bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel proteasome inhibitor suppresses tumor growth via targeting both 19S proteasome deubiquitinases and 20S proteolytic peptidases
Authors: Liu Ningning , Liu Chunjiao , Li Xiaofen , Liao Siyan , Song Wenbin , Yang Changshan , Zhao Chong , Huang Hongbiao , Guan Lixia , Zhang Peiquan , Liu Shouting , Hua Xianliang , Chen Xin , Zhou Ping , Lan Xiaoying , Yi Songgang , Wang Shunqing , Wang Xuejun , Dou Q. Ping , Liu Jinbao 
Published: June 2014

AbstractThe successful development of bortezomib-based therapy for treatment of multiple myeloma has established proteasome inhibition as an effective therapeutic strategy and both 20S proteasome peptidases and 19S deubiquitinases (DUBs) are becoming attractive targets of cancer therapy. It has been reported that metal complexes, such as copper complexes, inhibit tumor proteasome. However, the involved mechanism of action has not been fully characterized. Here we report that (i) copper pyrithione (CuPT), an alternative to tributyltin for antifouling paint biocides, inhibits the ubiquitin-proteasome system (UPS) via targeting both 19S proteasome-specific DUBs and 20S proteolytic peptidases with a mechanism distinct from that of the FDA-approved proteasome inhibitor bortezomib; (ii) CuPT potently inhibits proteasome-specific UCHL5 and USP14 activities; (iii) CuPT inhibits tumor growth in vivo and induces cytotoxicity in vitro and ex vivo. This study uncovers a novel class of dual inhibitors of DUBs and proteasome and suggests a potential clinical strategy for cancer therapy.
Identification of protein succination as a novel modification of tubulin
Authors: Piroli Gerardo G. , Manuel Allison M. , Walla Michael D. , Jepson Matthew J. , Brock Jonathan W. C. , Rajesh Mathur P. , Tanis Ross M. , Cotham William E. , Frizzell Norma 
Published: June 2014

Protein succination is a stable post-translational modification that occurs when fumarate reacts with cysteine residues to generate 2SC [S-(2-succino)cysteine]. We demonstrate that both α- and β-tubulin are increasingly modified by succination in 3T3-L1 adipocytes and in the adipose tissue of db/db mice. Incubation of purified tubulin from porcine brain with fumarate (50 mM) or the pharmacological compound DMF (dimethylfumarate, 500 μM) inhibited polymerization up to 35% and 59% respectively. Using MS we identified Cys347α, Cys376α, Cys12β and Cys303β as sites of succination in porcine brain tubulin and the relative abundance of succination at these cysteine residues increased in association with fumarate concentration. The increase in succination after incubation with fumarate altered tubulin recognition by an anti-α-tubulin antibody. Succinated tubulin in adipocytes cultured in high glucose compared with normal glucose also had reduced reactivity with the anti-α-tubulin antibody; suggesting that succination may interfere with tubulin–protein interactions. DMF reacted rapidly with 11 of the 20 cysteine residues in the αβ-tubulin dimer, decreased the number of free thiols and inhibited the proliferation of 3T3-L1 fibroblasts. Our data suggest that inhibition of tubulin polymerization is an important undocumented mechanism of action of DMF. Taken together, our results demonstrate that succination is a novel post-translational modification of tubulin and suggest that extensive modification by fumarate, either physiologically or pharmacologically, may alter microtubule dynamics.
European Clinical Specialization in Fluency Disorders (ECSF): Participants Review the First Four Years
Authors: Leahy Margaret , Agius Joseph , Hylebos Carl , De Nil Luc , Eggers Kurt 
Published: June 2014

