiology score for risk prediction in unselected critically ill patients
Authors: Hunziker Sabina , Celi Leo A , Lee Joon , Howell Michael D 
Published: May 2012

Abstract
Introduction
Recently, red cell distribution width (RDW), a measure of erythrocyte size variability, has been shown to be a prognostic marker in critical illness. The aim of this study was to investigate whether adding RDW has the potential to improve the prognostic performance of the simplified acute physiology score (SAPS) to predict short- and long-term mortality in an independent, large, and unselected population of intensive care unit (ICU) patients.

Methods
This observational cohort study includes 17,922 ICU patients with available RDW measurements from different types of ICUs. We modeled the association between RDW and mortality by using multivariable logistic regression, adjusting for demographic factors, comorbidities, hematocrit, and severity of illness by using the SAPS.

Results
ICU-, in-hospital-, and 1-year mortality rates in the 17,922 included patients were 7.6% (95% CI, 7.2 to 8.0), 11.2% (95% CI, 10.8 to 11.7), and 25.4% (95% CI, 24.8 to 26.1). RDW was significantly associated with in-hospital mortality (OR per 1% increase in RDW (95%CI)) (1.14 (1.08 to 1.19), P < 0.0001), ICU mortality (1.10 (1.06 to 1.15), P < 0.0001), and 1-year mortality (1.20 (95% CI, 1.14 to 1.26); P < 0.001). Adding RDW to SAPS significantly improved the AUC from 0.746 to 0.774 (P < 0.001) for in-hospital mortality and 0.793 to 0.805 (P < 0.001) for ICU mortality. Significant improvements in classification of SAPS were confirmed in reclassification analyses. Subgroups demonstrated robust results for gender, age categories, SAPS categories, anemia, hematocrit categories, and renal failure.

Conclusions
RDW is a promising independent short- and long-term prognostic marker in ICU patients and significantly improves risk stratification of SAPS. Further research is needed the better to understand the pathophysiology underlying these effects.
Arf6 negatively controls the rapid recycling of the β2AR
Authors: Macia E. , Partisani M. , Paleotti O. , Luton F. , Franco M. 
Published: May 2012

β2-adrenergic receptor (β2AR), a member of the GPCR (G-Proteins Coupled Receptor) family, is internalized in a ligand- and β-arrestin-dependent manner into early endosomes, and subsequently recycled back to the plasma membrane. Here we report that β-arrestin promotes the activation of the small G protein Arf6, which regulates the recycling and degradation of β2AR. We demonstrate in vitro that the C-terminal region of β-arrestin1 interacted directly and simultaneously with Arf6GDP and its specific exchange factor EFA6, to promote Arf6 activation. Similarly, the ligand-mediated activation of β2AR leads to the formation of Arf6GTP in vivo in a β-arrestin-dependent manner. Expression of either EFA6 or an activated Arf6 mutant caused accumulation of β2AR in the degradation pathway. And this phenotype could be rescued by the expression of an activated mutant of Rab4, suggesting that Arf6 acts upstream of Rab4.
We propose a model in which Arf6 plays an essential role for the β2AR desensitization. The ligand-mediated stimulation of β2AR relocates β-arrestin to the plasma membrane, and triggers the activation of Arf6 by EFA6. The activated Arf6 leads to accumulation of β2AR to the degradation pathway, and negatively controls the Rab4-dependent fast recycling to prevent the re-sensitization of β2AR.
Efficient Cost Allocation
Authors: Ray Korok , Goldmanis Maris 
Published: May 2012

Firms routinely allocate the costs of common corporate resources down to divisions. The main insight of this paper is that any efficient allocation rule must reflect the firm's underlying cost structure. We propose a new allocation rule (the polynomial rule), which achieves efficiency and approximate budget balance. Welfare losses due to linear allocation rules increase with firm size, so polynomial allocation rules dominate linear rules for larger firms. This paper was accepted by Mary E. Barth, accounting.
Measuring the Informative and Persuasive Roles of Detailing on Prescribing Decisions
Authors: Ching Andrew T. , Ishihara Masakazu 
Published: May 2012

