A survey of diffuse interstellar bands in the Andromeda galaxy: optical spectroscopy of M31 OB stars

We present the largest sample to-date of intermediate-resolution blue-to-red optical spectra of B-type supergiants in M31 and undertake the first survey of diffuse interstellar bands (DIBs) in this galaxy. Spectral classifications, radial velocities and interstellar reddenings are presented for 34 stars in three regions of M31. Radial velocities and equivalent widths are given for the 5780 and 6283 DIBs towards 11 stars. Equivalent widths are also presented for the following DIBs detected in three sightlines in M31: 4428, 5705, 5780, 5797, 6203, 6269, 6283, 6379, 6613, 6660, and 6993. All of these M31 DIB carriers reside in clouds at radial velocities matching those of interstellar Na I and/or H I. The relationships between DIB equivalent widths and reddening (E(B-V)) are consistent with those observed in the local ISM of the Milky Way. Many of the observed sightlines show DIB strengths (per unit reddening) which lie at the upper end of the range of Galactic values. DIB strengths per unit reddening are found (with 68% confidence), to correlate with the interstellar UV radiation field strength. The strongest DIBs are observed where the interstellar UV flux is lowest. The mean Spitzer 8/24 micron emission ratio in our three fields is slightly lower than that measured in the Milky Way, but we identify no correlation between this ratio and the DIB strengths in M31. Interstellar oxygen abundances derived from the spectra of three M31 H II regions in one of the fields indicate that the average metallicity of the ISM in that region is 12 + log[O/H] = 8.54 +- 0.18, which is approximately equal to the value in the solar neighbourhood

A coupled drug kinetics-cell cycle model to analyse the response of human cells to intervention by topotecan

A model describing the response of the growth of single human cells in the absence and presence of the anti-cancer agent topotecan (TPT) is presented. The model includes a novel coupling of both the kinetics of TPT and cell cycle responses to the agent. By linking the models in this way, rather than using separate (disjoint) approaches, it is possible to illustrate how the drug perturbs the cell cycle. The model is compared to experimental in vitro cell cycle response data (comprising single cell descriptors for molecular and behavioural events), showing good qualitative agreement for a range of TPT dose levels

Visualization of diffusion limited antimicrobial peptide attack on supported lipid membranes

Understanding the mechanism of action of antimicrobial peptides (AMP) is fundamental to the development and design of peptide based antimicrobials. Utilizing fast-scan atomic force microscopy (AFM) we detail the attack of an AMP on both prototypical prokaryotic (DOPC:DOPG) and eukaryotic (DOPC:DOPE) model lipid membranes on the nanoscale and in real time. Previously shown to have a favourable therapeutic index, we study Smp43, an AMP with a helical-hinge-helical topology isolated from the venom of the North African scorpion Scorpio maurus palmatus. We observe the dynamic formation of highly branched defects being supported by 2D diffusion models and further experimental data from liposome leakage assays and quartz crystal microbalance-dissipation (QCM-D) analysis, we propose that Smp43 disrupts these membranes via a common mechanism, which we have termed ‘diffusion limited disruption’ that encompasses elements of both the carpet model and the expanding pore mechanism

Plasma exchange in focal necrotizing glomerulonephritis without anti-GBM antibodies

Plasma exchange in focal necrotizing glomerulonephritis without anti-GBM antibodies. To determine whether plasma exchange was of additional benefit in patients treated with oral immunosuppressive drugs for focal necrotizing glomerulonephritis (without anti-GBM antibodies), we performed a randomized controlled trial with stratification for renal function on entry Forty-eight cases were analyzed, 25 in the treatment group (plasma exchange, prednisolone, cyclophosphamide and azathioprine) and 23 in the control group (drug therapy only). There was no difference in outcome in patients presenting with serum creatinine < 500 µmol/liter (N = 17), or > 500 µmol/liter but not on dialysis (N = 12), all but one of whom had improved by four weeks. However, patients who were initially dialysis-dependent (N = 19) were more likely to have recovered renal function (P = 0.041) if treated with plasma exchange as well as drugs (10 of 11) rather than with drugs alone (3 of 8). Long-term follow-up showed that improvement in renal function was generally maintained. The results of this trial confirm that focal necrotizing glomerulonephritis related to systemic vasculitis responds well to immunosuppressive drugs when treatment is started early, and suggest that plasma exchange is of additional benefit in dialysis-dependent cases

