Biochemical and physiochemical characteristics of a pre-B cell stimulating factor produced by the plasmacytoma cell line LICR LON HMY2

We have characterized the pre-B cell colony stimulating activity (pre-B cell CSA) from LICR LON HMY2 conditioned medium (CM) by a variety of biochemical techniques. Pre-B cell CSA was found to be associated with a heat stable glycoprotein which has an isoelectric point of 8.3 and a mol. wt, as determined by polyacrylamide gel electrophoresis, of 28-32 kD. The relationship of this activity to previously described factors acting on cells of the B cell lineage is discussed.

Beowulf Hondbona: the Literary Context for Emending Line 1520b

In this article I consider the debate over whether line 1520b ought to be read as the emended “hond sweng” or the scribal “hord swenge.” It is a small point philologically but it raises interesting cultural and literary questions about the attitude of the Beowulf poet to arms and armour, to aggressive and defensive war gear, and to swords in particular. It has widely been assumed that swords are important in Beowulf and yet, the question of what their significance might be has received very little attention. Throughout the poem the hero is plagued by breaking, melting, and failing swords. He borrows, finds, and is given swords but unlike other English and Germanic heroes he is never identified with a single, great sword. I suggest that this is because, ultimately, Beowulf is conceived as a hondbana, a designation which has implications for what kind of a hero he proves to be.

Retroviral-mediated gene transfer of the human erythropoietin gene into a factor-dependent cell line, TF-1

The factor-dependent cell line, TF-1, established from a patient with erythroleukaemia, shows characteristics of immature erythroblasts. Addition of granulocyte-macrophage colony stimulating factor (GM-CSF) to the culture medium is required for long-term growth of the cells. Erythropoietin (Epo) can also be used to sustain TF-1 cells but for only limited periods (approximately a week). Low levels of both growth factors can act synergistically to maintain proliferation for a longer period of time than Epo alone. To eliminate the requirement of exogenous Epo for growth, TF-1 cells were co-cultured with a retroviral secreting cell line containing the human erythropoietin (hEpo) gene and a neomycin (neo) selectable marker. TF-1 cells which exhibited neo resistance (indicating infection by the retrovirus) were then grown in low concentrations of GM-CSF without the addition of Epo. Under these conditions growth of normal TF-1 cells was not sustained. The neo-resistant cells survived for more than 14 days indicating synergy between GM-CSF and the Epo synthesised by the co-cultured TF-1 cells. Radioimmunoassays performed on growth media detected concentrations up to 1 mU/ml of Epo, implying that stable integration of the retroviral vector and expression of the hEpo gene have been achieved.

Multidimensional poverty measurement in Europe:An application of the adjusted headcount approach

As awareness of the limitations of relying solely on income to measure poverty has become more widespread, attention has been increasingly focused on multi-dimensional approaches, to the point where the EU has adopted a multidimensional poverty and social exclusion target for 2020. The rationale advanced is that the computation of a multidimensional poverty index is an effective way of communicating in a political environment, and a necessary tool in order to monitor 27 different national situations. By contrast with the rather ad hoc way in which the EU 2020 poverty target has been framed and rationalised, the adjusted head count ratio applied here has a number of desirable axiomatic properties. It constitutes a significant improvement on union and intersection approaches and allows for the decomposition of multidimensional poverty in terms of dimensions of deprivation and socio-economic attributes. Since understanding poverty as multidimensional does not necessarily require constructing a multidimensional poverty index, on the basis of our analysis we provide a more general consideration of the value of developing a multidimensional index of poverty for the European Union.

Intermittent chemotherapy plus either intermittent or continuous cetuximab for first-line treatment of patients with KRAS wild-type advanced colorectal cancer (COIN-B): a randomised phase 2 trial

Background: Advanced colorectal cancer is treated with a combination of cytotoxic drugs and targeted treatments. However, how best to minimise the time spent taking cytotoxic drugs and whether molecular selection can refine this further is unknown. The primary aim of this study was to establish how cetuximab might be safely and effectively added to intermittent chemotherapy.

Methods: COIN-B was an open-label, multicentre, randomised, exploratory phase 2 trial done at 30 hospitals in the UK and one in Cyprus. We enrolled patients with advanced colorectal cancer who had received no previous chemotherapy for metastases. Randomisation was done centrally (by telephone) by the Medical Research Council Clinical Trials Unit using minimisation with a random element. Treatment allocation was not masked. Patients were assigned (1:1) to intermittent chemotherapy plus intermittent cetuximab or to intermittent chemotherapy plus continuous cetuximab. Chemotherapy was FOLFOX (folinic acid and oxaliplatin followed by bolus and infused fluorouracil). Patients in both groups received FOLFOX and weekly cetuximab for 12 weeks, then either had a planned interruption (those taking intermittent cetuximab) or planned maintenance by continuing on weekly cetuximab (continuous cetuximab). On RECIST progression, FOLFOX plus cetuximab or FOLFOX was recommenced for 12 weeks followed by further interruption or maintenance cetuximab, respectively. The primary outcome was failure-free survival at 10 months. The primary analysis population consisted of patients who completed 12 weeks of treatment without progression, death, or leaving the trial. We tested BRAF and NRAS status retrospectively. The trial was registered, ISRCTN38375681.

