A class of almost C_0(K)-C*-algebras

We consider in this paper the family of exponential Lie groups Gn,µ, whose Lie algebra is an extension of the Heisenberg Lie algebra by the reals and whose quotient group by the centre of the Heisenberg group is an ax + b-like group. The C*-algebras of the groups Gn,µ give new examples of almost C0(K)-C*-algebras.

RAS mutations and cetuximab in locally advanced rectal cancer: results of the EXPERT-C trial.

Background: RAS mutations predict resistance to anti-epidermal growthfactor receptor (EGFR) monoclonal antibodies in metastatic colorectal cancer. We analysed RAS mutations in 30 non-metastatic rectal cancer patients treated with or without cetuximab within the 31 EXPERT-C trial.

Methods: Ninety of 149 patients with tumours available for analysis were KRAS/BRAF wild-type, and randomly assigned to capecitabine plus oxaliplatin (CAPOX) followed by chemoradiotherapy, surgery and adjuvant CAPOX or the same regimen plus cetuximab (CAPOX-C). Of these, four had a mutation of NRAS exon 3, and 84 were retrospectively analysed for additional KRAS (exon 4) and NRAS (exons 2/4) mutations by using bi-directional Sanger sequencing. The effect of cetuximab on study end-points in the RAS wild-type population was analysed.

Results: Eleven (13%) of 84 patients initially classified as KRAS/BRAF wild-type were found to have a mutation in KRAS exon 4 (11%) or NRAS exons 2/4 (2%). Overall, 78/149 (52%) assessable patients were RAS wild-type (CAPOX, n = 40; CAPOX-C, n = 38). In this population, after a median follow-up of 63.8 months, in line with the initial analysis, the addition of cetuximab was associated with numerically higher, but not statistically significant, rates of complete response (15.8% versus 7.5%, p = 0.31), 5-year progression-free survival (75.5% versus 67.5%, hazard ratio (HR) 0.61, p = 0.25) and 5-year overall survival (83.8% versus 70%, HR 0.54, p = 0.20).

Conclusions: RAS mutations beyond KRAS exon 2 and 3 were identified in 17% of locally advanced rectal cancer patients. Given the small sample size, no definitive conclusions on the effect of additional RAS mutations on cetuximab treatment in this setting can be drawn and further investigation of RAS in larger studies is warranted.

BRCA1 transcriptionally regulates genes associated with the basal breast cancer phenotype

Background Ten to twenty per cent of breast tumours exhibit a basallike genetic profile and these tumours carry a poor prognosis. Breast tumours which contain germline mutations for BRCA1 commonly exhibit a molecular profile similar to basal breast tumours. BRCA1 is a tumour suppressor gene which is mutated in up to 5–10% of breast cancer cases and is involved in multiple cellular processes including DNA damage control, cell cycle checkpoint control, apoptosis, ubiquitination and transcriptional regulation.

Methods Microarray-based profiling was carried out using the HCC1937EV and HCC1937BR breast cancer cell lines. Basal gene and protein expression levels were analysed by qRT-PCR and western blotting. ChIP analyses were performed and demonstrated that BRCA1 regulates basal gene expression through a transcriptional mechanism involving c-myc.

Results We have previously carried out microarray-based expression profiling to examine differences in gene expression when BRCA1 is reconstituted in BRCA1 mutated HCC1937 breast cancer cells. We observed that p-cadherin and the cytokeratin 5 and cytokeratin 17 genes, which are strongly correlated with the basal phenotype, are differentially expressed when BRCA1 is reconstituted. In addition, qRT-PCR and ChIP analysis of BRCA1 reconstituted cells show that BRCA1 represses the expression of these basal genes by a transcriptional mechanism. Furthermore, abrogation of endogenous BRCA1 protein in the T47D cell line using siRNA results in reexpression of these basal genes, suggesting that BRCA1 expression levels may be important in basal gene expression. We have also demonstrated that BRCA1 is physically associated with the promoter regions of basal genes through an association with c-myc. Consequently, we have confirmed that siRNA inhibition of c-myc in T47D cells results in re-expression of these genes.

Conclusions Our results suggest that BRCA1 is involved in the transcriptional regulation of genes associated with the basal phenotype and that BRCA1 controls basal gene expression through a transcriptional mechanism involving c-myc. Further work is now concentrating on defining the relationship between BRCA1 and basal gene expression and how this may affect clinical responses to breast cancer chemotherapy.

An Innovative teaching tool for students is it Appropriate?

Background: Clinical supervision takes place once the newly qualified nurse is employed in clinical practice. However, often the variety and diversity of nursing jobs can result in a hit and miss delivery of supervision training. By introducing training uniformly at undergraduate stage a more seamless transition may occur (McColgan K, Rice C. 2012).

