Computational Methods and Results for Structured Multiscale Models of Tumor Invasion

We present multiscale models of cancer tumor invasion with components at the molecular, cellular, and tissue levels. We provide biological justifications for the model components, present computational results from the model, and discuss the scientific-computing methodology used to solve the model equations. The models and methodology presented in this paper form the basis for developing and treating increasingly complex, mechanistic models of tumor invasion that will be more predictive and less phenomenological. Because many of the features of the cancer models, such as taxis, aging and growth, are seen in other biological systems, the models and methods discussed here also provide a template for handling a broader range of biological problems

A re-analysis of the spectrum of 2206-199

Recently Pettini, Hunstead, Smith and Mar, (PHSM 1991) performed an analysis of the Ly-alpha forest of QSO 2206-199N at very high resolution. On the basis of their observations they concluded that most Doppler parameters b = (square root of 2)(sigma) of Ly-alpha forest lines are below 22 km/s, with a range down to a few km/s and a median of 17 km/s. They also found a strong intrinsic correlation between Doppler parameter b and column density N. These results are in contrast to those of a similar study by Carswell, Lanzetta, Parnell, and Webb (CLPW 1991) at comparable resolution with the same instruments, who find that most of the Ly-alpha lines towards QSO 1100-264 have Doppler parameters above 15 km/s (median b = 34 km/s), and that there is no significant correlation between b and N. Whilst an intrinsic difference between the lines of sight to 2206-199 and to other QSO's can not be excluded a priori, previous disagreement between Doppler parameter estimates obtained by both groups pointed to a potential difference in estimation techniques and in the interpretation of the results. To investigate this possibility, the AAT/UCLES spectrum of 2206-199 obtained by PHSM were reanalyzed. The spectrum was extracted from the raw data and determined the line parameters using the method described by CLPW

The ATPase cycle of PcrA helicase and its coupling to translocation on DNA.

The superfamily 1 bacterial helicase PcrA has a role in the replication of certain plasmids, acting with the initiator protein (RepD) that binds to and nicks the double-stranded origin of replication. PcrA also translocates single-stranded DNA with discrete steps of one base per ATP hydrolyzed. Individual rate constants have been determined for the DNA helicase PcrA ATPase cycle when bound to either single-stranded DNA or a double-stranded DNA junction that also has RepD bound. The fluorescent ATP analogue 2'(3')-O-(N-methylanthraniloyl)ATP was used throughout all experiments to provide a complete ATPase cycle for a single nucleotide species. Fluorescence intensity and anisotropy stopped-flow measurements were used to determine rate constants for binding and release. Quenched-flow measurements provided the kinetics of the hydrolytic cleavage step. The fluorescent phosphate sensor MDCC-PBP was used to measure phosphate release kinetics. The chemical cleavage step is the rate-limiting step in the cycle and is essentially irreversible and would result in the bound ATP complex being a major component at steady state. This cleavage step is greatly accelerated by bound DNA, producing the high activation of this protein compared to the protein alone. The data suggest the possibility that ADP is released in two steps, which would result in bound ADP also being a major intermediate, with bound ADP.P(i) being a very small component. It therefore seems likely that the major transition in structure occurs during the cleavage step, rather than P(i) release. ATP rebinding could then cause reversal of this structural transition. The kinetic mechanism of the PcrA ATPase cycle is very little changed by potential binding to RepD, supporting the idea that RepD increases the processivity of PcrA by increasing affinity to DNA rather than affecting the enzymatic properties per se

The Deuterium Abundance in the z=0.7 absorber towards QSO PG1718+4807

We report a further analysis of the ratio of deuterium to hydrogen (D/H) using HST spectra of the z=0.701 Lyman limit system towards the QSO PG1718+481. Initial analyses of this absorber found it gave a high D/H value, 1.8 - 3.1 \times 10^{-4} (Webb et al. 1998), inconsistent with several higher redshift measurements. It is thus important to critically examine this measurement. By analysing the velocity widths of the DI, HI and metal lines present in this system, Kirkman et al. (2001) report that the additional absorption in the blue wing of the lya line can not be DI, with a confidence level of 98%. Here we present a more detailed analysis, taking into account possible wavelength shifts between the three sets of HST spectra used in the analysis. We find that the constraints on this system are not as strong as those claimed by Kirkman et al. The discrepancy between the parameters of the blue wing absorption and the parameters expected for DI is marginally worse than 1 sigma. Tytler et al.(1999) commented on the first analysis of Webb et al.(1997,1998), reporting the presence of a contaminating lower redshift Lyman limit system, with log[N(HI)] = 16.7 at z=0.602, which biases the N(HI) estimate for the main system. Here we show that this absorber actually has log[N(HI)] < 14.6 and does not impact on the estimate of N(HI) in the system of interest at z = 0.701. The purpose of the present paper is to highlight important aspects of the analysis which were not explored in previous studies, and hence help refine the methods used in future analyses of D/H in quasar spectra.Comment: 11 pages, 9 figures. Accepted by MNRA

