Androgen deprivation results in time-dependent hypoxia in LNCaP prostate tumours; informed scheduling of the bioreductive drug AQ4N improves treatment response

Androgen withdrawal induces hypoxia in androgen-sensitive tissue; this is important as in the tumour microenvironment hypoxia is known to drive malignant progression. This study examined the time-dependent effect of androgen deprivation therapy (ADT) on tumour oxygenation and investigated the role of ADT-induced hypoxia on malignant progression in prostate tumours. LNCaP xenografted tumours were treated with anti-androgens and tumour oxygenation measured. Dorsal skin fold chambers (DSF) were used to image tumour vasculature in vivo. Quantitative PCR (QPCR) identified differential gene expression following treatment with bicalutamide. Bicalutamide and vehicle-only treated tumours were re-established in vitro and invasion and sensitivity to docetaxel were measured. Tumour growth delay was calculated following treatment with bicalutamide combined with the bioreductive drug AQ4N. Tumour oxygenation measurements showed a precipitate decrease following initiation of ADT. A clinically relevant dose of bicalutamide (2mg/kg/day) decreased tumour oxygenation by 45% within 24h, reaching a nadir of 0.09% oxygen (0.67±0.06 mmHg) by day 7; this persisted until day 14 when it increased up to day 28. Using DSF chambers, LNCaP tumours treated with bicalutamide showed loss of small vessels at days 7 and 14 with revascularization occurring by day 21. QPCR showed changes in gene expression consistent with the vascular changes and malignant progression. Cells from bicalutamide-treated tumours were more malignant than vehicle-treated controls. Combining bicalutamide with AQ4N (50mg/kg; single dose) caused greater tumour growth delay than bicalutamide alone. This study shows that bicalutamide-induced hypoxia selects for cells that show malignant progression; targeting hypoxic cells may provide greater clinical benefit.

Retrieving designs from a sketch using an automated GT coding and classification system

While the retrieval of existing designs to prevent unnecessary duplication of parts is a recognised strategy in the control of design costs the available techniques to achieve this, even in product data management systems, are limited in performance or require large resources. A novel system has been developed based on a new version of an existing coding system (CAMAC) that allows automatic coding of engineering drawings and their subsequent retrieval using a drawing of the desired component as the input. The ability to find designs using a detail drawing rather than textual descriptions is a significant achievement in itself. Previous testing of the system has demonstrated this capability but if a means could be found to find parts from a simple sketch then its practical application would be much more effective. This paper describes the development and testing of such a search capability using a database of over 3000 engineering components.

Stimulating design reuse through automated coding

In designing new product the ability to retrieve drawings of existing components is important if costs are to be controlled by preventing unnecessary duplication if parts. Component coding and classification systems have been used successfully for these purposes but suffer from high operational costs and poor usability arising directly from the manual nature of the coding process itself. A new version of an existing coding system (CAMAC) has been developed to reduce costs by automatically coding engineering drawings. Usability is improved be supporting searches based on a drawing or sketch of the desired component. Test results from a database of several thousand drawings are presented.

Data Protection and Packet Mode in the Distributed Information Measurement and Control System for Research in Physics

The present paper is devoted to creation of cryptographic data security and realization of the packet mode in the distributed information measurement and control system that implements methods of optical spectroscopy for plasma physics research and atomic collisions. This system gives a remote access to information and instrument resources within the Intranet/Internet networks. The system provides remote access to information and hardware resources for the natural sciences within the Intranet/Internet networks. The access to physical equipment is realized through the standard interface servers (PXI, CАМАC, and GPIB), the server providing access to Ethernet devices, and the communication server, which integrates the equipment servers into a uniform information system. The system is used to make research task in optical spectroscopy, as well as to support the process of education at the Department of Physics and Engineering of Petrozavodsk State University.