Simulation of Light Antinucleus-Nucleus Interactions

Creations of light anti-nuclei (anti-deuterium, anti-tritium, anti-He3 and anti-He4) are observed by collaborations at the LHC and RHIC accelerators. Some cosmic ray experiments are aimed to find the anti-nuclei in cosmic rays. To support the experimental studies of the anti-nuclei a Monte Carlo simulation of anti-nuclei interactions with matter is implemented in the Geant4 toolkit. The implementation combines practically all known theoretical approaches to the problem of antinucleon-nucleon interactions.Comment: 8 pages, 5 figure

Unraveling the Pharmacokinetic Interaction of Ticagrelor and MEDI2452 (Ticagrelor Antidote) by Mathematical Modeling

The investigational ticagrelor-neutralizing antibody fragment, MEDI2452, is developed to rapidly and specifically reverse the antiplatelet effects of ticagrelor. However, the dynamic interaction of ticagrelor, the ticagrelor active metabolite (TAM), and MEDI2452, makes pharmacokinetic (PK) analysis nontrivial and mathematical modeling becomes essential to unravel the complex behavior of this system. We propose a mechanistic PK model, including a special observation model for post-sampling equilibration, which is validated and refined using mouse in vivo data from four studies of combined ticagrelor-MEDI2452 treatment. Model predictions of free ticagrelor and TAM plasma concentrations are subsequently used to drive a pharmacodynamic (PD) model that successfully describes platelet aggregation data. Furthermore, the model indicates that MEDI2452-bound ticagrelor is primarily eliminated together with MEDI2452 in the kidneys, and not recycled to the plasma, thereby providing a possible scenario for the extrapolation to humans. We anticipate the modeling work to improve PK and PD understanding, experimental design, and translational confidence

Parton cascade description of relativistic heavy-ion collisions at CERN SPS energies ?

We examine Pb+Pb collisions at CERN SPS energy 158 A GeV, by employing the earlier developed and recently refined parton-cascade/cluster-hadronization model and its Monte Carlo implementation. This space-time model involves the dynamical interplay of perturbative QCD parton production and evolution, with non-perturbative parton-cluster formation and hadron production through cluster decays. Using computer simulations, we are able to follow the entwined time-evolution of parton and hadron degrees of freedom in both position and momentum space, from the instant of nuclear overlap to the final yield of particles. We present and discuss results for the multiplicity distributions, which agree well with the measured data from the CERN SPS, including those for K mesons. The transverse momentum distributions of the produced hadrons are also found to be in good agreement with the preliminary data measured by the NA49 and the WA98 collaboration for the collision of lead nuclei at the CERN SPS. The analysis of the time evolution of transverse energy deposited in the collision zone and the energy density suggests an existence of partonic matter for a time of more than 5 fm.Comment: 16 pages including 7 postscript figure

Evaluation of rate law approximations in bottom-up kinetic models of metabolism.

BackgroundThe mechanistic description of enzyme kinetics in a dynamic model of metabolism requires specifying the numerical values of a large number of kinetic parameters. The parameterization challenge is often addressed through the use of simplifying approximations to form reaction rate laws with reduced numbers of parameters. Whether such simplified models can reproduce dynamic characteristics of the full system is an important question.ResultsIn this work, we compared the local transient response properties of dynamic models constructed using rate laws with varying levels of approximation. These approximate rate laws were: 1) a Michaelis-Menten rate law with measured enzyme parameters, 2) a Michaelis-Menten rate law with approximated parameters, using the convenience kinetics convention, 3) a thermodynamic rate law resulting from a metabolite saturation assumption, and 4) a pure chemical reaction mass action rate law that removes the role of the enzyme from the reaction kinetics. We utilized in vivo data for the human red blood cell to compare the effect of rate law choices against the backdrop of physiological flux and concentration differences. We found that the Michaelis-Menten rate law with measured enzyme parameters yields an excellent approximation of the full system dynamics, while other assumptions cause greater discrepancies in system dynamic behavior. However, iteratively replacing mechanistic rate laws with approximations resulted in a model that retains a high correlation with the true model behavior. Investigating this consistency, we determined that the order of magnitude differences among fluxes and concentrations in the network were greatly influential on the network dynamics. We further identified reaction features such as thermodynamic reversibility, high substrate concentration, and lack of allosteric regulation, which make certain reactions more suitable for rate law approximations.ConclusionsOverall, our work generally supports the use of approximate rate laws when building large scale kinetic models, due to the key role that physiologically meaningful flux and concentration ranges play in determining network dynamics. However, we also showed that detailed mechanistic models show a clear benefit in prediction accuracy when data is available. The work here should help to provide guidance to future kinetic modeling efforts on the choice of rate law and parameterization approaches