In the pharmaceutical industry, measuring the importance of informative and persuasive roles of detailing is crucial for both drug manufacturers and policy makers. However, little progress has been made in disentangling these two roles of detailing in empirical research. In this paper, we provide a new identification strategy to address this problem. Our key identification assumptions are that the informative component of detailing is chemical specific and the persuasive component is brand specific. Our strategy is to focus on markets where some drug manufacturers engage in a comarketing agreement, under which two or more companies market the same chemical using their own brand names. With our identification assumptions, the variation in the relative market shares of these two brands, together with their brand specific detailing efforts, would allow us to measure the persuasive component of detailing. The variation in the market shares of chemicals, and the detailing efforts summed across brands made of the same chemical, would allow us to measure the informative component of detailing. Using the data for angiotensin-converting enzyme inhibitor with diuretic in Canada, we find evidence that our identification strategy can help disentangle these two effects. Although both effects are statistically significant, we find that the persuasive function of detailing plays a very minor role in determining the demand at the chemical level—the informative role of detailing is mainly responsible for the diffusion patterns of chemicals. In contrast, the persuasive role of detailing plays a crucial role in determining the demand for brands that comarket the same chemical. This paper was accepted by Pradeep Chintagunta, marketing.
A Generalized Norton–Bass Model for Multigeneration Diffusion
Authors: Jiang Zhengrui , Jain Dipak C. 
Published: May 2012

The Norton–Bass (NB) model is often credited as the pioneering multigeneration diffusion model in marketing. However, as acknowledged by the authors, when counting the number of adopters who substitute an old product generation with a new generation, the NB model does not differentiate those who have already adopted the old generation from those who have not. In this study, we develop a generalized Norton–Bass (GNB) model that separates the two different types of substitutions. The GNB model provides closed-form expressions for both the number of units in use and the adoption rate, and offers greater flexibility in parameter estimation, forecasting, and revenue projection. An appealing aspect of the GNB model is that it uses exactly the same set of parameters as the NB model and is mathematically consistent with the later. Empirical results show that the GNB model delivers better overall performance than previous models both in terms of model fit and forecasting performance. The analyses also show that differentiating leapfrogging and switching adoptions based on the GNB model can help gain additional insights into the process of multigeneration diffusion. Furthermore, we demonstrate that the GNB model can incorporate the effect of marketing mix variables on the speed of diffusion for all product generations. This paper was accepted by Pradeep Chintagunta, marketing.
Analysis of Gamma-Ray Dosimetry Experiments in the Zero Power MINERVE Facility
Authors: Amharrak H. , Di Salvo J. , Lyoussi A. , Roche A. , Masson-Fauchier M. , Bosq J. C. , Carette M. 
Published: May 2012

Abstract
The objective of this study is to develop nuclear heating measurement methods in zero power experimental reactors. These developments contribute to the qualification of photonics calculation schemes for the assessment of gamma heating in the future Jules Horowitz Material Testing Reactor. This paper presents the analysis of thermoluminescent detector (TLD) experiments in the UO2 core of the MINERVE Research Reactor at the French Alternative Energies and Atomic Energy Commission center in Cadarache. The experimental sources of uncertainty in the gamma dose have been reduced by improving the measurement conditions and the repeatability of the calibration step for each individual TLD. The interpretation of these measurements needs to take into account the calculation of cavity correction factors related to calibration and irradiation configurations, as well as neutron correction calculations. These calculations are based on Monte Carlo simulations of neutron-gamma and gamma-electron transport coupled particles. The comparison between calculated and measured integral gamma-ray absorbed doses in the aluminum material surrounding the TLD shows that calculations slightly overestimate the measurement, with a calculated versus experimental ratio equal to 1.04 ± 5.7 % (k = 2).
Uncertainty-Accounted Calculational–Experimental Approach for Improved Conservative Evaluations of VVER RPV Radiation Loading Parameters
Authors: Borodkin P. G. , Borodkin G. I. , Khrennikov N. N. 
Published: May 2012