There is an increased interest in higher education in the use of online learning resources for students. As part completion of a DNP an App. for training students in clinical supervision was developed.

Aim: The creation of a clinical supervision training App. for use in undergraduate nursing.

Objectives:
•To develop a teaching tool that is up to date, current and easily accessible to students.
•To introduce supervision training for undergraduate nursing students
•To motivate the undergraduate nursing student to identify examples from their clinical experience to encourage change and promote professional development.

Approach:
Stage 1
In 2010/11 informal inquiries with senior nurses regarding the introduction of supervision training in undergraduate nursing
Stage 2
A review of UK supervision training.
Stage 3
Template production of teaching tool.
Stage 4
Collaboration with a computer technician to transfer multimedia outputs onto an App.
Stage 5
App. piloted with lecturers (n=4) and post registration students (n=20).
Stage 6
Minor alterations made to App. design template
Stage 7
App. included in an experimental study looking at online learning versus blended learning June 2013 (n=61, n=63)

Conclusion: A collaborative approach to the development of any educational programme is essential to ensure the success of the final teaching product (McCutcheon 2013). The end result is that this App. could be:
•Made available to nurses in the UK.
•Adapted to suit other healthcare professionals and students.
•Used as a prototype for other healthcare related subjects.

McColgan K., Rice C. (2012) An online training resource for clinical supervision. Nursing Standard, 26(24) 35-39.
McCutcheon K. (2013) Development of a multi-media book for clinical supervision training in an undergraduate nursing programme. Journal of Nursing Education and Practice, 3(5) 31-38.

Negative photoion spectroscopy of the core-excited bromo- chloro-alkanes, Br(CH2)(n) Cl, n=1-4

Polar photodissociation of a set of bromo-chloro-alkanes in the vicinity of the Br 3d core edge has been observed for the first time. It is shown that negative photoion spectroscopy is a powerful tool for investigating the various decay mechanisms of core-excited molecules. Analysis of these results indicates that the observed polar photodissociation arises from two competing spectator Auger decay processes in which the molecule can dissociate either before or after the core hole relaxation.

Persistently raised C-reactive protein levels are associated with advanced periodontal disease

Objective: The aim was to investigate whether there was an association between periodontitis or tooth loss in a homogeneous group of 60-70-year-old Western European men and either a sustained high or low level of C-reactive protein (CRP).
Material and Methods: Men enrolled in a cohort study of cardiovascular disease in Northern Ireland were screened in 1990-1994 and rescreened in 2001-2004, when a periodontal examination was completed. High-sensitivity CRP was measured from fasting blood samples. There were 806 men with six or more teeth who had either a high level (>3 mg/l) or a lower level of CRP at both time points. Multivariate analysis was carried out using logistic regression with adjustment for possible confounders. Models were constructed with the CRP level as the outcome variable and various measures of periodontal status (low and high threshold periodontitis) or tooth loss as predictor variables. Confounders included in the analysis were known cardiovascular risk factors of age, smoking, diabetes, BMI and socioeconomic status.
Results: There were 67 men who had a high value of CRP (>3 mg/l) and 739 men who had a CRP value =3 mg/l at both time points. The unadjusted odds ratio (OR) for advanced periodontitis to be associated with high CRP was 3.62, p=0.0003. The association was somewhat attenuated but remained significant (OR=2.49, p=0.02) after adjustment for confounders. A high level of tooth loss was also associated with high CRP with an adjusted OR of 2.17, p=0.008. Low threshold periodontitis was not associated with the level of CRP.
Conclusion: There was an association between advanced periodontitis and elevated CRP levels as measured at two time points at a 10-year interval in the 60-70-year-old European males investigated. This association was adjusted for various cardiovascular risk factors. There was also an association between high levels of tooth loss and high CRP in the men studied.

Electrooxidation of the iodides [C(4)mim]I, LiI, NaI, KI, RbI, and CsI in the room temperature ionic liquid [C(4)mim][NTf2]

