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.
Double-stranded RNA, made as an intermediary substance in the replication of most, if not all, viruses, may play a much more important role in the pathogenesis and the recovery from virus infections than has hitherto been suspected. Apparently, dsRNA is used by both the challenge virus and the host cell in an attempt to gain "molecular control." Double-stranded RNA exerts a set of effects, which may be well balanced, not only at the level of the individual cell but also at the complex assemblage of these cells termed the organism (Fig. 1). In the cell, interferon synthesis is triggered, although interferon mRNA translation may not occur if dsRNA shuts off protein synthesis too quickly. In the whole organism, the disease severity will depend on how certain toxic reactions evoked by infection (such as cell necrosis and fever) are counterbalanced by an increase in the host defense mechanisms (for example, immune responsiveness and interferon production). Many aspects of the response, relating to either progress of, or recovery from, the disease, can be explained on the basis of a dsRNA. In addition to drawing attention to the biodynamic role of dsRNA, our hypothesis suggests specific experimental vectors designed to enhance our information on the molecular basis of the morbid process which occurs with viral infection. Finally, we suggest that, although the dsRNA molecule may be viewed as a rather simple unit structure, the opportunity for further diversity in the biological activity of a given dsRNA molecule always exists. Namely, each deviation from a perfectly double-helical arrangement introduces the possibility for emphasizing one biological reactivity at the expense of another. This latter structure-activity property may partially account for the extreme apparent diversity, commonly encountered, in the presentations of virologic illness. Appendix note added in proof. Subsequent to submission of this text, we have found that the potent mitogen effect of dsRNA for lymphocytes (murine and human) is also exquisitively sensitive to the fidelity in base pairing of the input polymer pair (59). For example, infrequent "loops" (one nucleotide per 20 base pairs) in an otherwise perfectly helical rI(n) (.) rC(n) molecule [for example, rI(n) (.) r(C(19,)U)(n)] strongly changes its mitogenic properties. This observation, which supports our thesis that a "fine structure" term can be developed for other reactions triggered by dsRNA's in biological systems, emphasizes that diverse biological effects may be encountered with an ostensibly uniform family of dsRNA's.
Scaffold hopping is a frequently-used strategy in the development of non-nucleoside reverse transcriptase inhibitors. Herein, CH(CN)-DAPYs were designed by hopping the cyano-methylene linker of our previous published CH(CN)-DABOs onto the etravirine (ETR). Eighteen CH(CN)-DAPYs were synthesized and evaluated for their anti-HIV activity. Most compounds exhibited promising activity against wild-type (WT) HIV-1. Compounds <b>B4</b> (EC<sub>50</sub> = 6 nM) and <b>B6</b> (EC<sub>50</sub> = 8 nM) showed single-digit nanomolar potency against WT HIV-1. Moreover, these two compounds had EC<sub>50</sub> values of 0.06 and 0.08 μM toward the K103N mutant, respectively, which were comparable to the reference efavirenz (EFV) (EC<sub>50</sub> = 0.08 μM). The preliminary structure-activity relationship (SAR) indicated that introducing substitutions on C2 of the 4-cyanophenyl group could improve antiviral activity. Molecular docking predicted that the cyano-methylene linker was positioned into the hydrophobic cavity formed by Y181/Y188 and V179 residues.
EDM causes thermally induced residual tensile stress to form in the top layer of a machined surface.This paper deals with a mechanical method for measuring the residual stress profile in function of depth beneath the surface.Deformation due to stress relaxation is measured while removing influenced material containing residual stress.The measurement is done for samples of tool steel, machined with Wire EDM.Results show that the maximum tensile stress and the penetration depth of tensile stress decrease with increasing number of finishing steps.In some cases, after rough W -EDM, a relaxation of residual stress in time is observed.The harmful influence of residual stresses is clear after rough W-EDM of thin beams: the rough machining causes major deformation of the part, which makes further finishing impossible.
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