Relativistic Heavy--Ion Collisions in the Dynamical String--Parton Model

We develop and extend the dynamical string parton model. This model, which is based on the salient features of QCD, uses classical Nambu-Got\=o strings with the endpoints identified as partons, an invariant string breaking model of the hadronization process, and interactions described as quark-quark interactions. In this work, the original model is extended to include a phenomenological quantization of the mass of the strings, an analytical technique for treating the incident nucleons as a distribution of string configurations determined by the experimentally measured structure function, the inclusion of the gluonic content of the nucleon through the introduction of purely gluonic strings, and the use of a hard parton-parton interaction taken from perturbative QCD combined with a phenomenological soft interaction. The limited number of parameters in the model are adjusted to $e^+e^-$ and $p$--$p$ data. Utilizing these parameters, the first calculations of the model for $p$--$A$ and $A$--$A$ collisions are presented and found to be in reasonable agreement with a broad set of data.Comment: 26 pages of text with 23 Postscript figures placed in tex

The Adoption and Use of Electronic Information Resources by a Non-Traditional User Group: Automotive Service Technicians.

The growing complexity of machines has led to a concomitant increase in the amount and complexity of the information needed by those charged with servicing them. This, in turn, has led to a need for more robust methods for storing and distributing information and for a workforce more sophisticated in its use of information resources. As a result, the service trades have "professionalized," adopting more rigorous academic standards and developing ongoing certification programs. The current paper deals with the acceptance of advanced electronic information technology by skilled service personnel, specifically, automotive service technicians. The theoretical basis of the study is Davis' technology acceptance model. The purpose of the study is to determine the effects of three external factors on the operation of the model: age, work experience, and education/certification level. The research design is in two parts, beginning with an onsite observation and interviews to establish the environment. During the second part of the research process a survey was administered to a sample of automotive service technicians. Results indicated significant inverse relationships between age and acceptance and between experience and acceptance. A significant positive relationship was shown between education, particularly certification, and acceptance

A multi-disciplinary perspective on emergent and future innovations in peer review [version 2; referees: 2 approved]

Peer review of research articles is a core part of our scholarly communication system. In spite of its importance, the status and purpose of peer review is often contested. What is its role in our modern digital research and communications infrastructure? Does it perform to the high standards with which it is generally regarded? Studies of peer review have shown that it is prone to bias and abuse in numerous dimensions, frequently unreliable, and can fail to detect even fraudulent research. With the advent of web technologies, we are now witnessing a phase of innovation and experimentation in our approaches to peer review. These developments prompted us to examine emerging models of peer review from a range of disciplines and venues, and to ask how they might address some of the issues with our current systems of peer review. We examine the functionality of a range of social Web platforms, and compare these with the traits underlying a viable peer review system: quality control, quantified performance metrics as engagement incentives, and certification and reputation. Ideally, any new systems will demonstrate that they out-perform and reduce the biases of existing models as much as possible. We conclude that there is considerable scope for new peer review initiatives to be developed, each with their own potential issues and advantages. We also propose a novel hybrid platform model that could, at least partially, resolve many of the socio-technical issues associated with peer review, and potentially disrupt the entire scholarly communication system. Success for any such development relies on reaching a critical threshold of research community engagement with both the process and the platform, and therefore cannot be achieved without a significant change of incentives in research environments

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe