Magnetic Field Mapping with a Squid Device

An ability to experimentally determine the magnetic field in the region close to the face of an eddy current coil, the normal location of the work piece, is very desirable. It allows confirmation of the theoretical design of complex coils, offers a potential method for rapid characterization of commercial coils, and may well provide a uniquely direct method of looking at coil/flaw interactions. However, the small size of typical eddy current probes presents some extreme problems in this regard. For the past year we have been attempting to determine the best method to use for measuring the field configuration in the near-field regio

The zinc finger domain of Wilms' tumor 1 suppressor gene (WT1) behaves as a dominant negative, leading to abrogation of WT1 oncogenic potential in breast cancer cells

Abstract Introduction There is growing evidence that the Wilms' tumor 1 suppressor gene (WT1) behaves as an oncogene in some forms of breast cancer. Previous studies have demonstrated that the N-terminal domain of WT1 can act as a dominant negative through self-association. In the studies presented here we have explored the potential for the zinc finger domain (ZF) of WT1 to also have dominant-negative effects, and thus further our understanding of this protein. Methods Using full-length and ZF-only forms of WT1 we assessed their effect on the WT1 and c-myc promoter using luciferase and chromatin immunoprecipitation assays. The gene expression levels were determined by quantitative real-time RT-PCR, northern blot and western blot. We also assessed the effect of the ZF-only form on the growth of breast cancer cell lines in culture. Results Transfection with WT1–ZF plasmids resulted in a stronger inhibition of WT1 promoter than full-length WT1 in breast cancer cells. The WT1–ZF form lacking the lysine–threonine–serine (KTS) insert (ZF - KTS) can bind to the majority of WT1 consensus sites throughout the WT1 promoter region, while the ZF containing the insert (ZF + KTS) form only binds to sites in the proximal promoter. The abundances of endogenous WT1 mRNA and protein were markedly decreased following the stable expression of ZF - KTS in breast cancer cells. The expressions of WT1 target genes, including c-myc, Bcl-2, amphiregulin and TERT, were similarly suppressed by ZF - KTS. Moreover, WT1–ZF - KTS abrogated the transcriptional activation of c-myc mediated by all four predominant isoforms of WT1 (including or lacking alternatively spliced exons 5 and 9). Finally, WT1–ZF - KTS inhibited colony formation and cell division, but induced apoptosis in MCF-7 cells. Conclusion Our observations strongly argue that the WT1–ZF plasmid behaves as a dominant-negative regulator of the endogenous WT1 in breast cancer cells. The inhibition on proliferation of breast cancer cells by WT1–ZF - KTS provides a potential candidate of gene therapy for breast cancer

Phase I studies of AZD1208, a proviral integration Moloney virus kinase inhibitor in solid and haematological cancers.

BACKGROUND:Proviral integration Moloney virus (PIM) kinases (PIM1, 2 and 3) are overexpressed in several tumour types and contribute to oncogenesis. AZD1208 is a potent ATP-competitive PIM kinase inhibitor investigated in patients with recurrent or refractory acute myeloid leukaemia (AML) or advanced solid tumours. METHODS:Two dose-escalation studies were performed to evaluate the safety and tolerability, and to define the maximum tolerated dose (MTD), of AZD1208 in AML and solid tumours. Secondary objectives were to evaluate the pharmacokinetics, pharmacodynamics (PD) and preliminary efficacy of AZD1208. RESULTS:Sixty-seven patients received treatment: 32 in the AML study over a 120-900 mg dose range, and 25 in the solid tumour study over a 120-800 mg dose range. Nearly all patients (98.5%) in both studies experienced adverse events, mostly gastrointestinal (92.5%). Dose-limiting toxicities included rash, fatigue and vomiting. AZD1208 was not tolerated at 900 mg, and the protocol-defined MTD was not confirmed. AZD1208 increased CYP3A4 activity after multiple dosing, resulting in increased drug clearance. There were no clinical responses; PD analysis showed biological activity of AZD1208. CONCLUSIONS:Despite the lack of single-agent clinical efficacy with AZD1208, PIM kinase inhibition may hold potential as an anticancer treatment, perhaps in combination with other agents

The case for developing publicly-accessible datasets for health services research in the Middle East and North Africa (MENA) region

<p>Abstract</p> <p>Background</p> <p>The existence of publicly-accessible datasets comprised a significant opportunity for health services research to evolve into a science that supports health policy making and evaluation, proper inter- and intra-organizational decisions and optimal clinical interventions. This paper investigated the role of publicly-accessible datasets in the enhancement of health care systems in the developed world and highlighted the importance of their wide existence and use in the Middle East and North Africa (MENA) region.</p> <p>Discussion</p> <p>A search was conducted to explore the availability of publicly-accessible datasets in the MENA region. Although datasets were found in most countries in the region, those were limited in terms of their relevance, quality and public-accessibility. With rare exceptions, publicly-accessible datasets - as present in the developed world - were absent. Based on this, we proposed a gradual approach and a set of recommendations to promote the development and use of publicly-accessible datasets in the region. These recommendations target potential actions by governments, researchers, policy makers and international organizations.</p> <p>Summary</p> <p>We argue that the limited number of publicly-accessible datasets in the MENA region represents a lost opportunity for the evidence-based advancement of health systems in the region. The availability and use of publicly-accessible datasets would encourage policy makers in this region to base their decisions on solid representative data and not on estimates or small-scale studies; researchers would be able to exercise their expertise in a meaningful manner to both, policy makers and the public. The population of the MENA countries would exercise the right to benefit from locally- or regionally-based studies, versus imported and in 'best cases' customized ones. Furthermore, on a macro scale, the availability of regionally comparable publicly-accessible datasets would allow for the exploration of regional variations and benchmarking studies.</p