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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. Opportunistic process planning can remedy this drawback. The approach consists of dividing the features into two sets : one set, called the important features, are used to generate a process plan; the other features, called non-important features, are added to the process plan afterwards. This generation method resembles much the reasoning pattern of a human process planner. The developments are carried out in the framework of the ongoing Esprit project 6805 COMPLAN. Other reasoning methods, used in the project and described in this paper, are : combined variant/generative planning, non linear process plans, Petri nets, and feature based reasoning.
Non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs) have become an inherent ingredient of the drug combination schemes that are currently used in the treatment of human immunodeficiency virus type 1 (HIV-1) infections. Starting from the 1-[(2-hydroxyethoxy)methyl]-6-(phenylsulfanyl)thymine (HEPT) and 4,5,6,7-tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one and -thione (TIBO) derivatives, numerous classes of compounds have been described as NNRTIs. Only three compounds have so far been approved for clinical use: nevirapine, delavirdine, and efavirenz. NNRTIs are notorious for rapidly leading to virus-drug resistance development, primarily based on the emergence of the K103N and Y181C mutations in the HIV-1 RT. Newer NNRTIs, such as capravirine, dapivirine (TMC 125), and DPC 083, are resilient to these 'NNRTI' mutations, and, therefore, offer considerable promise as future anti-HIV-1 drugs. NNRTIs are targeted at a specific 'pocket' binding site within the HIV-1 RT, that is distinct from, but both spatially and functionally related to, the catalytic site, where the nucleoside RT inhibitors (NRTIs) and nucleotide RT inhibitors (NtRTIs) interact. NNRTIs have acquired a definitive position, as part of a combination regimen with NRTIs and NtRTIs, in the first-line treatment of HIV-1 infections.
In product design, a CAD model often needs to be constructed from a physical part. This process is called reverse engineering and is performed through dimensional digitising and CAD modelling. The dimensional digitising results in a cloud of points, which are input for the CAD modelling of surfaces corresponding to the object's features. Consistent with these features, some of the modelled surfaces need to join with positional, tangential or curvature continuity. This paper reports on the incorporation of these geometric boundary conditions in the CAD modelling of free-form surfaces from a cloud of points with non-uniform rational B-splines (NURBS). The described methods are illustrated with some practical, industrial examples and some alternative solutions are briefly described.
No abstract is provided for this article.
During selective laser melting, the irradiated material experiences large temperature fluctuations in a short time which causes unwanted thermal stresses. In order to assess thermal stresses in a simple and fast way, a new pragmatic method is developed, namely the bridge curvature method. The bridge curvature method is used to assess and qualitatively compare the influence of different laser scan patterns, laser parameter settings and more fundamental process changes on residual stresses. The results from the experiments, as well as the findings from literature, lead to two general conclusions: changes that reduce the high temperature gradient, like using short scan vectors and preheating of the base plate, reduce the thermal stresses. And, thermal stresses in a particular direction can be reduced by optimal choice of the orientation of scan vectors. The experiments indicate the reliability of the bridge curvature method. Statistical analysis is used to check the repeatability of the method and to quantify the uncertainties during measurement.
No abstract is provided for this article.
Selective laser sintering (SLS) is one of the most rapidly growing rapid prototyping techniques (RPT). This is mainly due to its suitability to process almost any material: polymers, metals, ceramics (including foundry sand) and many types of composites. The material should be supplied as powder that may occasionally contain a sacrificial polymer binder that has to be removed (debinded) afterwards. The interaction between the laser beam and the powder material used in SLS is one of the dominant phenomena that defines the feasibility and quality of any SLS process. This paper surveys the current state of SLS in terms of materials and lasers. It describes investigations carried out experimentally and by numerical simulation in order to get insight into laser‐material interaction and to control this interaction properly.
The name of Antonín Holý has become synonymous for the era of acyclic nucleoside phosphonates (ANPs), which started with (S)-HPMPA as the prototype and (S)-HPMPC (cidofovir) as the first marketed compound. It has now evolved to a number of compounds clinically used in the treatment of HIV and hepatitis B virus infections, either as such [tenofovir disoproxil fumarate (TDF, Viread®)] or in combination [Truvada®, Atripla®, Complera®, Stribild®]. Truvada has also been approved for the prevention of HIV infections. Forthcoming is a new formulation of tenofovir (TAF: tenofovir alafenamide). Also forthcoming are several "quad" drug combinations containing either TDF or TAF. Other ANPs, based on either an alkoxy side chain or 5-azacytosine heterocycle seem highly promising and worth further pursuing.
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No abstract is provided for this article.
A marked virus-inhibiting potency is obtained in the serum after intraperitoneal injection of polyacrylic acid (PAA) and polymethacrylic acid (PMAA) in mice. Much higher antiviral levels were reached than for other related polymers including dextran sulfate, heparin, polyvinyl sulfate, pyran copolymer, polystyrene sulfonate, and macrodex. The broad antiviral action of PAA and PMAA was attributed both to a direct interference with the virus-cell interaction and the viral ribonucleic acid metabolism and to the formation of an interferon-like factor. Both polyanions differed in interferon-inducing ability: highest serum interferon titer was obtained 18 hr after the intraperitoneal injection of PAA. The mechanism of interferon production by PAA and PMAA is discussed. As described previously for Sindbis virus and endotoxin, the animals also became hyporeactive after injection of PAA.