A 330-360 GHz spectral survey of G 34.3+0.15 .1. Data and physical analysis

A 330--360 GHz spectral survey of the hot molecular core associated with the 'cometary' ultracompact HII region G 34.3+/-0.15 observed with the James Clerk Maxwell Telescope has detected 338 spectral lines from at least 35 distinct chemical species plus 19 isotopomers. 70 lines remain unidentified. Chemical abundance and rotation temperature have been determined by rotation diagram analysis for 12 species, and lower limits to abundance found for 38 others.

Vaughan Williams and contemporary music: composers' forum

Like many long-lived composers, Vaughan Williams suffered a decline in his reputation immediately following his death, as the emergence in the 1960s of a younger generation of composers rendered much of his work outmoded in the eyes of many critics. In recent years, however, the reception of Vaughan Williams's music among composers has improved markedly, a combination of the ebbing of the tide of high modernism and greater pluralism in contemporary music, and a growing awareness that Vaughan Williams was perhaps more modernist (or at least progressive) than had previously been thought. In interviews with four leading British composers (two of whom were part of the 1960s generation mentioned above), I investigate the nature and extent of Vaughan Williams's legacy to his successors, both musical and social. What emerges is a near consensus on Vaughan Williams's greatest works, but a diversity of views on his compositional techniques and on his place among his European contemporaries.

Rotman lens based-retrodirective array

A new type of broadband retrodirective array, which has been constructed using a microstrip Rotman lens, is presented. Automatic tracking of targets is obtained by exploiting the conjugate phase response of the beamforming network which is exhibited when the input ports are terminated with either open or short circuits. In addition, the true time-delay property of the Rotman lens gives broadband operation of the self-tracking array when used in conjunction with Vivaldi antennas. The simulated and measured bistatic and monostatic radar cross-section (RCS) patterns of a structure consisting of 13 beamports and 12 array ports are presented at frequencies in the range 8-12 GHz. Significantly enhanced RCS within the scan coverage ±40° is demonstrated by comparing the retrodirective behavior of a 12-element Vivaldi array terminated with and without the Rotman lens. © 2006 IEEE.

IR laser desorption of oligonucleotides A novel gas phase target for radiation damage studies

The desorption of oligonucleotides by 3 mu m laser irradiation has been studied by laser induced fluorescence imaging of the resulting gas phase plumes. Fitting of the plume data has been achieved by using a modified Maxwell Boltzmann distribution which incorporates a range of stream velocities. Spatial density profiles, velocities and temperature variation have been determined from these fits indicating that the oligonucleotide plume only achieves a partial thermal relaxation. This laser desorption technique may provide a means of overcoming the limited mass range of gas phase biomolecules available from thermal evaporation techniques.

Sequence characterisation and expression of homeobox HOX A7 in the multi-potential erythroleukaemic cell line TF-1

Homeobox gene expression was examined in the erythroleukaemic cell line TF-1. Expression of a number of HOX A, B and C genes, including HOX A7 was detected. Expression of this gene has not previously been reported in erythroleukaemic cell lines. A 2.1 kb full length cDNA of the HOX A7 gene was cloned. The predicted amino acid sequence C-terminal to the homeodomain consists of an alanine-rich region and a strongly negatively charged domain consisting entirely of aspartic and glutamic acid residues.

Association of MYH9/APOL1 with chronic kidney disease in a UK population

Following the first report on the association between MYH9 gene variants and glomerular disorders [1], many studies have evaluated MYH9 loci for association with a range of kidney diseases [2]. In 2010, functional mutations in the adjacent APOL1 gene were identified as the primary variants responsible for associations with kidney disease that had previously been attributed to the MHY9 gene [3]. Nevertheless, several loci within MHY9 continue to be independently reported as risk factors for chronic kidney disease (CKD) [2, 4].

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.

SNP in the genome-wide association study hotspot on chromosome 9p21 confers susceptibility to diabetic nephropathy in type 1 diabetes

AIMS/HYPOTHESIS: Parental type 2 diabetes mellitus increases the risk of diabetic nephropathy in offspring with type 1 diabetes mellitus. Several single nucleotide polymorphisms (SNPs) that predispose to type 2 diabetes mellitus have recently been identified. It is, however, not known whether such SNPs also confer susceptibility to diabetic nephropathy in patients with type 1 diabetes mellitus. METHODS: We genotyped nine SNPs associated with type 2 diabetes mellitus in genome-wide association studies in the Finnish population, and tested for their association with diabetic nephropathy as well as with severe retinopathy and cardiovascular disease in 2,963 patients with type 1 diabetes mellitus. Replication of significant SNPs was sought in 2,980 patients from three other cohorts. RESULTS: In the discovery cohort, rs10811661 near gene CDKN2A/B was associated with diabetic nephropathy. The association remained after robust Bonferroni correction for the total number of tests performed in this study (OR 1.33 [95% CI 1.14, 1.56], p?=?0.00045, p (36tests)?=?0.016). In the meta-analysis, the combined result for diabetic nephropathy was significant, with a fixed effects p value of 0.011 (OR 1.15 [95% CI 1.02, 1.29]). The association was particularly strong when patients with end-stage renal disease were compared with controls (OR 1.35 [95% CI 1.13, 1.60], p?=?0.00038). The same SNP was also associated with severe retinopathy (OR 1.37 [95% CI 1.10, 1.69] p?=?0.0040), but the association did not remain after Bonferroni correction (p (36tests)?=?0.14). None of the other selected SNPs was associated with nephropathy, severe retinopathy or cardiovascular disease. CONCLUSIONS/INTERPRETATION: A SNP predisposing to type 2 diabetes mellitus, rs10811661 near CDKN2A/B, is associated with diabetic nephropathy in patients with type 1 diabetes mellitus.