Multiple cyclotron line-forming regions in GX 301-2

We present two observations of the high-mass X-ray binary GX 301-2 with NuSTAR, taken at different orbital phases and different luminosities. We find that the continuum is well described by typical phenomenological models, like a very strongly absorbed NPEX model. However, for a statistically acceptable description of the hard X-ray spectrum we require two cyclotron resonant scattering features (CRSF), one at ~35 keV and the other at ~50 keV. Even though both features strongly overlap, the good resolution and sensitivity of NuSTAR allows us to disentangle them at >=99.9% significance. This is the first time that two CRSFs are seen in GX 301-2. We find that the CRSFs are very likely independently formed, as their energies are not harmonically related and, if it were a single line, the deviation from a Gaussian shape would be very large. We compare our results to archival Suzaku data and find that our model also provides a good fit to those data. We study the behavior of the continuum as well as the CRSF parameters as function of pulse phase in seven phase bins. We find that the energy of the 35 keV CRSF varies smoothly as function of phase, between 30-38 keV. To explain this variation, we apply a simple model of the accretion column, taking the altitude of the line-forming region, the velocity of the in-falling material, and the resulting relativistic effects into account. We find that in this model the observed energy variation can be explained simply due to a variation of the projected velocity and beaming factor of the line forming region towards us.Comment: 18 pages, 10 figures, accepted for publication in A&

In silico modelling of tumour margin diffusion and infiltration: Review of current status

Extent: 16p.As a result of advanced treatment techniques, requiring precise target definitions, a need for more accurate delineation of the Clinical Target Volume (CTV) has arisen. Mathematical modelling is found to be a powerful tool to provide fairly accurate predictions for the Microscopic Extension (ME) of a tumour to be incorporated in a CTV. In general terms, biomathematical models based on a sequence of observations or development of a hypothesis assume some links between biological mechanisms involved in cancer development and progression to provide quantitative or qualitative measures of tumour behaviour as well as tumour response to treatment. Generally, two approaches are taken: deterministic and stochastic modelling. In this paper, recent mathematical models, including deterministic and stochastic methods, are reviewed and critically compared. It is concluded that stochastic models are more promising to provide a realistic description of cancer tumour behaviour due to being intrinsically probabilistic as well as discrete, which enables incorporation of patient-specific biomedical data such as tumour heterogeneity and anatomical boundaries.Fatemeh Leyla Moghaddasi, Eva Bezak, and Loredana Marc

Uqosp(2,2)U_q osp(2,2) Lattice Models

In this paper I construct lattice models with an underlying $U_q osp(2,2)$ superalgebra symmetry. I find new solutions to the graded Yang-Baxter equation. These {\it trigonometric} $R$-matrices depend on {\it three} continuous parameters, the spectral parameter, the deformation parameter $q$ and the $U(1)$ parameter, $b$, of the superalgebra. It must be emphasized that the parameter $q$ is generic and the parameter $b$ does not correspond to the `nilpotency' parameter of \cite{gs}. The rational limits are given; they also depend on the $U(1)$ parameter and this dependence cannot be rescaled away. I give the Bethe ansatz solution of the lattice models built from some of these $R$-matrices, while for other matrices, due to the particular nature of the representation theory of $osp(2,2)$, I conjecture the result. The parameter $b$ appears as a continuous generalized spin. Finally I briefly discuss the problem of finding the ground state of these models.Comment: 19 pages, plain LaTeX, no figures. Minor changes (version accepted for publication

Cyclotron resonant scattering feature simulations. I. Thermally averaged cyclotron scattering cross sections, mean free photon-path tables, and electron momentum sampling

Electron cyclotron resonant scattering features (CRSFs) are observed as absorption-like lines in the spectra of X-ray pulsars. A significant fraction of the computing time for Monte Carlo simulations of these quantum mechanical features is spent on the calculation of the mean free path for each individual photon before scattering, since it involves a complex numerical integration over the scattering cross section and the (thermal) velocity distribution of the scattering electrons. We aim to numerically calculate interpolation tables which can be used in CRSF simulations to sample the mean free path of the scattering photon and the momentum of the scattering electron. The tables also contain all the information required for sampling the scattering electron's final spin. The tables were calculated using an adaptive Simpson integration scheme. The energy and angle grids were refined until a prescribed accuracy is reached. The tables are used by our simulation code to produce artificial CRSF spectra. The electron momenta sampled during these simulations were analyzed and justified using theoretically determined boundaries. We present a complete set of tables suited for mean free path calculations of Monte Carlo simulations of the cyclotron scattering process for conditions expected in typical X-ray pulsar accretion columns (0.01<B/B_{crit}<=0.12, where B_{crit}=4.413x10^{13} G and 3keV<=kT<15keV). The sampling of the tables is chosen such that the results have an estimated relative error of at most 1/15 for all points in the grid. The tables are available online at http://www.sternwarte.uni-erlangen.de/research/cyclo.Comment: A&A, in pres

