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.

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.

Investigation of Finish-cut of Microelectrodischarge Milling for Nano Surface Finish

In this article, the machining conditions to achieve nanometric surface roughness in finish cut microelectrodischarge milling were investigated. For a constant gap voltage, the effect of feed rate and capacitance was studied on average surface roughness (Ra) and maximum peak-to-valley roughness height (Ry). Statistical models were developed using a three-level, two-factor experimental design. The developed models minimized Ra and Ry by desirability function approach. Maximum desirability was found to be more than 98%. The minimum values of Ra and Ry were 23 and 173 nm, respectively, for 1.00 μm s-1 feed rate and 0.01 nF capacitance. Verification experiments were conducted to check the accuracy of the models, where the responses were found to be very close to the predicted values. Thus, the developed models can be used to generate nanometric level surface finish, which are useful for many applications in microelectromechanical systems.

Experimentally validated partial least squares model for dynamic line rating

This study presents a model based on partial least squares (PLS) regression for dynamic line rating (DLR). The model has been verified using data from field measurements, lab tests and outdoor experiments. Outdoor experimentation has been conducted both to verify the model predicted DLR and also to provide training data not available from field measurements, mainly heavily loaded conditions. The proposed model, unlike the direct measurement based DLR techniques, enables prediction of line rating for periods ahead of time whenever a reliable weather forecast is available. The PLS approach yields a very simple statistical model that accurately captures the physical performance of the conductor within a given environment without requiring a predetermination of parameters as required by many physical modelling techniques. Accuracy of the PLS model has been tested by predicting the conductor temperature for measurement sets other than those used for training. Being a linear model, it is straightforward to estimate the conductor ampacity for a set of predicted weather parameters. The PLS estimated ampacity has proven its accuracy through an outdoor experiment on a piece of the line conductor in real weather conditions.

Partial least squares model for dynamic rating of overhead line in wind intensive areas based on field measurements

This paper presents a statistical model for the thermal behaviour of the line model based on lab tests and field measurements. This model is based on Partial Least Squares (PLS) multi regression and is used for the Dynamic Line Rating (DLR) in a wind intensive area. DLR provides extra capacity to the line, over the traditional seasonal static rating, which makes it possible to defer the need for reinforcement the existing network or building new lines. The proposed PLS model has a number of appealing features; the model is linear, so it is straightforward to use for predicting the line rating for future periods using the available weather forecast. Unlike the available physical models, the proposed model does not require any physical parameters of the line, which avoids the inaccuracies resulting from the errors and/or variations in these parameters. The developed model is compared with physical model, the Cigre model, and has shown very good accuracy in predicting the conductor temperature as well as in determining the line rating for future time periods. 

Electron impact excitation of Mg VIII: Collision strengths, transition probabilities and theoretical EUV and soft X-ray line intensities for Mg VIII

Context: Mg VIII emission lines are observed in a range of astronomical objects such as the Sun, other cool stars and in the coronal line region of Seyfert galaxies. Under coronal conditions Mg VIII emits strongly in the extreme ultraviolet (EUV) and soft X-ray spectral regions which makes it an ideal ion for plasma diagnostics.

Aims. Two theoretical atomic models, consisting of 125 fine structure levels, are developed for the Mg VIII ion. The 125 levels arise from the 2s(2)2p, 2s(2)p2, 2p(3), 2s(2)3s, 2s(2)3p, 2s(2)3d, 2s2p3s, 2s2p3p, 2s2p3d, 2p(2)3s, 2p(2)3p and 2p(2)3d configurations. Electron impact excitation collision strengths and radiative transition probabilities are calculated for both Mg VIII models, compared with existing data, and the best model selected to generate a set of theoretical emission line intensities. The EUV lines, covering 312-790 angstrom, are compared with existing solar spectra (SERTS-89 and SUMER), while the soft X-ray transitions (69-97 angstrom) are examined for potential density diagnostic line ratios and also compared with the limited available solar and stellar observational data.

Methods. The R-matrix codes Breit-Pauli RMATRXI and RMATRXII are utilised, along with the PSTGF code, to calculate the collision strengths for two Mg VIII models. Collision strengths are averaged over a Maxwellian distribution to produce the corresponding effective collision strengths for use in astrophysical applications. Transition probabilities are also calculated using the CIV3 atomic structure code. The best data are then incorporated into the modelling code CLOUDY and line intensities generated for a range of electron temperatures and densities appropriate to solar and stellar coronal plasmas.

Results. The present effective collision strengths are compared with two previous calculations. Good levels of agreement are found with the most recent, but there are large differences with the other for forbidden transitions. The resulting line intensities compare favourably with the observed values from the SERTS-89 and SUMER spectra. Theoretical soft X-ray emission lines are presented and several density diagnostic line ratios examined, which are in reasonable agreement with the limited observational data available.

Vector bundles on the projective line and finite domination of chain complexes

We present an algebro-geometric approach to a theorem on finite domination of chain complexes over a Laurent polynomial ring. The approach uses extension of chain complexes to sheaves on the projective line, which is governed by a K-theoretical obstruction.