The electrochemical oxidation of 1-butyl-3-methylimidazolium iodide, [C(4)mim]I, has been investigated by cyclic voltammetry at a platinum microelectrode at varying concentrations in the RTIL 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [C(4)mim][NTf2]. Two oxidation peaks were observed. The first peak is assigned to the oxidation of iodide to triiodide, in an overall two-electron process: 3I(-)- 2e(-) -> I-3(-). At higher potentials, the electrogenerated triiodide oxidizes to iodine, in an overall one-electron process: I-3(-) - e(-) -> 3/2I(2). An average diffusion coefficient, D, for I- of 1.55 x 10(-11) m(2) s(-1) was obtained. A digital simulation program was used to simulate the voltammetric response, and kinetic parameters were successfully extracted. The parameters deduced from the simulation include D for I-, I-3(-), and I-2 and K-eq,K-2, the equilibrium constant for the reaction of iodide and iodine to form triiodide. Values for these parameters are of the same order as those previously published for the oxidation of Br- in the same RTIL [Allen et al. J. Electroanal. Chem. 2005, 575, 311]. Next, the cyclic voltammetry of five different inorganic iodide salts was studied by dissolving small amounts of the solid in [C(4)mim][NTf2]. Similar oxidation peaks were observed, revealing diffusion coefficients of ca. 0.55, 1.14, 1.23, 1.44, and 1.33 x 10(-11) m(2) s(-1) and solubilities of 714, 246, 54, 83, and 36 mM for LiI, NaI, KI, RbI, and CsI, respectively. The slightly smaller diffusion coefficients for the XI salts (compared to [C(4)mim]I) may indicate that I- is ion-paired with Li+, Na+, K+, Rb+, and Cs+ in the RTIL medium.

Presbyterian Religion, Historiography and Ulster Scots Identity, c. 1800 to 1914

The links between Presbyterians in Scotland and the north of Ireland are obvious but have been largely ignored by historians of the nineteenth century. This article addresses this gap by showing how Ulster Presbyterians considered their relationship with their Scottish co-religionists and how they used the interplay of religious and ethnic considerations this entailed to articulate an Ulster Scots identity. For Presbyterians in Ireland, their Scottish origins and identity represented a collection of ideas that could be deployed at certain times for specific reasons – theological orthodoxy, civil and religious liberty, and certain character traits such as hard work, courage, and soberness. Ideas about the Scottish identity of Presbyterianism were reawakened for a more general audience in the first half of the nineteenth century, during the campaign for religious reform and revival within the Irish church, and were expressed through a distinctive denominational historiography inaugurated by James Seaton Reid. The formulation of a coherent narrative of Presbyterian religion and the improvement of Ulster laid the religious foundations of a distinct Ulster Scots identity and its utilization by unionist opponents of Home Rule between 1885 and 1914.

Vitamins C and E for prevention of pre-eclampsia in women with type 1 diabetes (DAPIT): a randomised placebo-controlled trial.

Background
Results of several trials of antioxidant use during pregnancy have not shown a reduction in pre-eclampsia, but the eff ect in women with diabetes is unknown. We aimed to assess whether supplementation with vitamins C and E reduced incidence of pre-eclampsia in women with type 1 diabetes.

Methods
We enrolled women from 25 UK antenatal metabolic clinics in a multicentre randomised placebo-controlled trial. Eligibility criteria were type 1 diabetes preceding pregnancy, presentation between 8 weeks’ and 22 weeks’ gestation, singleton pregnancy, and age 16 years or older. Women were randomly allocated in a 1:1 ratio to receive1000 mg vitamin C and 400 IU vitamin E (a-tocopherol) or matched placebo daily until delivery. The randomisation sequence was stratifi ed by centre with balanced blocks of eight patients. All trial personnel and participants were masked to treatment allocation. The primary endpoint was pre-eclampsia, which we defi ned as gestational hypertension with proteinuria. Analysis was by modifi ed intention to treat. This study is registered, ISRCTN27214045.

Findings
Between April, 2003, and June, 2008, 762 women were randomly allocated to treatment groups (379 vitamin supplementation, 383 placebo). The primary endpoint was assessed for 375 women allocated to receive vitamins, and 374 allocated to placebo. Rates of pre-eclampsia did not differ between vitamin (15%, n=57) and placebo (19%, 70)groups (risk ratio 0·81, 95% CI 0·59–1·12). No adverse maternal or neonatal outcomes were reported.

Interpretation
Supplementation with vitamins C and E did not reduce risk of pre-eclampsia in women with type 1 diabetes. However, the possibility that vitamin supplementation might be benefi cial in women with a low antioxidant status at baseline needs further testing.

Chromospheric velocities of a C-class flare

Aims. We use high spatial and temporal resolution observations from the Swedish Solar Telescope to study the chromospheric velocities of a C-class flare originating from active region NOAA 10969.
Methods. A time-distance analysis is employed to estimate directional velocity components in Hα and Ca ii K image sequences. Also, imaging spectroscopy has allowed us to determine flare-induced line-of-sight velocities. A wavelet analysis is used to analyse the periodic nature of associated flare bursts.
Results. Time-distance analysis reveals velocities as high as 64 km s-1 along the flare ribbon and 15 km s-1 perpendicular to it. The velocities are very similar in both the Hα and Ca ii K time series. Line-of-sight Hα velocities are red-shifted with values up to 17 km s-1. The high spatial and temporal resolution of the observations have allowed us to detect velocities significantly higher than those found in earlier studies. Flare bursts with a periodicity of ≈60 s are also detected. These bursts are similar to the quasi-periodic oscillations observed at hard X-ray and radio wavelength data.
Conclusions. Some of the highest velocities detected in the solar atmosphere are presented. Line-of-sight velocity maps show considerable mixing of both the magnitude and direction of velocities along the flare path. A change in direction of the velocities at the flare kernel has also been detected which may be a signature of chromospheric evaporation.

