Publications

Feature-based Computer Automated Process Planning applications often suffer from exponential growth of the search space and thus CPU time, with increasing complexity of a part. This paper will explain some methods that were used to improve the response time of a newly developed CAPP system that is capable of generating net-shaped process plans, called non-linear process plans, containing several alternatives. One method to improve the performance is called Opportunistic process planning. The approach consists of dividing the features into two sets: one set, called the important features, is used to generate a process plan; the other features, called non-important features, are added to the process plan afterwards. This generation method highly resembles the reasoning pattern of a human process planner. Another innovative method for performance improvement is called Feature grouping. This method combines features that have strong resemblance, and considers them as only one feature during the process plan generation. Other reasoning methods, described in this paper, are: combined variant/generative planning and constraint-based search. All of the above-mentioned methods allow us to reduce the search space significantly. The developments have been carried out in the framework of the Esprit project 6805, COMPLAN (Concurrent Manufacturing Planning and Shop Control for small batch production). The COMPLAN CAPP system is able to cover a wide workpiece spectrum (customizable towards specific needs). It has been intensively tested for three workpiece families (i.e. hydraulic valves, bending tool-knives and prismatic parts) of a pilot end-user, a producer of sheet metal machinery. The system can be easily extended towards other part spectra. Also the embedded process-planning knowledge is easy to configure or alter.

While 25 compounds have been formally licensed for the treatment of HIV infection (AIDS), only seven licensed products are currently available for the treatment of chronic hepatitis B virus (HBV) infection: interferon-α, pegylated interferon-α, lamivudine, adefovir (dipivoxil), entecavir, telbivudine and tenofovir (disoproxil fumarate). In contrast to the treatment of HIV infections where the individual drugs are routinely used in combination, for the treatment of chronic HBV infection the individual drugs are generally used in monotherapy. In principle, combination drug therapy should allow reducing the likelihood of drug-resistant development.

Cyclosporin A (CsA) inhibits the in vitro replication of HCV subgenomic replicons. We here report on the potent anti-HCV activity of the non-immunosuppressive cyclosporin DEBIO-025. The 50% effective concentration for inhibition of HCV subgenomic replicon replication in Huh 5-2 cells (luciferase assay) by DEBIO-025 was 0.27 +/- 0.03 microg/mL and for CsA 2.8 +/- 0.4 microg/mL. The concentration that reduced the growth of exponentially proliferating Huh 5-2 cells by 50% was greater than 27 microg/mL for DEBIO-025 and 12 +/- 6 microg/mL for CsA, resulting in a selectivity index of approximately 900 for DEBIO-025 and 40 for CsA. The superior activity of DEBIO-025, as compared with CsA, was corroborated by monitoring HCV RNA levels in Huh 5-2, two other HCV subgenomic replicon-containing cell lines, and by monitoring the luciferase signal and viral antigen production in hepatoma cells that had been infected with an infectious full-length chimeric HCV construct. The combination of interferon alpha 2a with either CsA or DEBIO-025 resulted in an additive to slightly synergistic antiviral activity. DEBIO-025, at concentrations of 0.5 and 1 microg/mL, was able to clear cells from their HCV replicon within three to four passages, whereas treatment with CsA at the same concentrations for seven consecutive passages did not result in clearance of the HCV replicon. In conclusion, DEBIO-025, a compound that is also endowed with potent anti-HIV activity and is well tolerated in animals and humans, may form an attractive new option for the therapy of HCV infections, particularly in HCV/HIV co-infected patients.

The optically pumped Cs beam frequency standard under development in our laboratory was first evaluated in 1993. The short term stability was /spl sigma//sub y/(/spl tau/) is 5.5/spl middot/10/sup -13//spl tau//sup - 1/2 /. The accuracy has been estimated to 1.1/spl middot/10/sup -13/, mainly limited by the distributed phase shift. After modification of the cavity, a new evaluation is in progress and is presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>

Different arabinosides and ribosides, viz. Ara-DDA or 9(1-beta-D-arabinofuranosyl) 1,3-dideazaadenine (6), Ara-NDDP or 9(1-beta-D-arabinofuranosyl) 4-nitro-1,3-dideazapurine (7), Ara-DKP or 1(1-beta-D-arabinofuranosyl) diketopiperazine (8), Ribo-DDA or 9(1-beta-D-ribofuranosyl) 1,3-dideazaadenine (9) and Ribo-NDDP or 9(1-beta-D-ribofuranosyl) 4-nitro-1,3-dideazapurine (10) have been synthesized as probable antiviral agents. The arabinosides have been synthesized using the catalyst TDA-1 that causes stereospecific formation of beta-nucleosides while a one-pot synthesis procedure was adopted for the synthesis of the ribonucleosides where beta-anomers were obtained in higher yields. All the five nucleoside analogs have been screened for antiviral property against HIV-1 (IIIB), HSV-1 and 2, parainfluenza-3, reovirus-1 and many others. It was observed that arabinosides had greater inhibitory action than ribosides. The compound 7 or Ara-NDDP has shown maximum inhibition of HIV-1 replication than the rest of the molecules with an IC50 of 79.4 microg/mL.