Characterisation of the cold metal transfer (CMT) process and its application for low dilution cladding

The process characteristics of the synergic cold metal transfer (CMT) process have been examined for welding aluminium alloy. Utilising a simple backlighting system and through the arc monitoring the droplet transfer modes were identified. Whilst the modified short circuit mode was evident for the lower parameter range, a two part transfer mode based upon a combination of spray and short circuit transfer was observed for the mid to upper parameter range. The technology was also explored as a cladding process for applying to ternary alloyed (Al–Cu–Mg) aluminium plate. This alloy system is known to be susceptible to solidification cracking when MIG welded using the binary Al-2319 (Al–Cu) filler wire, this being due to the wide element freezing range of the weld resulting from mixing with the base material. Utilising this filler, weld dilution ratios for both CMT and pulsed welding were identified across the examined parameter range. The CMT process exhibited greater control of dilution that enabled deposition of a quasi-binary (Al–Cu) layer exhibiting a less crack susceptible composition. Onto this layer conventional MIG welding could be applied which could potentially eradicate cracking using a binary fi

Olefin strain energy as a predictor of isolability

Data collection contains:Determination of the olefin stratin energy ranges corresponding to isolable, observable and unstable alkenes with contemporary forcefields - Bridgehead alkenes used to determine the olefin strain energy ranges corresponding to isolable, observable, and unstable  alkenes;Forcefield energies of alkenes S1-S25 and alkanes S1H2-S25H2;Olefin strain energies of alkenes S1-S25;Olefin strain energies of alkenes S1-S25 computed with different forcefields;Olefin strain energies of alkenes S1-S19 computed with different force fields, plotted against MM1 OS energy;Olefin strain energy calculations for natural products -Forcefield energies or bridgehead alkene natural products or putative bridgehead alkene natural products, and the  corresponding alkanes;Olefin strain energies of bridgehead alkene natural products or putative alkene natural products;OPLS_2005 Optimized geometries;Density Functional Theory (DFT) calculations -DFT calculations on NP's giving a measure of the amount of strain energy not captured by the forcefield;B3LYP-D3 optimized geometries and associated energies;A small set of alkenes for rapid estimation of OS cutoffs for other forcefield

Time-resolved velocity map imaging of methyl elimination from photoexcited anisole

To date, H-atom elimination from heteroaromatic molecules following UV excitation has been extensively studied, with the focus on key biological molecules such as chromophores of DNA bases and amino acids. Extending these studies to look at elimination of other non-hydride photoproducts is essential in creating a more complete picture of the photochemistry of these biomolecules in the gas-phase. To this effect, CH3 elimination in anisole has been studied using time resolved velocity map imaging (TR-VMI) for the first time, providing both time and energy information on the dynamics following photoexcitation at 200 nm. The extra dimension of energy afforded by these measurements has enabled us to address the role of πσ* states in the excited state dynamics of anisole as compared to the hydride counterpart (phenol), providing strong evidence to suggest that only CH3 fragments eliminated with high kinetic energy are due to direct dissociation involving a 1πσ* state. These measurements also suggest that indirect mechanisms such as statistical unimolecular decay could be contributing to the dynamics at much longer times

Pharmaceuticals that contain polycyclic hydrocarbon scaffolds

Numerous variations on structural motifs exist within pharmaceutical compounds that have entered the clinic. These variations have amounted over many decades based on years of drug development associated with screening natural products and de novo synthetic systems. Caged (or bridged) bicyclic structural elements offer a variety of diverse features, encompassing three-dimensional shape, and assorted pharmacokinetic properties. This review highlights approximately 20 all carbon cage containing pharmaceuticals, ranging in structure from bicyclo[2.2.1] through to adamantane, including some in the top-selling pharmaceutical bracket. Although, a wide variety of human diseases, illnesses and conditions are treated with drugs containing the bicyclic motif, a common feature is that many of these lipophilic systems display CNS and/or neurological activity. In addition, to an extensive overview of the history and biology associated with each drug, a survey of synthetic methods used to construct these entities is presented. An analysis section compares natural products to synthetics in drug discovery, and entertains the classical caged hydrocarbon systems potentially missing from the clinic. Lastly, this unprecedented review is highly pertinent at a time when big pharma is desperately trying to escape flatland drugs

Human mouthfeel panel investigating the acceptability of electrospun and solvent cast orodispersible films

A human panel study was performed to investigate the acceptability of orodispersible electrospun and solvent cast films. 50 healthy volunteers took two drug-free samples of polyvinyl alcohol films prepared by the two methods. On a 5-point hedonic scale, the volunteers assessed the films’ perceived size, stickiness, thickness, disintegration time, thickening effect on saliva, and handling. The films manufactured by both methods were similar in their end-user acceptability. The modal values of perceived size, thickness, disintegration time, saliva thickening effect, and handling were high (4 or 5). However, for both, the stickiness mode was 2 (strongly sticky) and the only negative attribute. Both films were reported to take approximately 30 s to disintegrate completely in the mouth. Electrospun films scored similarly high to solvent cast orodispersible films in most attributes of end-user acceptability. Electrospun films were marginally preferred, with 27 out of 50 participants picking electrospinning when presented with a forced choice test of both fabrication methods. This is the first study to show that electrospinning enables the fabrication of orodispersible films that are acceptable to adult human participants in terms of handling and mouthfeel and suggests that the potential for clinical translation of such formulations is high

A Prospective Surveillance Study of Candidaemia : Epidemiology, Risk Factors, Antifungal Treatment and Outcome in Hospitalized Patients

Funding This work was supported by the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377/Z/11/Z. Data collection was supported by a grant from Pfizer. GR was also supported by a research fellowship grant from Gilead Sciences. The collection of the isolates was funded by a Gilead Fellowship to GR. Acknowledgments We are grateful to microbiology colleagues throughout Scotland for submitting isolates. Antimicrobial sensitivity testing was performed by the Mycology Reference Laboratory, Public Health England, Bristol.Peer reviewedPublisher PD

Increased prevalence of precancerous changes in relatives of gastric cancer patients: critical role of H. pylori

Background & Aims:Helicobacter pylori is believed to predispose to gastric cancer by inducing gastric atrophy and hypochlorhydria. First-degree relatives of patients with gastric cancer have an increased risk of developing gastric cancer. The aim of this study was to determine the prevalence of atrophy and hypochlorhydria and their association with H. pylori infection in first-degree relatives of patients with gastric cancer. Methods:H. pylori status, gastric secretory function, and gastric histology were studied in 100 first-degree relatives of patients with noncardia gastric cancer and compared with those of controls with no family history of this cancer. Results: Compared with healthy controls, relatives of patients with gastric cancer had a higher prevalence of hypochlorhydria (27% vs. 3%) but a similar prevalence of H. pylori infection (63% vs. 64%). Relatives of cancer patients also had a higher prevalence of atrophy (34%) than patients with nonulcer dyspepsia (5%) matched for H. pylori prevalence. Among the relatives of cancer patients, the prevalence of atrophy and hypochlorhydria was increased only in those with evidence of H. pylori infection, was greater in relatives of patients with familial cancer than in relatives of sporadic cancer index patients, and increased with age. Eradication of H. pylori infection produced resolution of the gastric inflammation in each subject and resolution of hypochlorhydria and atrophy in 50% of the subjects. Conclusions: Relatives of patients with gastric cancer have an increased prevalence of precancerous gastric abnormalities, but this increase is confined to those with H. pylori infection. Consequently, prophylactic eradication of the infection should be offered to such subjects