N-terminally modified glucagon-like peptide-1(7-36) amide exhibits resistance to enzymatic degradation while maintaining its antihyperglycaemic activity in vivo

Glucagon-like peptide-1 (7-36)amide (tGLP-1) is inactivated by dipeptidyl peptidase (DPP) IV by removal of the NH2-terminal dipeptide His(7)-Ala(8). We examined the degradation of NH2-terminally modified His(7)-glucitol tGLP-1 and its insulin-releasing and antihyperglycaemic activity in vivo, tGLP-1 was degraded by purified DPP IV after 4 h (43% intact) and after 12 hi 89% was converted to GLP-1(9-36)amide. In contrast > 99% of His(7)-glucitol tGLP-1 remained intact at 12 h. His(7)-glucitol tGLP-1 was similarly resistant to plasma degradation in vitro. His7-glucitol tGLP-1 showed greater resistance to degradation in vivo (92% intact) compared to tGLP-1 (27% intact) 10 min after i.p. administration to Wistar rats. Glucose homeostasis was examined following i.p. injection of both peptides (12 nmol/kg) together with glucose (18 mmol/kg). Plasma glucose concentrations were significantly reduced and insulin concentrations elevated following peptides administration compared with glucose alone. The area under the curve (AUC) for glucose for controls (AUC 691 +/- 35 mM/min) was significantly lower after administration of tGLP-1 and His7-glucitol tGLP-1 (36 and 49% less; AUC; 440 +/- 40 and 353 +/- 31 mM/min, respectively; P

Autobiography and Invention: Towards a Critical Understanding of Identity, Dialogue and Resistance in Improvised Musics

In this article I will argue that acts of improvisation are not productively understood in opposition to other practices which form our wider musical culture. Improvisation might be better understood as both rooted in, but not limited by, personal and cultural memory. Improvisational activities are legible to the performer and audience through a shared understanding of social norms, but only become a singular instance of improvisation through unique performative actions. This tension between experience and invention is played out in a dialogue between performer and listener, demanding a response that crucially takes the form of self-articulation, or autobiography. Finally, I contend that it is from this position that improvisation offers the possibility to transgress established personal and cultural identities.

Micro-Raman and Spreading Resistance Analysis on Beveled Implanted Germanium for Layer Transfer Applications

Raman and spreading resistance profiling have been used to analyze defects in germanium caused by hydrogen and helium implants, of typical fluences used in layer transfer applications. Beveling has been used to facilitate probing beyond the laser penetration depth. Results of Raman mapping along the projection area reveal that after post-implant annealing at 400°C, some crystal damage remains, while at 600°C, the crystal damage has been repaired. Helium implants create acceptor states beyond the projected range, and for both hydrogen and helium, 1×1016 acceptors/cm2 remain after 600°C. These are thought to be vacancy-related point defect clusters.

Low cytosine triphosphate synthase 2 expression renders resistance to 5-fluorouracil in colorectal cancer

Understanding the determinants of resistance of 5-fluorouracil (5FU) is of significant value to optimizing administration of the drug, and introducing novel agents and treatment strategies. Here, the expression of 92 genes involved in 5FU transport, metabolism, co-factor (folate) metabolism and downstream effects was measured by real-time PCR low density arrays in 14 patient-derived colorectal cancer xenografts characterized for 5FU resistance. Candidate gene function was tested by siRNA and uridine modulation, and immunoblotting, apoptosis and cell cycle analysis. Predictive significance was tested by immunohistochemistry of tumors from 125 stage III colorectal cancer patients treated with and without 5FU. Of 8 genes significantly differentially expressed between 5FU sensitive and resistant xenograft tumors, CTPS2 was the gene with the highest probability of differential expression (p = 0.008). Reduction of CTPS2 expression by siRNA increased the resistance of colorectal cancer cell lines DLD1 and LS174T to 5FU and its analog, FUDR. CTPS2 siRNA significantly reduced cell S-phase accumulation and apoptosis following 5FU treatment. Exposure of cells to uridine, a precursor to the CTPS2 substrate uridine triphosphate, also increased 5FU resistance. Patients with low CTPS2 did not gain a survival benefit from 5FU treatment (p = 0.072), while those with high expression did (p = 0.003). Low CTPS2 expression may be a rationally-based determinant of 5FU resistance.