Evaluation of c-FLIP in castrate-resistant prostate cancer antagonizes therapeutic response to androgen receptor-targeted therapy

Purpose: To characterize the importance of cellular Fas-associated death domain (FADD)–like interleukin 1ß-converting enzyme (FLICE) inhibitory protein (c-FLIP), a key regulator of caspase-8 (FLICE)–promoted apoptosis, in modulating the response of prostate cancer cells to androgen receptor (AR)–targeted therapy.

Experimental Design: c-FLIP expression was characterized by immunohistochemical analysis of prostatectomy tissue. The functional importance of c-FLIP to survival and modulating response to bicalutamide was studied by molecular and pharmacologic interventions.

Results: c-FLIP expression was increased in high-grade prostatic intraepithelial neoplasia and prostate cancer tissue relative to normal prostate epithelium (P < 0.001). Maximal c-FLIP expression was detected in castrate-resistant prostate cancer (CRPC; P < 0.001). In vitro, silencing of c-FLIP induced spontaneous apoptosis and increased 22Rv1 and LNCaP cell sensitivity to bicalutamide, determined by flow cytometry, PARP cleavage, and caspase activity assays. The histone deacetylase inhibitors (HDACi), droxinostat and SAHA, also downregulated c-FLIP expression, induced caspase-8- and caspase-3/7–mediated apoptosis, and increased apoptosis in bicalutamide-treated cells. Conversely, the elevated expression of c-FLIP detected in the CRPC cell line VCaP underpinned their insensitivity to bicalutamide and SAHA in vitro. However, knockdown of c-FLIP induced spontaneous apoptosis in VCaP cells, indicating its relevance to cell survival and therapeutic resistance.

Conclusion: c-FLIP reduces the efficacy of AR-targeted therapy and maintains the viability of prostate cancer cells. A combination of HDACi with androgen deprivation therapy may be effective in early-stage disease, using c-FLIP expression as a predictive biomarker of sensitivity. Direct targeting of c-FLIP, however, may be relevant to enhance the response of existing and novel therapeutics in CRPC. Clin Cancer Res; 18(14); 3822–33.

Automatic FPGA Synthesis of Memory Intensive C-based Kernels

Realising high performance image and signal processing
applications on modern FPGA presents a challenging implementation problem due to the large data frames streaming through these systems. Specifically, to meet the high bandwidth and data storage demands of these applications, complex hierarchical memory architectures must be manually specified
at the Register Transfer Level (RTL). Automated approaches which convert high-level operation descriptions, for instance in the form of C programs, to an FPGA architecture, are unable to automatically realise such architectures. This paper
presents a solution to this problem. It presents a compiler to automatically derive such memory architectures from a C program. By transforming the input C program to a unique dataflow modelling dialect, known as Valved Dataflow (VDF), a mapping and synthesis approach developed for this dialect can
be exploited to automatically create high performance image and video processing architectures. Memory intensive C kernels for Motion Estimation (CIF Frames at 30 fps), Matrix Multiplication (128x128 @ 500 iter/sec) and Sobel Edge Detection (720p @ 30 fps), which are unrealisable by current state-of-the-art C-based synthesis tools, are automatically derived from a C description of the algorithm.

Hypercyclic tuples of operators on $C^n$ and $R^n$

A tuple $(T_1,\dots,T_n)$ of continuous linear operators on a topological vector space $X$ is called hypercyclic if there is $x\in X$ such that the the orbit of $x$ under the action of the semigroup generated by $T_1,\dots,T_n$ is dense in $X$. This concept was introduced by N.~Feldman, who have raised 7 questions on hypercyclic tuples. We answer those 4 of them, which can be dealt with on the level of operators on finite dimensional spaces. In
particular, we prove that the minimal cardinality of a hypercyclic tuple of operators on $\C^n$ (respectively, on $\R^n$) is $n+1$ (respectively, $\frac n2+\frac{5+(-1)^n}{4}$), that there are non-diagonalizable tuples of operators on $\R^2$ which possess an orbit being neither dense nor nowhere dense and construct a hypercyclic 6-tuple of operators on $\C^3$ such that every operator commuting with each member of the tuple is non-cyclic.