3' non-translated sequences in Drosophila cyclin B transcripts direct posterior pole accumulation late in oogenesis and peri-nuclear association in syncytial embryos

We have characterised forms of the Drosophila cyclin B transcript that differ as a result of a splicing event which removes a nucleotide segment from the 3' untranslated region. In oogenesis, both cyclin A RNA and a shorter form of the cyclin B transcript are seen in the cells of the germarium that are undergoing mitosis. The shorter cyclin B transcript alone is then detectable in the presumptive oocyte until stages 7-8 of oogenesis. Both cyclin A RNA and a longer form of the cyclin B RNA are then synthesised in the nurse cells during stages 9-11, to be deposited in the oocyte during stages 11-12. These transcripts become evenly distributed throughout the oocyte cytoplasm but, in addition, those of cyclin B become concentrated at the posterior pole. Examination of the distributions of RNAs transcribed from chimeric cyclin genes indicates that sequences in the 3' untranslated region of the larger cyclin B RNA are required both for it to become concentrated at the posterior pole and to direct those transcripts in the body of the syncytial embryo to their peri-nuclear localisation. These sequences are disrupted by the splicing event which generates smaller cyclin B transcripts

3' non-translated sequences in Drosophila cyclin B transcripts direct posterior pole accumulation late in oogenesis and peri-nuclear association in syncytial embryos

We have characterised forms of the Drosophila cyclin B transcript that differ as a result of a splicing event which removes a nucleotide segment from the 3' untranslated region. In oogenesis, both cyclin A RNA and a shorter form of the cyclin B transcript are seen in the cells of the germarium that are undergoing mitosis. The shorter cyclin B transcript alone is then detectable in the presumptive oocyte until stages 7-8 of oogenesis. Both cyclin A RNA and a longer form of the cyclin B RNA are then synthesised in the nurse cells during stages 9-11, to be deposited in the oocyte during stages 11-12. These transcripts become evenly distributed throughout the oocyte cytoplasm but, in addition, those of cyclin B become concentrated at the posterior pole. Examination of the distributions of RNAs transcribed from chimeric cyclin genes indicates that sequences in the 3' untranslated region of the larger cyclin B RNA are required both for it to become concentrated at the posterior pole and to direct those transcripts in the body of the syncytial embryo to their peri-nuclear localisation. These sequences are disrupted by the splicing event which generates smaller cyclin B transcripts

Expression of N-terminally truncated cyclin B in the Drosophila larval brain leads to mitotic delay at late anaphase

We have introduced an N-terminally truncated form of cyclin B into the Drosophila germ-line downstream of the yeast upstream activator that responds to GAL4. When such lines of flies are crossed to lines in which GAL4 is expressed in imaginal discs and larval brain, the majority of the resulting progeny die at the late pupal stage of development. Very rarely (< 0.1% of progeny) adults emerge that have a mutant phenotype typical of flies with mutations in genes required for the cell cycle; they have rough eyes, deformed wings, abnormal bristles, and die within hours of emergence. The brains of third instar larval progeny show an abnormally high proportion of mitotic cells containing overcondensed chromatids that have undergone anaphase separation, together with cells that cannot be assigned to a particular mitotic stage. Immunostaining indicates that these anaphase cells contain moderate levels of cyclin B, suggesting that persistent p34^(cdc2) kinase activity can prevent progression from anaphase into telophase

Expression of N-terminally truncated cyclin B in the Drosophila larval brain leads to mitotic delay at late anaphase

We have introduced an N-terminally truncated form of cyclin B into the Drosophila germ-line downstream of the yeast upstream activator that responds to GAL4. When such lines of flies are crossed to lines in which GAL4 is expressed in imaginal discs and larval brain, the majority of the resulting progeny die at the late pupal stage of development. Very rarely (< 0.1% of progeny) adults emerge that have a mutant phenotype typical of flies with mutations in genes required for the cell cycle; they have rough eyes, deformed wings, abnormal bristles, and die within hours of emergence. The brains of third instar larval progeny show an abnormally high proportion of mitotic cells containing overcondensed chromatids that have undergone anaphase separation, together with cells that cannot be assigned to a particular mitotic stage. Immunostaining indicates that these anaphase cells contain moderate levels of cyclin B, suggesting that persistent p34^(cdc2) kinase activity can prevent progression from anaphase into telophase

Securitization and the construction of security

Those interested in the construction of security in contemporary international politics have increasingly turned to the conceptual framework of `securitization'. This article argues that while an important and innovative contribution, the securitization framework is problematically narrow in three senses. First, the form of act constructing security is defined narrowly, with the focus on the speech of dominant actors. Second, the context of the act is defined narrowly, with the focus only on the moment of intervention. Finally, the framework of securitization is narrow in the sense that the nature of the act is defined solely in terms of the designation of threats. In outlining this critique, the article points to possibilities for developing the framework further as well as for the need for those applying it to recognize both limits of their claims and the normative implications of their analysis. I conclude by pointing to how the framework might fit within a research agenda concerned with the broader construction of security

On the use of CO2 laser induced surface patterns to modify the wettability of Poly(methyl methacrylate) (PMMA)