The Density Spike in Cosmic-Ray-Modified Shocks: Formation, Evolution, and Instability

We examine the formation and evolution of the density enhancement (density spike) that appears downstream of strong, cosmic-ray-modified shocks. This feature results from temporary overcompression of the flow by the combined cosmic-ray shock precursor/gas subshock. Formation of the density spike is expected whenever shock modification by cosmic-ray pressure increases strongly. That occurence may be anticipated for newly generated strong shocks or for cosmic-ray-modified shocks encountering a region of higher external density, for example. The predicted mass density within the spike increases with the shock Mach number and with shocks more dominated by cosmic-ray pressure. We find this spike to be linearly unstable under a modified Rayleigh-Taylor instability criterion at the early stage of its formation. We confirm this instability numerically using two independent codes based on the two-fluid model for cosmic-ray transport. These two-dimensional simulations show that the instability grows impulsively at early stages and then slows down as the gradients of total pressure and gas density decrease. Observational discovery of this unstable density spike behind shocks, possibly through radio emission enhanced by the amplified magnetic fields would provide evidence for the existence of strongly cosmic-ray modified shock structures.Comment: 26 pages in Latex and 6 figures. Accepted to Ap

Interacting electrons on a quantum ring: exact and variational approach

We study a system of interacting electrons on a one-dimensional quantum ring using exact diagonalization and the variational quantum Monte Carlo method. We examine the accuracy of the Slater-Jastrow -type many-body wave function and compare energies and pair distribution functions obtained from the two approaches. Our results show that this wave function captures most correlation effects. We then study the smooth transition to a regime where the electrons localize in the rotating frame, which for the ultrathin quantum ring system happens at quite high electron density.Comment: 19 pages, 10 figures. Accepted for publication in the New Journal of Physic

Spatial Relationship between Solar Flares and Coronal Mass Ejections

We report on the spatial relationship between solar flares and coronal mass ejections (CMEs) observed during 1996-2005 inclusive. We identified 496 flare-CME pairs considering limb flares (distance from central meridian > 45 deg) with soft X-ray flare size > C3 level. The CMEs were detected by the Large Angle and Spectrometric Coronagraph (LASCO) on board the Solar and Heliospheric Observatory (SOHO). We investigated the flare positions with respect to the CME span for the events with X-class, M-class, and C-class flares separately. It is found that the most frequent flare site is at the center of the CME span for all the three classes, but that frequency is different for the different classes. Many X-class flares often lie at the center of the associated CME, while C-class flares widely spread to the outside of the CME span. The former is different from previous studies, which concluded that no preferred flare site exists. We compared our result with the previous studies and conclude that the long-term LASCO observation enabled us to obtain the detailed spatial relation between flares and CMEs. Our finding calls for a closer flare-CME relationship and supports eruption models typified by the CSHKP magnetic reconnection model.Comment: 7 pages; 4 figures; Accepted by the Astrophysical Journa

Enhanced Safety Surveillance of Influenza Vaccines in General Practice, Winter 2015-16: Feasibility Study

BACKGROUND: The European Medicines Agency (EMA) requires vaccine manufacturers to conduct enhanced real-time surveillance of seasonal influenza vaccination. The EMA has specified a list of adverse events of interest to be monitored. The EMA sets out 3 different ways to conduct such surveillance: (1) active surveillance, (2) enhanced passive surveillance, or (3) electronic health record data mining (EHR-DM). English general practice (GP) is a suitable setting to implement enhanced passive surveillance and EHR-DM. OBJECTIVE: This study aimed to test the feasibility of conducting enhanced passive surveillance in GP using the yellow card scheme (adverse events of interest reporting cards) to determine if it has any advantages over EHR-DM alone. METHODS: A total of 9 GPs in England participated, of which 3 tested the feasibility of enhanced passive surveillance and the other 6 EHR-DM alone. The 3 that tested EPS provided patients with yellow (adverse events) cards for patients to report any adverse events. Data were extracted from all 9 GPs' EHRs between weeks 35 and 49 (08/24/2015 to 12/06/2015), the main period of influenza vaccination. We conducted weekly analysis and end-of-study analyses. RESULTS: Our GPs were largely distributed across England with a registered population of 81,040. In the week 49 report, 15,863/81,040 people (19.57% of the registered practice population) were vaccinated. In the EPS practices, staff managed to hand out the cards to 61.25% (4150/6776) of the vaccinees, and of these cards, 1.98% (82/4150) were returned to the GP offices. Adverse events of interests were reported by 113 /7223 people (1.56%) in the enhanced passive surveillance practices, compared with 322/8640 people (3.73%) in the EHR-DM practices. CONCLUSIONS: Overall, we demonstrated that GPs EHR-DM was an appropriate method of enhanced surveillance. However, the use of yellow cards, in enhanced passive surveillance practices, did not enhance the collection of adverse events of interests as demonstrated in this study. Their return rate was poor, data entry from them was not straightforward, and there were issues with data reconciliation. We concluded that customized cards prespecifying the EMA's adverse events of interests, combined with EHR-DM, were needed to maximize data collection. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2016-015469