Phase II study of TP300 in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma

Background: TP300, a recently developed synthetic camptothecin analogue, is a highly selective topoisomerase I inhibitor. A phase I study showed good safety and tolerability. As camptothecins have proven active in oesophago-gastric adenocarcinomas, in this phase II study we assessed the efficacy and safety of TP300 in patients with gastric or gastro-oesophageal junction (GOJ) adenocarcinomas. Methods: Eligible patients had metastatic or locally advanced gastric or Siewert Types II or III GOJ inoperable adenocarcinoma. Patients were chemotherapy naïve unless this had been administered in the perioperative setting. TP300 was administered as a 1-h intravenous infusion every 3 weeks (a cycle) for up to 6 cycles at a starting dose of 8 mg/m2 with intra-patient escalation to 10 mg/m2 from cycle 2 in the absence of dose-limiting toxicity. Tumour responses (RECIST 1.1) were assessed every 6 weeks. Toxicity was recorded by NCI-CTCAE version 3.0. Using a modified two-stage Simon design (Stage I and II), a total of 43 patients were to be included providing there were 3 of 18 patients with objective response in Stage I of the study. Results: In Stage I of the study 20 patients (14 males, 6 females), median age 67 years (range 40 − 82), performance status ECOG 0/1, with GC [14] or GOJ carcinoma [6] were enrolled. Of the 16 evaluable patients, 11 received the planned dose increase to 10 mg/m2 at cycle 2, 2 decreased to 6 mg/m2, and 3 continued on 8 mg/m2. There were no objective responses after 2 cycles of treatment. Twelve patients had stable disease for 1 − 5 months and 4 had progressive disease. Median progression free survival (PFS) was 4.1 months (CI [1.6 − 4.9]), median time to progression (TTP) was 2.9 months (CI [1.4 − 4.2]). Grade 3/4 toxicities (worst grade all cycles) included 7 patients (35 %) with neutropenia, 4 patients (20 %) with anaemia, 2 patients (10 %) with thrombocytopenia, and 3 patients (15 %) with fatigue. This study was terminated at the end of Stage I due to a lack of the required (3/18) responders. Conclusions: This study of TP300 showed good drug tolerability but it failed to demonstrate sufficient efficacy as measured by radiological response

Lipid coated liquid crystal droplets for the on-chip detection of antimicrobial peptides

We describe a novel biosensor based on phospholipid-coated nematic liquid crystal (LC) droplets and demonstrate the detection of Smp43, a model antimicrobial peptide (AMP) from the venom of North African scorpion Scorpio maurus palmatus. Mono-disperse lipid-coated LC droplets of diameter 16.7 ± 0.2 μm were generated using PDMS microfluidic devices with a flow-focusing configuration and were the target for AMPs. The droplets were trapped in a bespoke microfluidic trap structure and were simultaneously treated with Smp43 at gradient concentrations in six different chambers. The disruption of the lipid monolayer by the Smp43 was detected (<6 μM) at concentrations well within its biologically active range, indicated by a dramatic change in the appearance of the droplets associated with the transition from a typical radial configuration to a bipolar configuration, which is readily observed by polarizing microscopy. This suggests the system has feasibility as a drug-discovery screening tool. Further, compared to previously reported LC droplet biosensors, this LC droplet biosensor with a lipid coating is more biologically relevant and its ease of use in detecting membrane-related biological processes and interactions has the potential for development as a reliable, low-cost and disposable point of care diagnostic tool

