Investigating direct routes to an advanced intermediate for the synthesis of C-20 diterpene alkaloids

Rapid access to the ABCE ring system of the C-20 diterpene alkaloids was achieved by silver (I) promoted intramolecular Friedel-Crafts arylation of a functional group specific 5-bromo-3-azabicyclo[3.3.1]nonane derivative. (c) 2005 Elsevier Ltd. All rights reserved.

Identifying health centers in Honduras infested with Rhodnius prolixus using the seroprevalence of Chagas disease in children younger than 13 years

The objective of this study is to determine if a Chagas disease protocol starting with a serological survey is as reliable at identifying insect-infested areas as one using the gold standard entomological survey. The study found that health center areas infested with Rhodnius prolixus were identified using a threshold seroprevalence of 0.1%. The serological survey took half the time and was 30% less expensive than the entomological survey. Developing countries with limited resources may find this strategy useful in combating Chagas disease. This strategy also identifies seropositive children, which facilitates their treatment.

Pyrrolizidine alkaloids in Senecio madagascariensis from Australia and Hawaii and assessment of possible livestock poisoning

The alkaloid content of Senecio madagascariensis collected from Australia and Hawaii was examined. Alkaloids were identified from the above ground whole plant (stems, leaves and flowers) by GUMS analysis and included: senecivernine, senecionine, integerrimine, senkirkine, mucronatinine, retrosine, usaramine, otosenine, acetylsenkirkine, desacetyldoronine, florosenine and doronine. Plant material collected from the Hawaiian Islands was found to be identical in pyrrolizidine alkaloid content to that from a single composite collection made from northern New South Wales, Australia. Overall, no appreciable differences in alkaloid content were found between locations, whereas variation among individual plants was evident. The average total pyrrolizidine alkaloid content varied from a low of 217 mu g/g to a high of 1990 mu g/g (dry weight basis) among the locations. Based on comparable alkaloid content and documented pyrrolizidine alkaloidosis cases from Australia, S. madagascariensis may pose a significant risk to livestock grazing heavily infested ranges on the Hawaiian Islands. (c) 2006 Elsevier Ltd. All rights reserved.

A Cochrane review (update 2004): Hylan G-F 20 vs placebo for knee OA

Aim of study: As part of a Cochrane review of viscosupplementation in knee OA, randomised controlled trials (RCT) were reviewed to evaluate evidence for the efficacy of viscosupplementation with Hylan G-F 20 compared to placebo. Methods: Electronic searches were conducted of MEDLINE, EMBASE, Premedline, Current Contents, and CENTRAL. Human, RCT involving Hylan G-F 20 compared to placebo, published prior to 1Q2004, were included. Trials were selected and data extracted by two independent reviewers. Methodological quality was assessed with the Jadad criteria by two reviewers. Data on the OARSI and OMERACT core set clinical outcome measures were extracted where possible. Weighted mean difference (WMD), based on post-test scores, and 95% confidence intervals (CI) were calculated for continuous outcome measures and relative risk (RR) for dichotomous outcome measures. Results: Seven RCT met the inclusion criteria. Median methodological quality was 4 (range 1–5). A further two studies were only reported in abstract form (Jadad score Z 1) and contained insufficient extractable data for inclusion in the analysis. Nine RCT, which compared Hylan G-F 20 to other interventions such as intra-articular corticosteroid, physiotherapy, NSAID, appropriate care, intra-articular gaseous oxygen and other hyaluronan, are not reported here. Twenty-three studies failed to meet inclusion criteria and were excluded. Hylan G-F 20 was more efficacious than placebo at 1–4 weeks post-injection for pain on weight-bearing WMD (random effects [RE]) 13 mm on a 0–100 mm VAS (P Z 0.002) based on 6 RCT. This difference was even greater at 5–13 weeks post-injection, 22 m (RE) (P Z 0.001) based on 5 RCT, and at 14–6 weeks postinjection, 21 m (RE) (P Z 0.006) based on 4 RCT. Hylan G-F 20 was more efficacious than placebo at 1–4 weeks post-injection for pain at night, WMD 7 mm on a 0–100 mm VAS (P Z 0.003) based on 5 RCT. This difference was even greater at 5–13 weeks post-injection, 11 mm (P Z 0.008) based on 4 RCT, and at 14–26 weeks post-injection, 17 mm (P ! 0.00001) based on 3 RCT. There was no significant difference (WMD 8 mm) between Hylan G-F 20 C oral placebo and arthrocentesis C oral placebo at 5–13 weeks post-injection for WOMAC Pain, but Hylan G-F 20 C oral placebo was more efficacious than arthrocentesis C oral placebo for WOMAC Function, WMD 9 mm on a 0–100 mm VAS (P Z 0.01) (Dickson, 2001). Hylan G-F 20 was more effective than placebo at 1–4 weeks postinjection for the variable designed treatment efficacy, WMD 22 mm on a 0–100 mm VAS (P ! 0.00001) based on improvement in 4 RCT. This difference was even greater at 5–13 weeks post injection, 35 mm (P ! 0.00001). Conclusions: Evidence from this updated Cochrane review supports the superior efficacy of Hylan G-F 20 compared to placebo on weight-bearing pain, night pain, function and treatment efficacy in the treatment of knee OA.