Investigation of a ship's propeller jet using momentum decay and energy decay

Previous researchers use the velocity decay as an input to investigate the ship’s propeller jet induced scour. A researcher indicated that most of the equations used to predict the stability of various protection systems are often missing a physical background. The momentum decay and energy decay are currently proposed as an initial input for seabed scouring investigation, which are more sensible in physics. Computational fluid dynamics (CFD) and laser Doppler anemometry (LDA) experiments are used to obtain the velocity data and then transforming into momentum and energy decays. The findings proposed several exponential equations of velocity, momentum and energy decays to estimate the region exposed to the seabed scouring.

Structure-Based Mutational Analysis of eIF4E in Relation to sbm1 Resistance to Pea Seed-Borne Mosaic Virus in Pea

Background: Pea encodes eukaryotic translation initiation factor eIF4E (eIF4E(S)), which supports the multiplication of Pea seed-borne mosaic virus (PSbMV). In common with hosts for other potyviruses, some pea lines contain a recessive allele (sbm1) encoding a mutant eIF4E (eIF4E(R)) that fails to interact functionally with the PSbMV avirulence protein, VPg, giving genetic resistance to infection.

Molecular characterization and phylogenetic analysis of quinolone resistance-determining regions (QRDRs) of gyrA, gyrB, parC and parE gene loci in viridans group streptococci isolated from adult patients with cystic fibrosis

This study demonstrated key resistance genes to fluroquinilones in Streptococcci isolated from sputum of people with CF. This suggests that other bacteria which are sometimes considered commensal may be a resovoir for resistance. Jse designed the study with Moore.

Abrasive wear resistance of electroless Ni-P coated aluminium after post treatment

Electroless nickel (EN) coatings are recognised for their hardness and wear resistance in automotive and aerospace industries. In this work, electroless Ni–P coatings were deposited on aluminium alloy substrate LM24 (Al–9 wt.% Si alloy) and the effect of post treatment on the wear resistance was studied. The post treatments included heat treatment and lapping with two different surface textures. Scanning electron microscopy (SEM), energy dispersive spectrometry (EDS), X-ray diffraction (XRD) and micro-abrasion tester were used to analyse morphology, structure and abrasive wear resistance of the coatings. Post heat treatment significantly improved the coating density and structure, giving rise to enhanced hardness and wear resistance. Microhardness of electroless Ni–P coatings with thickness of about 15 μm increased due to the formation of Ni3P after heat treatment.

How the ship of fools was ship-wrecked - The Irish crisis and response

For a decade and half the Irish economy was the poster-boy of Europe. With substantial growth rates, an open economy, flexible labour markets and low levels of taxation, Ireland was seen as evidence of the success of neoliberal policies. Yet in the matter of a few short years Ireland has turned into a one of the peripheral black-holes (along with Greece and Portugal) that are threatening to bring down the whole Eurozone project. Given this context the paper will address two key questions. Firstly how did the much eulogised Celtic Tiger fall so far and so fast? And, secondly, what has been the government’s response to the fall and crash of the Irish economy? These two questions will be addressed through both a general historical analysis of the developments of Irish society up to the crash in 2008 and then the responses to it. Secondly by an analysis of two specific elements of that development; namely the much discussed low corporation tax rate and the failure of social housing to deliver decent affordable homes for those at the bottom of society. The third element is a review of the banking and sovereign debt crisis that led to the IMF/EU deal in November 2010 and a brief outlining of its implications for public finances, especially the question of default. The paper concludes by placing the Irish crisis in a global context.