Magnetic Field Patterning of Nickel Nanowire Film Realized by Printed Precursor Inks.

This paper demonstrates an easily prepared novel material and approach to producing aligned nickel (Ni) nanowires having unique and customizable structures on a variety of substrates for electronic and magnetic applications. This is a new approach to producing printed metallic Ni structures from precursor materials, and it provides a novel technique for nanowire formation during reduction. This homogeneous solution can be printed in ambient conditions, and it forms aligned elemental Ni nanowires over large areas upon heating in the presence of a magnetic field. The use of templates or subsequent purification are not required. This technique is very flexible, and allows the preparation of unique patterns of nanowires which provides opportunities to produce structures with enhanced anisotropic electrical and magnetic properties. An example of this is the unique fabrication of aligned nanowire grids by overlaying layers of nanowires oriented at different angles with respect to each other. The resistivity of printed and cured films was found to be as low as 560 µΩ∙cm. The saturation magnetization was measured to be 30 emu∙g-1, which is comparable to bulk Ni. Magnetic anisotropy was induced with an axis along the direction of the applied magnetic field, giving soft magnetic properties.

Discovery of dual Axl/VEGF-R2 inhibitors as potential anti-angiogenic and anti-metastatic drugs for cancer chemotherapy.

Axl tyrosine kinase has been shown to be involved in multiple pathways contributing to tumor development, angiogenesis, and metastasis. High Axl expression has been observed in many human tumors where it appears to confer aggressive tumor behavior. Here we present several series of dual Axl-VEGF-R2 kinase inhibitors based on extensive optimization of an acyl diaminotriazole. It was hypothesized that dual inhibition of these two receptor tyrosine kinases may have a synergistic affect in inhibiting tumor angiogenesis and metastasis. One of these molecules, R916562 showed comparable activity to Sunitinib in two mouse tumor xenograft models and a mouse corneal micropocket model.

Enantioselective synthesis of an octahydroindolizine (indolizidine) alcohol using an enzymatic resolution.

A homo-chiral synthesis of (7R,8aS)-octahydro-5,5-dimethylindolizin-7-amine 8 and (7S, 8aS)-octahydro-5,5-dimethylindolizin-7-ol 9, amine building blocks which have found applications within the pharmaceutical industry, is presented. The approach uses a Novozym 435-mediated kinetic resolution of racemic octahydroindolizine (indolizidine) alcohol 13 as a key step (up to 100 g scale).

Enantioselective synthesis of cis-3-fluoropiperidin-4-ol, a building block for medicinal chemistry.

The first enantioselective route to both enantiomers of cis-1-Boc-3-fluoropiperidin-4-ol, a highly prized building block for medicinal chemistry, is reported. An enantioselective fluorination is employed, taking advantage of the methodology reported by MacMillan, which uses a modified cinchona alkaloid catalyst. In studying the fluorination reaction, we have shown that the catalyst can be replaced by commercially available primary amines, including α-methylbenzylamine, with similar levels of enantioselectivity. The piperidinols are readily crystallized to obtain enantiopure material.

Gastric cancer surgery--a balance of risk and radicality.

INTRODUCTION: The aim of this study was to determine whether tailoring the extent of resection would allow radical gastric cancer surgery to be performed safely in a UK population. PATIENTS AND METHODS: A total of 180 consecutive patients (median age 70 years; male:female ratio 2:1) undergoing resection for gastric adenocarcinoma with curative intent were studied. Extent of lymphadenectomy was based upon pre-operative and intra-operative staging, and balanced against the patient's age and fitness. RESULTS: In the study group, 83 patients underwent subtotal or distal partial gastrectomy and 97 patients underwent total or proximal partial gastrectomy. Operative procedures were: D1 lymphadenectomy (n = 62); modified (spleen and pancreas pre-serving) D2 lymphadenectomy (n = 73); D2 lymphadenectomy (n = 42); and extended resection (n = 3). TNM classification was: stage 1 (n = 45); stage 2 (n = 37); stage 3 (n = 61); and stage 4 (n = 37). Of the patients, 48 developed postoperative complications including 17 patients with a major surgical complication. The in-hospital mortality was 1.7% (3 of 180). Predicted mortality according to POSSUM and P-POSSUM was 21.4% and 7.8%, respectively. Disease-specific 5-year survival according to stage was 85.4%, 64.2%, 33.3%, and 6.9%. CONCLUSIONS: By tailoring the extent of resection and balancing risk and radicality, gastric cancer surgery can be performed with low mortality in Western patients.