Background: The European Clinical Specialization in Fluency Disorders (ECSF) is a 1-year postgraduate course for speech and language therapists (known as speech-language pathologists in the United States). The program was developed by a consortium whose members are specialists in fluency disorders from European universities/colleges. The consortium expanded to include other EU college members and specialists from EU centers of clinical excellence.
Purpose: This paper presents an evaluative review by students and teachers who have participated in the initial 4 years of ECSF courses.
Methodology: Two mixed methods online survey questionnaire were used, one for each group (student course participants and consortium members, designated as teachers throughout the paper) with quantitative, comparative data gathering, along with elements of qualitative data emerging from invited comments, and from open-ended questions.
Results: High and relatively high levels of satisfaction were expressed by all participants regarding the overall experience of ECSF. There was a wider range of satisfaction expressed by student participants regarding aspects of course content and experience of clinical work. Participants' responses providing qualitative data indicate major influences of the ECSF on professional development, and strong appreciation of participation in ECSF.
NOKIN1D: one-dimensional neutron kinetics based on a nodal collocation method
Authors: Verdú G. , Ginestar D. , Miró R. , Jambrina A. , Barrachina T. , Soler Amparo , Concejal Alberto 
Published: June 2014

The TRAC-BF1 one-dimensional kinetic model is a formulation of the neutron diffusion equation in the two energy groups’ approximation, based on the analytical nodal method (ANM). The advantage compared with a zero-dimensional kinetic model is that the axial power profile may vary with time due to thermal-hydraulic parameter changes and/or actions of the control systems but at has the disadvantages that in unusual situations it fails to converge.
The nodal collocation method developed for the neutron diffusion equation and applied to the kinetics resolution of TRAC-BF1 thermal-hydraulics, is an adaptation of the traditional collocation methods for the discretization of partial differential equations, based on the development of the solution as a linear combination of analytical functions. It has chosen to use a nodal collocation method based on a development of Legendre polynomials of neutron fluxes in each cell.
The qualification is carried out by the analysis of the turbine trip transient from the NEA benchmark in Peach Bottom NPP using both the original 1D kinetics implemented in TRAC-BF1 and the 1D nodal collocation method.
Coupled Neutron Transport and Thermal Fluids Calculations for the VHTR
Authors: John Connolly Kevin , Huning Alexander J. , Rahnema Farzad , Garimella Srinivas 
Published: June 2014

A new multiphysics method is presented for coupled neutronics and thermal fluids calculations in the VHTR. This new method combines the capabilities of two existing solvers: the COMET neutronics solver, and a thermal fluids module designed specifically for the gas-cooled reactor lattice design featured in this next-generation reactor. This paper provides the necessary background on the neutronics and thermal fluids aspects of the new solution strategy and explains the mode of coupling. A test problem is presented in order to prove the efficacy of the new coupled method.
Results are given for a whole-core VHTR, including detailed temperature information at the fuel pin level, explicit power calculations of individual pins, and a thermal map of the bulk graphite and coolant temperatures throughout the core. Solutions are determined quickly when compared to other methods which offer the same level of detail and accuracy, and thus justify further research and development of this method in the near future.
CAD-based Automatic Modeling Method for Geant4 geometry model Through MCAM
Authors: Wang Dong , Nie Fanzhi , Wang Guozhong , Long Pengcheng , LV Zhongliang , LV Zhongliang ,   FDS Team
Published: June 2014

Geant4 is a widely used Monte Carlo transport simulation package. Before calculating using Geant4, the calculation model need be established which could be described by using Geometry Description Markup Language (GDML) or C++ language. However, it is time-consuming and error-prone to manually describe the models by GDML. Automatic modeling methods have been developed recently, but there are some problem existed in most of present modeling programs, specially some of them were not accurate or adapted to specifically CAD format. To convert the GDML format models to CAD format accurately, a Geant4 Computer Aided Design (CAD) based modeling method was developed for automatically converting complex CAD geometry model into GDML geometry model.
The essence of this method was dealing with CAD model represented with boundary representation (B-REP) and GDML model represented with constructive solid geometry (CSG). At first, CAD model was decomposed to several simple solids which had only one close shell. And then the simple solid was decomposed to convex shell set. Then corresponding GDML convex basic solids were generated by the boundary surfaces getting from the topological characteristic of a convex shell. After the generation of these solids, GDML model was accomplished with series boolean operations.
This method was adopted in CAD/Image-based Automatic Modeling Program for Neutronics & Radiation Transport (MCAM), and tested with several models including the examples in Geant4 install package. The results showed that this method could convert standard CAD model accurately, and can be used for Geant4 automatic modeling.
Extensions of the MCNP5 and TRIPOLI4 Monte Carlo Codes for Transient Reactor Analysis
Authors: Eduard Hoogenboom J. , Sjenitzer Bart L. 
Published: June 2014