Fracture toughness of the cancellous bone of FNF femoral heads in relation to its microarchitecture

This study considers the relationship between microarchitecture and mechanical properties for cancellous bone specimens collected from a cohort of patients who had suffered fractured necks of femur. OP is an acute skeletal condition with huge socioeconomic impact [1] and it is associated with changes in both bone quantity and quality [2], which affect greatly the strength and toughness of the tissue [3].Support was provided by the EPSRC (EP/K020196: Point-ofCare High Accuracy Fracture Risk Prediction), the UK Department of Transport under the BOSCOS (Bone Scanning for Occupant Safety) project, and approved by Gloucester and Cheltenham NHS Trust hospitals under ethical consent (BOSCOS – Mr. Curwen CI REC ref 01/179G)

Simulations and experimental demonstrations of encoding for X-ray coherent scattering

Diffraction data may be measured using approaches that lead to ambiguity in the interpretation of scattering distributions. Thus, the encoding and decoding of coherent scatter distributions have been considered with a view to enabling unequivocal data interpretation. Two encoding regimes are considered where encoding occurs between the X-ray source and sample, and where the encoder is placed between the sample and detector. In the first case, the successful recovery of diffraction data formed from the interrogation of powder samples with annular incident beams is presented using a coded aperture approach. In a second regime, encoding of Debye cones is shown to enable recovery of sample position relative to the detector. The errors associated with both regimes are considered and the advantages of combining both discussed

Sheep Updates 2005 - Part 1

This session covers seven papers from different authors: Boosting lambing percentages of WA sheep flocks. R.W. Kelly CSIRO Livestock Industries, Floreat WA , R. Kingwell Department of Agriculture WA, Kiwis can fly - 30% higher lambing in 15 years, AR Bray, Meat and Wool New Zealand, Wellington, New Zealand Rams are not a trivial expense, so what can you do to maximise on your investment? Chri Oldham, Department of Agriculture Western Australia, Graeme Martin, University of West Australia. Care for mun - fetal programming, lamb survival and lifetime performance. RW Kelly CSIRO Livestock Industries, Floreat WA Boost lamb survival - select calm ewes, D Blanch University of western Australia, D Ferguson CSIRO FD McMaster Lab, NSW Getting high marking percentages in WA, Keith Crocker, Department of Agriculture Western Australia. Healthy, Welfare and Wise! Di Evans, Department of Agriculture Western Australi

Climate oscillations, glacial refugia, and dispersal ability: factors influencing the genetic structure of the least salmonfly, Pteronarcella badia (Plecoptera), in Western North America

Background: Phylogeographic studies of aquatic insects provide valuable insights into mechanisms that shape the genetic structure of communities, yet studies that include broad geographic areas are uncommon for this group. We conducted a broad scale phylogeographic analysis of the least salmonfly Pteronarcella badia (Plecoptera) across western North America. We tested hypotheses related to mode of dispersal and the influence of historic climate oscillations on population genetic structure. In order to generate a larger mitochondrial data set, we used 454 sequencing to reconstruct the complete mitochondrial genome in the early stages of the project. Results: Our analysis revealed high levels of population structure with several deeply divergent clades present across the sample area. Evidence from five mitochondrial genes and one nuclear locus identified a potentially cryptic lineage in the Pacific Northwest. Gene flow estimates and geographic clade distributions suggest that overland flight during the winged adult stage is an important dispersal mechanism for this taxon. We found evidence of multiple glacial refugia across the species distribution and signs of secondary contact within and among major clades. Conclusions: This study provides a basis for future studies of aquatic insect phylogeography at the inter-basin scale in western North America. Our findings add to an understanding of the role of historical climate isolations in shaping assemblages of aquatic insects in this region. We identified several geographic areas that may have historical importance for other aquatic organisms with similar distributions and dispersal strategies as P. badia. This work adds to the ever-growing list of studies that highlight the potential of next-generation DNA sequencing in a phylogenetic context to improve molecular data sets from understudied groups