Graseby MS16A and MS26 syringe drivers: reported effectiveness of an online learning programme.

Syringe drivers are commonly used within palliative care to assist with maintaining adequate symptom control. Two of the most common, the Graseby MS16A and MS26, have been associated with a number of serious clinical incidents which have been linked, in part, to inadequate training. This article reports on the results of an online learning programme on managing syringe drivers in palliative care undertaken by 5380 learners between September 2003 and October 2006. The results show that this flexible form of learning environment is acceptable to learners and can lead to improvements in both knowledge and understanding of palliative care issues. Using an online learning model allows large numbers of learners to be educated at minimal cost to either them or their organisation.

High-throughput purification of combinatorial libraries II: Automated separation of single diastereomers from a 4-amido-pyrrolidone library containing intentional diastereomer pairs.

A 4-amido-pyrrolidone library that was intentionally synthesized as pairs of diastereomers was produced by solution-phase parallel syntheses and purified by an automated high-throughput purification system. A total of 2592 4-amido-pyrrolidinones were ultimately isolated as single diastereomers from a matrix of 1920 syntheses. After the four-step synthesis and HPLC purification, the average yield of a single diastereomer was 36.6%. The average chemical purity was >90%, and the average diastereomeric purity was >87%. The choice of chiral amines used to make amides with heterocyclic acid chlorides had a dramatic effect on success. Analysis of the relationship between amines used for synthesis and the diastereomeric separation showed that amides made from chiral 1,2-amino alcohols gave superior separation to amides from chiral morpholines. The presence of a hydrogen bond donor on the amide side chain seems to be required for a better diastereomeric separation.

High-throughput purification of combinatorial libraries I: a high-throughput purification system using an accelerated retention window approach.

We have developed a high-throughput purification system to purify combinatorial libraries at a 50-100-mg scale with a throughput of 250 samples/instrument/day. We applied an accelerated retention window method to shorten the purification time and targeted one fraction per injection to simplify data tracking, lower QC workload, and simplify the postpurification processing. First, we determined the accurate retention time and peak height for all compounds using an eight-channel parallel LC/UV/MS system, and calculated the specific preparative HPLC conditions for individual compounds. The preparative HPLC conditions include the compound-specific gradient segment for individual compounds with a fixed gradient slope and the compound-specific UV or ELSD threshold for triggering a fraction collection device. A unique solvent composition or solvent strength was programmed for each compound in the preparative HPLC in order to elute all compounds at the same target time. Considering the possible deviation of the predicted retention time, a 1-min window around the target time was set to collect peaks above a threshold based on UV or ELSD detection. Dual column preparative instruments were used to maximize throughput. We have purified more than 500 000 druglike compounds using this system in the past 3 years. We report various components of this high-throughput purification system and some of our purification results.

Quality control in combinatorial chemistry: determination of the quantity, purity, and quantitative purity of compounds in combinatorial libraries.

The quality of combinatorial libraries determines the success of biological screening in drug discovery programs. In this paper, we evaluate and compare various methods for measuring identity, purity, and quantity (yield) of combinatorial libraries. Determination of quantitative purity reveals the true library quality and often indicates potential quality problems before full-scale library production. The relative purity can be determined for every member in a large library in a high-throughput mode, but must be cautiously interpreted. In particular, many impurities are not observable by relative purity measurements using detectors such as UV(214), UV(254), and evaporative light-scattering detection. These "invisible" impurities may constitute a significant portion of the sample weight. We found that TFA, plastic extracts, inorganic compounds, and resin washout are among these impurities. With compelling evidence, we reach a conclusion that purification is the only way to remove "invisible" impurities and improve the quantitative purity of any compound even though some compounds may have a high relative purity before purification.

Speeding up the diagnosis of oesophago-gastric cancer.

National referral guidelines have been developed for patients with suspected oesphago-gastric cancer with the aim of reducing the delay from presentation to referral and, therefore, reducing overall delay in diagnosis. This study evaluates the impact of these guidelines and shows that they have resulted in a significant decrease in the time from referral to endoscopy for patients. Nurses can further contribute to this by increasing patient awareness of symptoms. A course is being developed to provide the necessary knowledge.