To simulate reactor transients for safety analysis with the Monte Carlo method the generation and decay of delayed neutron precursors is implemented in the MCNP5 and TRIPOLI4 general purpose Monte Carlo codes. Important new variance reduction techniques like forced decay of precursors in each time interval and the branchless collision method are included to obtain reasonable statistics for the power production per time interval.
For simulation of practical reactor transients also the feedback effect from the thermal-hydraulics must be included. This requires coupling of the Monte Carlo code with a thermal-hydraulics (TH) code, providing the temperature distribution in the reactor, which affects the neutron transport via the cross section data. The TH code also provides the coolant density distribution in the reactor, directly influencing the neutron transport. Different techniques for this coupling are discussed.
As a demonstration a 3x3 mini fuel assembly with a moving control rod is considered for MCNP5 and a mini core existing of 3x3 PWR fuel assemblies with control rods and burnable poisons for TRIPOLI4. Results are shown for reactor transients due to control rod movement or withdrawal. The TRIPOLI4 transient calculation is started at low power and includes thermal-hydraulic feedback. The power rises about 10 decades and finally stabilises the reactor power at a much higher level than initial. The examples demonstrate that the modified Monte Carlo codes are capable of performing correct transient calculations, taking into account all geometrical and cross section detail.
Present Status and Extensions of the Monte Carlo Performance Benchmark
Authors: Eduard Hoogenboom J. , Petrovic Bojan , Martin William R. 
Published: June 2014

The NEA Monte Carlo Performance benchmark started in 2011 aiming to monitor over the years the abilities to perform a full-size Monte Carlo reactor core calculation with a detailed power production for each fuel pin with axial distribution. This paper gives an overview of the contributed results thus far. It shows that reaching a statistical accuracy of 1 % for most of the small fuel zones requires about 100 billion neutron histories. The efficiency of parallel execution of Monte Carlo codes on a large number of processor cores shows clear limitations for computer clusters with common type computer nodes. However, using true supercomputers the speedup of parallel calculations is increasing up to large numbers of processor cores. More experience is needed from calculations on true supercomputers using large numbers of processors in order to predict if the requested calculations can be done in a short time.
As the specifications of the reactor geometry for this benchmark test are well suited for further investigations of full-core Monte Carlo calculations and a need is felt for testing other issues than its computational performance, proposals are presented for extending the benchmark to a suite of benchmark problems for evaluating fission source convergence for a system with a high dominance ratio, for coupling with thermal-hydraulics calculations to evaluate the use of different temperatures and coolant densities and to study the correctness and effectiveness of burnup calculations. Moreover, other contemporary proposals for a full-core calculation with realistic geometry and material composition will be discussed.
Hybrid parallel strategy for the simulation of fast transient accidental situations at reactor scale
Authors: Faucher V. , Galon P. , Beccantini A. , Crouzet F. , Debaud F. , Gautier T. 
Published: June 2014

This contribution is dedicated to the latest methodological developments implemented in the fast transient dynamics software EUROPLEXUS (EPX) to simulate the mechanical response of fully coupled fluid-structure systems to accidental situations to be considered at reactor scale, among which the Loss of Coolant Accident, the Core Disruptive Accident and the Hydrogen Explosion.
Time integration is explicit and the search for reference solutions within the safety framework prevents any simplification and approximations in the coupled algorithm: for instance, all kinematic constraints are dealt with using Lagrange Multipliers, yielding a complex flow chart when non-permanent constraints such as unilateral contact or immersed fluid-structure boundaries are considered. The parallel acceleration of the solution process is then achieved through a hybrid approach, based on a weighted domain decomposition for distributed memory computing and the use of the KAAPI library for self-balanced shared memory processing inside subdomains.
Image based Monte Carlo Modeling for Computational Phantom
Authors: Cheng Mengyun , Wang Wen , Zhao Kai , Fan Yanchang , Long Pengcheng , Wu Yican ,   FDS Team
Published: June 2014