Abstract
The approach of improved uncertainty-accounted conservative evaluation of vodo-vodyanoi energetichesky reactor (VVER) (reactor-) pressure-vessel (RPV) radiation loading parameters has been proposed. This approach is based on the calculational–experimental procedure, which takes into account C/E ratio, depending on over- or underestimation, and uncertainties of measured and calculated results. An application of elaborated approach to the full-scale ex-vessel neutron dosimetry experiments on Russian VVERs combined with neutron-transport calculations has been demonstrated in the paper.
New Measurements and the Associated Unfolding Methodologies to Characterize the Caliban Pulsed Reactor Cavity Neutron Spectrum by the Foil Activation Method
Authors: Jacquet X. , Casoli P. , Authier N. , Rousseau G. , Barsu C. 
Published: May 2012

Abstract
Caliban is a cylindrical metallic core reactor mainly composed of uranium 235. It is operated by the Criticality and Neutron Science Research Laboratory located at the French Atomic Energy Commission research center in Valduc. As with other fast burst reactors, Caliban is used extensively for determining the responses of electronic parts or other objects and materials to neutron-induced displacements. Therefore, Caliban’s irradiation characteristics, and especially its central cavity neutron spectrum, have to be very accurately evaluated. The foil activation method has been used in the past by the Criticality and Neutron Science Research Laboratory to evaluate the neutron spectrum of the different facilities it operated, and in particular to characterize the Caliban cavity spectrum. In order to strengthen and to improve our knowledge of the Caliban cavity neutron spectrum and to reduce the uncertainties associated with the available evaluations, new measurements have been performed on the reactor and interpreted by the foil activation method. A sensor set has been selected to sample adequately the studied spectrum. Experimental measured reaction rates have been compared to the results from UMG spectrum unfolding software and to values obtained with the activation code Fispact. Experimental and simulation results are overall in good agreement, although gaps exist for some sensors. UMG software has also been used to rebuild the Caliban cavity neutron spectrum from activation measurements. For this purpose, a default spectrum is needed, and one has been calculated with the Monte-Carlo transport code Tripoli 4 using the benchmarked Caliban description.
A Feasibility Study to Determine Cooling Time and Burnup of Advanced Test Reactor Fuel Using a Nondestructive Technique and Three Types of Gamma-ray Detectors
Authors: Navarro J. , Aryaeinejad R. , Nigg D. W. 
Published: May 2012

Abstract
The goal of this work was to perform a feasibility study and establish measurement techniques to determine the burnup of the Advanced Test Reactor (ATR) fuels at the Idaho National Laboratory (INL). Three different detectors of high purity germanium (HPGe), lanthanum bromide (LaBr3), and high pressure xenon (HPXe) in two detection system configurations of below and above the water pool were used in this study. The last two detectors were used for the first time in fuel burnup measurements. The results showed that a better quality spectra can be achieved with the above the water pool configuration. Both short and long cooling time fuels were investigated in order to determine which measurement technique, absolute or fission product ratio, is better suited in each scenario and also to establish what type of detector should be used in each case for the best burnup measurement. The burnup and cooling time calibrations were established using experimental absolute activities or isotopic ratios and ORIGEN burnup calculations. A method was developed to do burnup and cooling time calibrations using fission isotopes activities without the need to know the exact geometry.
Neutron Flux Measurements in the Side-Core Region of Hunterston B Advanced Gas-Cooled Reactor
Authors: Allen D. A. , Shaw S. E. , Huggon A. P. , Steadman R. J. , Thornton D. A. , Whiley G. S. 
Published: May 2012