Central and peripheral mediation of human force sensation following eccentric or concentric contractions

Fatigue was induced in the triceps brachii of the experimental arm by a regimen of either eccentric or concentric muscle actions. Estimates of force were assessed using a contralateral limb-matching procedure, in which target force levels (25 %, 50 % or 75 % of maximum) were defined by the unfatigued control arm. Maximum isometric force-generating capacity was reduced by 31 % immediately following eccentric contractions, and remained depressed at 24 (25 %) and 48 h (13 %) post-exercise. A less marked reduction (8.3 %) was observed immediately following concentric contractions. Those participants who performed prior eccentric contractions, consistently (at all force levels), and persistently (throughout the recovery period), overestimated the level of force applied by the experimental arm. In other words, they believed that they were generating more force than they actually achieved. When the forces applied by the experimental and the control arm, were each expressed as a proportion of the maximum force that could be attained at that time, the estimates matched extremely closely. This outcome is that which would be expected if the estimates of force were based on a sense of effort. Following eccentric exercise, the amplitude of the EMG activity recorded from the experimental arm was substantially greater than that recorded from the control arm. Cortically evoked potentials recorded from the triceps brachii (and extensor carpi radialis) of the experimental arm were also substantially larger than those elicited prior to exercise. The sense of effort was evidently not based upon a corollary of the central motor command. Rather, the relationship between the sense of effort and the motor command appears to have been altered as a result of the fatiguing eccentric contractions. It is proposed that the sense of effort is associated with activity in neural centres upstream of the motor cortex.

Integrability of the Russian doll BCS model

We show that integrability of the BCS model extends beyond Richardson's model (where all Cooper pair scatterings have equal coupling) to that of the Russian doll BCS model for which the couplings have a particular phase dependence that breaks time-reversal symmetry. This model is shown to be integrable using the quantum inverse scattering method, and the exact solution is obtained by means of the algebraic Bethe ansatz. The inverse problem of expressing local operators in terms of the global operators of the monodromy matrix is solved. This result is used to find a determinant formulation of a correlation function for fluctuations in the Cooper pair occupation numbers. These results are used to undertake exact numerical analysis for small systems at half-filling.

Subject/Object Asymmetry in the Comprehension of English Relative Clauses by Japanese Learners of English

While a number of studies have shown that object-extracted relative clauses are more difficult to understand than subject-extracted counterparts for second language (L2) English learners (e.g., Izumi, 2003), less is known about why this is the case and how they process these complex sentences. This exploratory study examines the potential applicability of Gibson's (1998, 2000) Syntactic Prediction Locality Theory (SPLT), a theory proposed to predict first language (L1) processing difficulty, to L2 processing and considers whether the theory might also account for the processing difficulties of subject- and object-extracted relative clauses encountered by L2 learners. Results of a self-paced reading time experiment from 15 Japanese learners of English are mainly consistent with the reading time profile predicted by the SPLT and thus suggest that the L1 processing theory might also be able to account for L2 processing difficulty.

User guide for shock and blast simulation with the OctVCE code (version 3.5+), Department of Mechanical Engineering Report 2007/13

OctVCE is a cartesian cell CFD code produced especially for numerical simulations of shock and blast wave interactions with complex geometries. Virtual Cell Embedding (VCE) was chosen as its cartesian cell kernel as it is simple to code and sufficient for practical engineering design problems. This also makes the code much more ‘user-friendly’ than structured grid approaches as the gridding process is done automatically. The CFD methodology relies on a finite-volume formulation of the unsteady Euler equations and is solved using a standard explicit Godonov (MUSCL) scheme. Both octree-based adaptive mesh refinement and shared-memory parallel processing capability have also been incorporated. For further details on the theory behind the code, see the companion report 2007/12.