Findings: We registered 401 patients, 226 of whom were enrolled. Results for 169 with KRAS wild-type are reported here, 78 (46%) assigned to intermittent cetuximab and 91 (54%) to continuous cetuximab. 64 patients assigned to intermittent cetuximab and 66 of those assigned to continuous cetuximab were included in the primary analysis. 10-month failure-free survival was 50% (lower bound of 95% CI 39) in the intermittent group versus 52% (lower bound of 95% CI 41) in the continuous group; median failure-free survival was 12·2 months (95% CI 8·8–15·6) and 14·3 months (10·7–20·4), respectively. The most common grade 3–4 adverse events were skin rash (21 [27%] of 77 patients vs 20 [22%] of 92 patients), neutropenia (22 [29%] vs 30 [33%]), diarrhoea (14 [18%] vs 23 [25%]), and lethargy (20 [26%] vs 19 [21%]).

Interpretation: Cetuximab was safely incorporated in two first-line intermittent chemotherapy strategies. Maintenance of biological monotherapy, with less cytotoxic chemotherapy within the first 6 months, in molecularly selected patients is promising and should be validated in phase 3 trials.

A simple disc wind model for broad absorption line quasars

Approximately 20 per cent of quasi-stellar objects (QSOs) exhibit broad, blue-shifted absorption lines in their ultraviolet spectra. Such features provide clear evidence for significant outflows from these systems, most likely in the form of accretion disc winds. These winds may represent the ‘quasar’ mode of feedback that is often invoked in galaxy formation/evolution models, and they are also key to unification scenarios for active galactic nuclei (AGN) and QSOs. To test these ideas, we construct a simple benchmark model of an equatorial, biconical accretion disc wind in a QSO and use a Monte Carlo ionization/radiative transfer code to calculate the ultraviolet spectra as a function of viewing angle. We find that for plausible outflow parameters, sightlines looking directly into the wind cone do produce broad, blue-shifted absorption features in the transitions typically seen in broad absorption line (BAL) QSOs. However, our benchmark model is intrinsically X-ray weak in order to prevent overionization of the outflow, and the wind does not yet produce collisionally excited line emission at the level observed in non-BAL QSOs. As a first step towards addressing these shortcomings, we discuss the sensitivity of our results to changes in the assumed X-ray luminosity and mass-loss rate, Ṁwind. In the context of our adopted geometry, Ṁwind ∼ Ṁacc is required in order to produce significant BAL features. The kinetic luminosity and momentum carried by such outflows would be sufficient to provide significant feedback.

Electron-Impact Excitation Collision Strengths and Theoretical Line Intensities for Fine-Structure Transitions in S III

We present Maxwellian-averaged effective collision strengths for the electron-impact excitation of S III over a wide range of electron temperatures of astrophysical importance, log Te (K) = 3.0-6.0. The calculation incorporates 53 fine-structure levels arising from the six configurations—3s 23p 2, 3s3p 3, 3s 23p3d, 3s 23p4s, 3s 23p4p, and 3s 23p4d—giving rise to 1378 individual lines and is undertaken using the recently developed RMATRX II plus FINE95 suite of codes. A detailed comparison is made with a previous R-matrix calculation and significant differences are found for some transitions. The atomic data are subsequently incorporated into the modeling code CLOUDY to generate line intensities for a range of plasma parameters, with emphasis on allowed ultraviolet extreme-ultraviolet emission lines detected from the Io plasma torus. Electron density-sensitive line ratios are calculated with the present atomic data and compared with those from CHIANTI v7.1, as well as with Io plasma torus spectra obtained by Far-Ultraviolet Spectroscopic Explorer and Extreme-Ultraviolet Explorer. The present line intensities are found to agree well with the observational results and provide a noticeable improvement on the values predicted by CHIANTI.

Line-driven Disk Winds in Activ Galactic Nuclei: The Critical Importance of Ionization and Radiative Transfer

Accretion disk winds are thought to produce many of the characteristic features seen in the spectra of active galactic nuclei (AGNs) and quasi-stellar objects (QSOs). These outflows also represent a natural form of feedback between the central supermassive black hole and its host galaxy. The mechanism for driving this mass loss remains unknown, although radiation pressure mediated by spectral lines is a leading candidate. Here, we calculate the ionization state of, and emergent spectra for, the hydrodynamic simulation of a line-driven disk wind previously presented by Proga & Kallman. To achieve this, we carry out a comprehensive Monte Carlo simulation of the radiative transfer through, and energy exchange within, the predicted outflow. We find that the wind is much more ionized than originally estimated. This is in part because it is much more difficult to shield any wind regions effectively when the outflow itself is allowed to reprocess and redirect ionizing photons. As a result, the calculated spectrum that would be observed from this particular outflow solution would not contain the ultraviolet spectral lines that are observed in many AGN/QSOs. Furthermore, the wind is so highly ionized that line driving would not actually be efficient. This does not necessarily mean that line-driven winds are not viable. However, our work does illustrate that in order to arrive at a self-consistent model of line-driven disk winds in AGN/QSO, it will be critical to include a more detailed treatment of radiative transfer and ionization in the next generation of hydrodynamic simulations.