Abstract
The core restraints of advanced gas-cooled reactors are important structural components that are required to maintain the geometric integrity of the cores. A review of neutron dosimetry for the sister stations Hunterston B and Hinkley Point B identified that earlier conservative assessments predicted high thermal neutron dose rates to key components of the restraint structure (the restraint rod welds), with the implication that some of them may be predicted to fail during a seismic event. A revised assessment was therefore undertaken [Thornton, D. A., Allen, D. A., Tyrrell, R. J., Meese, T. C., Huggon, A.P., Whiley, G. S., and Mossop, J. R., “A Dosimetry Assessment for the Core Restraint of an Advanced Gas Cooled Reactor,” Proceedings of the 13th International Symposium on Reactor Dosimetry (ISRD-13, May 2008), World Scientific, River Edge, NJ, 2009, W. Voorbraak, L. Debarberis, and P. D’hondt, Eds., pp. 679–687] using a detailed 3D model and a Monte Carlo radiation transport program, mcbend. This reassessment resulted in more realistic fast and thermal neutron dose recommendations, the latter in particular being much lower than had been thought previously. It is now desirable to improve confidence in these predictions by providing direct validation of the mcbend model through the use of neutron flux measurements. This paper describes the programme of work being undertaken to deploy two neutron flux measurement “stringers” within the side-core region of one of the Hunterston B reactors for the purpose of validating the mcbend model. The design of the stringers and the determination of the preferred deployment locations have been informed by the use of detailed mcbend flux calculations. These computational studies represent a rare opportunity to design a flux measurement beforehand, with the clear intention of minimising the anticipated uncertainties and obtaining measurements that are known to be representative of the neutron fields to which the vulnerable steel restraint components are exposed.
Structure Transformations in Multicomponent Amorphous Alloys in Connection with Grain-Boundary Segregations and Temper Embrittlement of Steels
Authors: Lyasotsky I. V. , Dyakonova N. B. , Dyakonov D. L. 
Published: May 2012

Abstract
Investigation of glass-forming alloys on the base of Fe–P system with additions of C, Mn, Cr, Si, and Ni with compositions modeling segregations on grain boundaries in steels revealed the existence of a metastable phase that precipitates at the initial stages of devitrification. This crystalline tetrahedrally close-packed phase of α–Mn structure type (χ-phase) and its aperiodic modification (cubic quasicrystal) contain less phosphorus than the known stable and metastable phosphides. Positions of P and C atoms in the unit cell of the χ-phase lattice have been established. The necessary condition for precipitation of the quasicrystalline phase is the presence of carbon. Additions of Mn + Si, Mn, or Cr promote both formation of the χ-phase and formation of the quasicrystal, their influence decreasing in this order. Composition dependences of liability to formation of the quasicrystalline structures in the model alloys agree with the data on the impact of alloying elements on the temper embrittlement of steels.
A New Technique for Dosimetry Reaction Cross-Section Evaluation
Authors: Badikov S. A. 
Published: May 2012

Abstract
An objective of this paper is a unification of the procedure for dosimetry reaction cross-section evaluation. A set of requirements for the unified evaluation procedure is presented. A new code (ORTHO) was developed in order to meet these requirements. A statistical model, an algorithm, and the basic formulae employed in the code are described. The code was used for Ti48(n,p) reaction cross-section evaluation. The results of the evaluation are compared to International Reactor Dosimetry File (IRDF)-2002 data. The evaluated cross-sections and their correlations from this work are in good agreement with the IRDF-2002 evaluated data, whereas the uncertainties of the evaluated cross-sections are inconsistent.
Benchmarking of Neutron Production of Heavy-Ion Transport Codes
Authors: Remec I. , Ronningen R. M. , Heilbronn L. 
Published: May 2012

Abstract
Accurate prediction of radiation fields generated by heavy ion interactions is important in medical applications, space missions, and in design and operation of rare isotope research facilities. In recent years, several well-established computer codes in widespread use for particle and radiation transport calculations have been equipped with the capability to simulate heavy ion transport and interactions. To assess and validate these capabilities, we performed simulations of a series of benchmark-quality heavy ion experiments with the computer codes FLUKA, MARS15, MCNPX, and PHITS. We focus on the comparisons of secondary neutron production. Results are encouraging; however, further improvements in models and codes and additional benchmarking are required.