Simulating Poynting Flux Acceleration in the Laboratory with Colliding Laser Pulses

We review recent PIC simulation results which show that double-sided irradiation of a thin over-dense plasma slab with ultra-intense laser pulses from both sides can lead to sustained comoving Poynting flux acceleration of electrons to energies much higher than the conventional ponderomotive limit. The result is a robust power-law electron momentum spectrum similar to astrophysical sources. We discuss future ultra-intense laser experiments that may be used to simulate astrophysical particle acceleration.Comment: Paper accepted for publication in the Astrophysics and Space Science, Volume for HEDLA06 conference proceedings, edited by G. Kyrala, in pres

Computer modeling of diabetes and Its transparency: a report on the Eighth Mount Hood Challenge

Objectives The Eighth Mount Hood Challenge (held in St. Gallen, Switzerland, in September 2016) evaluated the transparency of model input documentation from two published health economics studies and developed guidelines for improving transparency in the reporting of input data underlying model-based economic analyses in diabetes. Methods Participating modeling groups were asked to reproduce the results of two published studies using the input data described in those articles. Gaps in input data were filled with assumptions reported by the modeling groups. Goodness of fit between the results reported in the target studies and the groups’ replicated outputs was evaluated using the slope of linear regression line and the coefficient of determination (R2). After a general discussion of the results, a diabetes-specific checklist for the transparency of model input was developed. Results Seven groups participated in the transparency challenge. The reporting of key model input parameters in the two studies, including the baseline characteristics of simulated patients, treatment effect and treatment intensification threshold assumptions, treatment effect evolution, prediction of complications and costs data, was inadequately transparent (and often missing altogether). Not surprisingly, goodness of fit was better for the study that reported its input data with more transparency. To improve the transparency in diabetes modeling, the Diabetes Modeling Input Checklist listing the minimal input data required for reproducibility in most diabetes modeling applications was developed. Conclusions Transparency of diabetes model inputs is important to the reproducibility and credibility of simulation results. In the Eighth Mount Hood Challenge, the Diabetes Modeling Input Checklist was developed with the goal of improving the transparency of input data reporting and reproducibility of diabetes simulation model results

The Dyad Symmetry Element of Epstein-Barr Virus Is a Dominant but Dispensable Replication Origin

OriP, the latent origin of Epstein-Barr virus (EBV), consists of two essential elements: the dyad symmetry (DS) and the family of repeats (FR). The function of these elements has been predominantly analyzed in plasmids transfected into transformed cells. Here, we examined the molecular functions of DS in its native genomic context and at an ectopic position in the mini-EBV episome. Mini-EBV plasmids contain 41% of the EBV genome including all information required for the proliferation of human B cells. Both FR and DS function independently of their genomic context. We show that DS is the most active origin of replication present in the mini-EBV genome regardless of its location, and it is characterized by the binding of the origin recognition complex (ORC) allowing subsequent replication initiation. Surprisingly, the integrity of oriP is not required for the formation of the pre-replicative complex (pre-RC) at or near DS. In addition we show that initiation events occurring at sites other than the DS are also limited to once per cell cycle and that they are ORC-dependent. The deletion of DS increases initiation from alternative origins, which are normally used very infrequently in the mini-EBV genome. The sequence-independent distribution of ORC-binding, pre-RC-assembly, and initiation patterns indicates that a large number of silent origins are present in the mini-EBV genome. We conclude that, in mini-EBV genomes lacking the DS element, the absence of a strong ORC binding site results in an increase of ORC binding at dispersed sites

Zinc Coordination Is Required for and Regulates Transcription Activation by Epstein-Barr Nuclear Antigen 1

Epstein-Barr Nuclear Antigen 1 (EBNA1) is essential for Epstein-Barr virus to immortalize naïve B-cells. Upon binding a cluster of 20 cognate binding-sites termed the family of repeats, EBNA1 transactivates promoters for EBV genes that are required for immortalization. A small domain, termed UR1, that is 25 amino-acids in length, has been identified previously as essential for EBNA1 to activate transcription. In this study, we have elucidated how UR1 contributes to EBNA1's ability to transactivate. We show that zinc is necessary for EBNA1 to activate transcription, and that UR1 coordinates zinc through a pair of essential cysteines contained within it. UR1 dimerizes upon coordinating zinc, indicating that EBNA1 contains a second dimerization interface in its amino-terminus. There is a strong correlation between UR1-mediated dimerization and EBNA1's ability to transactivate cooperatively. Point mutants of EBNA1 that disrupt zinc coordination also prevent self-association, and do not activate transcription cooperatively. Further, we demonstrate that UR1 acts as a molecular sensor that regulates the ability of EBNA1 to activate transcription in response to changes in redox and oxygen partial pressure (pO2). Mild oxidative stress mimicking such environmental changes decreases EBNA1-dependent transcription in a lymphoblastoid cell-line. Coincident with a reduction in EBNA1-dependent transcription, reductions are observed in EBNA2 and LMP1 protein levels. Although these changes do not affect LCL survival, treated cells accumulate in G0/G1. These findings are discussed in the context of EBV latency in body compartments that differ strikingly in their pO2 and redox potential

Relativistic Laser-Matter Interaction and Relativistic Laboratory Astrophysics

The paper is devoted to the prospects of using the laser radiation interaction with plasmas in the laboratory relativistic astrophysics context. We discuss the dimensionless parameters characterizing the processes in the laser and astrophysical plasmas and emphasize a similarity between the laser and astrophysical plasmas in the ultrarelativistic energy limit. In particular, we address basic mechanisms of the charged particle acceleration, the collisionless shock wave and magnetic reconnection and vortex dynamics properties relevant to the problem of ultrarelativistic particle acceleration.Comment: 58 pages, 19 figure

On the design of experiments for the study of relativistic nonlinear optics in the limit of single-cycle pulse duration and single-wavelength spot size

We propose a set of experiments with the aim of studying for the first time relativistic nonlinear optics in the fundamental limits of single-cycle pulse duration and single-wavelength spot size. The laser system that makes this work possible is now operating at the Center for Ultrafast Optical Science at the University of Michigan. Its high repetition rate (1 kHz) will make it possible to perform a detailed investigation of relativistic effects in this novel regime. This study has the potential to make the field of relativistic optics accessible to a wider community and to open the door for real-world applications of relativistic optics, such as electron/ion acceleration and neutron and positron production.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45803/1/11452_2005_Article_253.pd