The evaluation on the effects of ionizing radiation and the risk of radiation exposure on human body has been becoming one of the most important issues for radiation protection and radiotherapy fields, which is helpful to avoid unnecessary radiation and decrease harm to human body. In order to accurately evaluate the dose on human body, it is necessary to construct more realistic computational phantom. However, manual description and verfication of the models for Monte carlo(MC)simulation are very tedious, error-prone and time-consuming. In addiation, it is difficult to locate and fix the geometry error, and difficult to describe material information and assign it to cells.
MCAM (CAD/Image-based Automatic Modeling Program for Neutronics and Radiation Transport Simulation) was developed as an interface program to achieve both CAD- and image-based automatic modeling by FDS Team (Advanced Nuclear Energy Research Team, http://www.fds.org.cn). The advanced version (Version 6) of MCAM can achieve automatic conversion from CT/segmented sectioned images to computational phantoms such as MCNP models.
Imaged-based automatic modeling program(MCAM6.0) has been tested by several medical images and sectioned images. And it has been applied in the construction of Rad-HUMAN. Following manual segmentation and 3D reconstruction, a whole-body computational phantom of Chinese adult female called Rad-HUMAN was created by using MCAM6.0 from sectioned images of a Chinese visible human dataset. Rad-HUMAN contains 46 organs/tissues, which faithfully represented the average anatomical characteristics of the Chinese female. The dose conversion coefficients(Dt/Ka) from kerma free-in-air to absorbed dose of Rad-HUMAN were calculated. Rad-HUMAN can be applied to predict and evaluate dose distributions in the Treatment Plan System (TPS), as well as radiation exposure for human body in radiation protection.
Integration of bacterial lytic polysaccharide monooxygenases into designer cellulosomes promotes enhanced cellulose degradation
Authors: Arfi Yonathan , Shamshoum Melina , Rogachev Ilana , Peleg Yoav , Bayer Edward A. 
Published: June 2014

Significance
Degradation of cellulosic biomass is a key bottleneck in the development of plant-based bioenergies. Studies of cellulolytic microorganisms led to the characterization of a large range of enzymatic systems usable for cellulose breakdown, but current technologies are not efficient enough to warrant their large-scale implementation. This study aims at combining two paradigms in a single system, using a synthetic biology approach. Polysaccharide monooxygenases (redox enzymes capable of boosting cellulose degradation) were engineered to gain the ability to assemble in cellulosomal complexes. As a result of their integration in complexes, these enzymes were able to degrade cellulose at a significantly higher rate compared with the free enzymes, suggesting that this strategy could lead to more efficient technologies for lignocellulose conversion.
Differential expression of APE1 and APE2 in germinal centers promotes error-prone repair and A:T mutations during somatic hypermutation
Authors: Stavnezer Janet , Linehan Erin K. , Thompson Mikayla R. , Habboub Ghaith , Ucher Anna J. , Kadungure Tatenda , Tsuchimoto Daisuke , Nakabeppu Yusaku , Schrader Carol E. 
Published: June 2014

Significance
Error-prone DNA repair of activation-induced cytidine deaminase (AID)-induced lesions in B cells is known to cause hypermutation of the antibody genes and, when coupled with selection mechanisms in germinal centers, leads to increased affinity of antibody. These lesions can also lead to substantial genomic instability that can promote lymphomagenesis, and the cause of error-prone repair is unknown. We have found that expression of an essential DNA repair protein, AP endonuclease (APE) 1, is dramatically reduced in mouse germinal center B cells where somatic hypermutation occurs. By contrast, the very inefficient homologue, APE2, becomes highly expressed. We show that APE2 promotes mutations and present a model proposing that differential expression of APE homologues in germinal centers is a major reason for error-prone repair of AID-induced lesions.
Vesiculoviral matrix (M) protein occupies nucleic acid binding site at nucleoporin pair (Rae1•Nup98)
Authors: Quan Beili , Seo Hyuk-Soo , Blobel Günter , Ren Yi 
Published: June 2014