Spinning-Up: The Case of the Symbiotic X-Ray Binary 3A 1954+319

We present a timing and spectral analysis of the variable X-ray source 3A 1954+319, Our analysis is mainly based on an outburst serendipitously observed during INTEGRAL Key Program observations of the Cygnus region in 2008 fall and on the Swift/BAT longterm light curve, Previous observations, though sparse, have identified the source to be one of only nine known symbiotic X-ray binaries, i.e., systems composed of an accreting neutron star orbiting in a highly inhomogeneous medium around an M-giant companion. The spectrum of 3A 1954+319 above 20 keY can be best described by a broken power law model. The extremely long pulse period of approx.5.3 hours is clearly visible in the INTEGRAL/ISGRI light curve and confirmed through an epoch folding period search. Furthermore, the light curve allows us to determine a very strong spin up of -2x10(exp 4)h/h during the outburst. This spin up is confirmed by the pulse period evolution calculated from Swift/BAT data. The Swift/BAT data also show a long spin-down trend prior to the 2008 outburst. which is confirmed in archival INTEGRAL/ISGRI data. We discuss possible accretion models and geometries allowing for the transfer of such large amounts of angular momentum and investigate the harder spectrum of this outburst compared to previously published results

Mutation of daf‐2 extends lifespan via tissue‐specific effectors that suppress distinct life‐limiting pathologies

In aging Caenorhabditis elegans, as in higher organisms, there is more than one cause of death. C. elegans exhibit early death with a swollen, infected pharynx (P death), and later death with pharyngeal atrophy (p death). Interventions that alter lifespan can differentially affect frequency and timing of each type of death, generating complex survival curve shapes. Here, we use mortality deconvolution analysis to investigate how reduction of insulin/IGF-1 signaling (IIS), which increases lifespan (the Age phenotype), affects different forms of death. All daf-2 insulin/IGF-1 receptor mutants exhibit increased lifespan in the p subpopulation (p Age), while pleiotropic class 2 daf-2 mutants show an additional marked reduction in P death frequency. The latter is promoted by pharyngeal expression of the IIS-regulated DAF-16 FOXO transcription factor, and at higher temperature by reduced pharyngeal pumping rate. Pharyngeal DAF-16 also promotes p Age in class 2 daf-2 mutants, revealing a previously unknown role for the pharynx in the regulation of aging. Necropsy analysis of daf-2 interactions with the daf-12 steroid receptor implies that previously described opposing effects of daf-12 on daf-2 longevity are attributable to internal hatching of larvae, rather than complex interactions between insulin/IGF-1 and steroid signaling. These findings support the view that wild-type IIS acts through multiple distinct mechanisms which promote different life-limiting pathologies, each of which contribute to late-life mortality. This study further demonstrates the utility of mortality deconvolution analysis to better understand the genetics of lifespan

TAPBPR mediates peptide dissociation from MHC class I using a leucine lever.

Tapasin and TAPBPR are known to perform peptide editing on major histocompatibility complex class I (MHC I) molecules; however, the precise molecular mechanism(s) involved in this process remain largely enigmatic. Here, using immunopeptidomics in combination with novel cell-based assays that assess TAPBPR-mediated peptide exchange, we reveal a critical role for the K22-D35 loop of TAPBPR in mediating peptide exchange on MHC I. We identify a specific leucine within this loop that enables TAPBPR to facilitate peptide dissociation from MHC I. Moreover, we delineate the molecular features of the MHC I F pocket required for TAPBPR to promote peptide dissociation in a loop-dependent manner. These data reveal that chaperone-mediated peptide editing on MHC I can occur by different mechanisms dependent on the C-terminal residue that the MHC I accommodates in its F pocket and provide novel insights that may inform the therapeutic potential of TAPBPR manipulation to increase tumour immunogenicity.Wellcome PhD studentship (109076/Z/15/A). Wellcome Senior Research Fellowship (104647/Z/14/Z) South African Medical Research Council Bosch-Forschungsstiftung. Royal Society University Research Fellowship (UF100371)

Conducting Research with Stigmatized Populations: Practices, Challenges, and Lessons Learned

Conducting research with communities who are at risk of being stigmatized can be a challenging endeavor. It is often difficult to reach and recruit individuals for research purposes regarding a stigmatized condition or situation. Yet, researchers in our field have recognized the importance of work in this area and have individually developed a range of strategies to reach, recruit, and work with these populations. This workshop will invite researchers and practitioners to present, discuss, and compare strategies and experiences when working with stigmatized communities in the context of the ever-evolving nature of technology. The outcomes of the workshop will include an outline for an article that will summarize the strategies and practices discussed as well as identify the approaches that have led to the best outcomes across different populations

Modelling of Tirapazamine effects on solid tumour morphology

Bioreductive drugs are in clinical practice to exploit the resistance from tumour microenvironments especially in the hypoxic region of tumour. We pre-sented a tumour treatment model to capture the pharmacology of one of the most prominent bioreductive drugs, Tirapazamine (TPZ) which is in clinical trials I and II. We calculated solid tumour mass in our previous work and then integrated that model with TPZ infusion. We calculated TPZ cytotoxicity, concentration, penetra-tion with increasing distance from blood vessel and offered resistance from micro-environments for drug penetration inside the tumour while considering each cell as an individual entity. The impact of these factors on tumour morphology is also showed to see the drug behaviour inside animals/humans tumours. We maintained the heterogeneity factors in presented model as observed in real tumour mass es-pecially in terms of cells proliferation, cell movement, extracellular matrix (ECM) interaction, and the gradients of partial oxygen pressure (pO2) inside tumour cells during the whole growth and treatment activity. The results suggest that TPZ high concentration in combination with chemotherapy should be given to get maximum abnormal cell killing. This model can be a good choice for oncologists and re-searchers to explore more about TPZ action inside solid tumour