CO2 lasers can be seen to lend themselves to materials processing applications and have been used extensively in both research and industry. This work investigated the surface modification of PMMA with a CO2 laser in order to vary the wettability characteristics. The wettability characteristics of the PMMA were modified by generating a number of patterns of various topography on the surface using the CO2 laser. These induced patterns were trench and hatch with scan dimensions of 50 and 100 μm. Through white light interferometry it was found that for all laser patterned samples the surface roughness had significantly increased by up to 3.1 μm. The chemical composition of selected samples were explored using X-ray photoelectron spectroscopy and found that the surface oxygen content had risen by approximately 4% At. By using a sessile drop device it was found that, in comparison to the as-received sample, 50 μm dimensions gave rise to a more hydrophilic surface; whereas 100 μm dimensions gave rise to either no change in contact angle or an increase making the PMMA hydrophobic. This can be explained by combinations of surface roughness and γp contributing to the observed contact angle, in addition to the possibility of different wetting regimes taking place owed to the variation of topographies over the as-received and laser patterned samples

Prospective Evaluation of the Prognostic Implications of Improved Assay Performance With a Sensitive Assay for Cardiac Troponin I

ObjectivesThe purpose of this study was to investigate the prognostic implications of low-level increases in cardiac troponin I (cTnI) using a current-generation sensitive assay in patients with suspected acute coronary syndrome (ACS).BackgroundRecent enhancements in troponin assays have enabled resolution of the 99th percentile reference limit at progressively lower concentrations. However, the clinical significance of low-level increases with sensitive assays is still debated.MethodsWe measured cTnI using a sensitive assay (TnI-Ultra, Siemens Healthcare Diagnostics, Deerfield, Illinois) at baseline in 4,513 patients with non–ST-segment elevation ACS randomly assigned to ranolazine or placebo. We applied decision limits at the 99th percentile reference limit (0.04 μg/l), the cut point of the predecessor assay (0.1 μg/l), and 1 equivalent to elevation of creatine kinase–myocardial band (1.5 ng/ml).ResultsPatients with baseline cTnI ≥0.04 μg/l (n = 2,924) were at higher risk of death/myocardial infarction (MI) at 30 days than were patients with a negative cTnI (6.1% vs. 2.0%, p < 0.001). After adjusting for the TIMI (Thrombolysis In Myocardial Infarction) risk score, cTnI ≥0.04 μg/l was associated with a 3-fold (95% confidence interval: 2.0 to 4.4, p < 0.001) higher risk of death/MI at 30 days. Moreover, patients with low-level increases (0.04 μg/l to <0.1 μg/l), were at significantly higher risk of death/MI at 30 days (5.0% vs. 2.0%, p = 0.001) and death at 12 months (6.4% vs. 2.4%, p = 0.005) than were patients with cTnI <0.04 μg/l.ConclusionsLow-level increases in cTnI using a sensitive assay identify patients at higher risk of death or MI. These findings support current American College of Cardiology/American Heart Association recommendations defining MI, and the incremental value of newer, more sensitive assays in identifying high-risk patients with ACS

Increased efficiency of direct nanoimprinting on planar and curved bulk titanium through surface modification

In this work the direct transfer of nanopatterns into titanium is demonstrated. The nanofeatures are imprinted at room temperature using diamond stamps in a single step. We also show that the imprint properties of the titanium surface can be altered by anodisation yielding a significant reduction in the required imprint force for pattern transfer. The anodisation process is also utilised for curved titanium surfaces where a reduced imprint force is preferable to avoid sample deformation and damage. We finally demonstrate that our process can be applied directly to titanium rods

Concurrent cisplatin or cetuximab with radiotherapy for HPV-positive oropharyngeal cancer : Medical resource use, costs, and quality-adjusted survival from the De-ESCALaTE HPV trial

Background The De-ESCALaTE HPV trial confirmed the dominance of cisplatin over cetuximab for tumour control in patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC). Here, we present the analysis of health-related quality of life (HRQoL), resource use, and health care costs in the trial, as well as complete 2-year survival and recurrence. Materials and methods Resource use and HRQoL data were collected at intervals from the baseline to 24 months post treatment (PT). Health care costs were estimated using UK-based unit costs. Missing data were imputed. Differences in mean EQ-5D-5L utility index and adjusted cumulative quality-adjusted life years (QALYs) were compared using the Wilcoxon signed-rank test and linear regression, respectively. Mean resource usage and costs were compared through two-sample t-tests. Results 334 patients were randomised to cisplatin (n = 166) or cetuximab (n = 168). Two-year overall survival (97·5% vs 90·0%, HR: 3.268 [95% CI 1·451 to 7·359], p = 0·0251) and recurrence rates (6·4% vs 16·0%, HR: 2·67 [1·38 to 5·15]; p = 0·0024) favoured cisplatin. No significant differences in EQ-5D-5L utility scores were detected at any time point. At 24 months PT, mean difference was 0·107 QALYs in favour of cisplatin (95% CI: 0·186 to 0·029, p = 0·007) driven by the mortality difference. Health care costs were similar across all categories except the procurement cost and delivery of the systemic agent, with cetuximab significantly more expensive than cisplatin (£7779 [P < 0.001]). Consequently, total costs at 24 months PT averaged £13517 (SE: £345) per patient for cisplatin and £21064 (SE: £400) for cetuximab (mean difference £7547 [95% CI: £6512 to £8582]). Conclusions Cisplatin chemoradiotherapy provided more QALYs and was less costly than cetuximab bioradiotherapy, remaining standard of care for nonsurgical treatment of HPV-positive OPSCC