NMR study of the radiation-induced cross-linking of poly(tetrafluoroethylene-co-perfluoromethyl vinyl ether)

The gamma-radiolysis of poly(tetrafluoroethylene-co-perfuoromethyl vinyl ether) (TFE/PMVE) was investigated using solid state F-19 and C-13 NMR spectroscopy. Chain scission products identified in the polymer were saturated chain ends -CF2CF3 (G = 1.0), methyl ether end groups -CF2OCF3 (G = 0.9), acid end groups -CF2COOH (G = 0.5), and a small amount of terminal unsaturation -CF=CF2 (G = 0.2). A mechanism for the formation of these scission products was proposed and the G value for main chain scission, G(S), was determined to be 1.4. Cross-linking of TFE/PMVE was found to proceed via a Y-linking mechanism. The G value for cross-linking, G(X), was determined to be 0.9. A maximum of 0.2 mol % cross-links were formed under the experimental conditions.

The crosslinking mechanism in gamma irradiation of polyarylsulfone: Evidence for Y-links

Measurements of molecular weights, soluble fractions and examination of NMR spectra of bisphenol-A polysulfone, after gamma irradiation in vacuum at 150 degrees C were used to elucidate the mechanism of crosslinking. Excellent agreement was obtained between G(S) and G(X) determined from measurements above and below the gel dose when a Y-linking mechanism was assumed, whereas poor agreement was obtained when an H-link mechanism was assumed, which is the mechanism normally believed to be responsible for crosslinking. New resonances were observed in the C-13 NMX spectra of the irradiated polymer which were consistent with the formation of Y-links involving phenylene units in the backbone chain. (C) 1998 John Wiley & Sons, Ltd.

MHCPEP, a database of MHC-binding peptides: update 1997

MHCPEP (http://wehih.wehi.edu.au/mhcpep/) is a curated database comprising over 13 000 peptide sequences known to bind MHC molecules, Entries are compiled from published reports as well as from direct submissions of experimental data, Each entry contains the peptide sequence, its MHC specificity and where available, experimental method, observed activity, binding affinity, source protein and anchor positions, as well as publication references, The present format of the database allows text string matching searches but can easily be converted for use in conjunction with sequence analysis packages. The database can be accessed via Internet using WWW or FTP.

Functional polymorphism of the human arylamine N-acetyltransferase type 1 gene caused by (CT)-T-190 and G(560)A mutations

Human N-acetyltransferase type 1 (NAT1) catalyses the N- or O-acetylation of various arylamine and heterocyclic amine substrates and is able to bioactivate several known carcinogens. Despite wide inter-individual variability in activity, historically, NAT1 was considered to be monomorphic in nature. However, recent reports of allelic variation at the NAT1 locus suggest that it may be a polymorphically expressed enzyme. In the present study, peripheral blood mononuclear cell NAT1 activity in 85 individuals was found to be bimodally distributed with approximately 8% of the population being slow acetylators. Subsequent sequencing of the individuals having slow acetylator status showed all to have either a (CT)-T-190 or G(560)A base substitution located in the protein encoding region of the NAT1 gene. The (CT)-T-190 base substitution changed a highly conserved Arg(64), which others have shown to be essential for fully functional NAT1 protein. The (CT)-T-190 mutation has not been reported previously and we have named it NAT1*17. The G(560)A mutation is associated with the base substitutions previously observed in the NAT1*10 allele and this variant (NAT1*14) encodes for a protein with reduced acetylation capacity. A novel method using linear PCR and dideoxy terminators was developed for the detection of NAT1*14 and NAT1*17. Neither of these variants was found in the rapid acetylator population. We conclude that both the (CT)-T-190 (NAT1*17) and G(560)A (NAT1*14) NAT1 structural variants are involved in a distinct NAT1 polymorphism. Because NAT1 can bioactivate several carcinogens, this polymorphism may have implications for cancer risk in individual subjects. (C) 1998 Chapman & Hall Ltd.