Significance
Using crystallographic and biochemical studies, we explored how a viral protein, the matrix (M) protein of vesicular stomatitis virus (VSV), affects a pair of cellular proteins: mRNA export factor 1 (Rae1) and nucleoporin Nup98. We identified Rae1 as a nucleic acid-binding protein and showed that the viral M protein mimics the phosphate backbone of any nucleic acid. This mimicry enables VSV M protein to occupy the nucleic acid binding site of Rae1. Because this site is also used as a temporary stopover by host cell mRNA on its passage through the nuclear pore, the viral M protein sabotages host cell mRNA export, thereby paving the way for exclusively cytoplasm-synthesized VSV mRNAs to take over the cell’s protein biosynthesis machineries.
Examining Rowe and Kahn’s Concept of Successful Aging: Importance of Taking a Life Course Perspective
Authors: Stowe James D. , Cooney Teresa M. 
Published: June 2014

Purpose of the Study:
This article critiques Rowe and Kahn’s conceptualization of successful aging using tenets of the life course perspective.

Design and Methods:
A review and synthesis of the literature on successful aging and studies that use a life course perspective.

Results:
We draw on life course principles that view development as a dynamic lifelong process, embedded in historical time and place, and influenced by the web of relationships individuals are linked to, as well as more distal social structural factors. This discussion questions the relatively static nature of Rowe and Kahn’s successful aging model, its emphasis on personal control over one’s later-life outcomes, and neglect of historical and cultural context, social relationships, and structural forces in influencing later-life functioning.

Implications:
Caution in using the model in its current formulation is needed, and we promote thinking about how successful aging can better align with micro- and macrolevel issues through utilization of a life course perspective.
Horizontal distributions of Dungeness crab (Cancer magister) and red rock crab (Cancer productus) larvae in the Strait of Georgia, British Columbia
Authors: Sorochan Kevin A. , Quijón Pedro A. 
Published: June 2014

AbstractThe supply of planktonic larvae to adult populations is an important contributor to the spatial and temporal variability of benthic marine organisms. The ability to predict spatial patterns of larvae and recruits from the physical and biological processes that facilitate dispersal is required in order to advise and evaluate conservation and fisheries management decisions. In the present study, the horizontal distribution of Dungeness crab (Cancer magister) and red rock crab (Cancer productus) zoeae was described from surveys conducted in the Strait of Georgia in the spring of 2009 and 2010. Processes that may be responsible for generating spatial variability of larvae were evaluated based on (i) horizontal overlap between larvae and water properties, (ii) spatial dependence of larvae and water properties, and (iii) changes in the dispersion of stage-specific distributions. Interspecific variability between horizontal patterns of the first and second larval stages was primarily attributed to differences in the distribution of larval release locations, which appeared to be restricted to the southern and central strait for C. magister. Potential effects of physical processes on larval distributions are also discussed.
A topology of Twitter research: disciplines, methods, and ethics
Authors: Zimmer Michael , Proferes Nicholas John 
Published: June 2014

Purpose
– The purpose of this paper is to engage in a systematic analysis of academic research that relies on the collection and use of Twitter data, creating topology of Twitter research that details the disciplines and methods of analysis, amount of tweets and users under analysis, the methods used to collect Twitter data, and accounts of ethical considerations related to these projects.

Design/methodology/approach
– Content analysis of 382 academic publications from 2006 to 2012 that used Twitter as their primary platform for data collection and analysis.

Findings
– The analysis of over 380 scholarly publications utilizing Twitter data reveals noteworthy trends related to the growth of Twitter-based research overall, the disciplines engaged in such research, the methods of acquiring Twitter data for analysis, and emerging ethical considerations of such research.

Research limitations/implications
– The findings provide a benchmark analysis that must be updated with the continued growth of Twitter-based research.

Originality/value
– The research is the first full-text systematic analysis of Twitter-based research projects, focussing on the growth in discipline and methods as well as its ethical implications. It is of value for the broader research community currently engaged in social media-based research, and will prompt reflexive evaluation of what research is occurring, how it is occurring, what is being done with Twitter data, and how researchers are addressing the ethics of Twitter-based research.