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NURBS stands for Non-Uniform Rational B-Splines, the popular mathematical tool used for computer-aided geometric design (CAGD) of free-form curves and surfaces. The geometrical shape of NURBS curves and surfaces is mainly controlled by their control points and the corresponding weights. This chapter concerns the identification of NURBS curves and surfaces from discrete points measured on coordinate measuring machines (CMMs), laser scanners or other digitizing equipments. The complete process is divided into two steps. The weights of the control points are first identified with singular value decomposition (SVD) or symmetric eigen value decomposition (SEVD) techniques through a linear homogeneous system. The control points are then solved with linear least squares fitting techniques. Both interpolation (exact) and fitting (approximate) solutions are studied. The emphasis of the present chapter is on SVD and SEVD applications during the first step for the identification of the weights.
Selective laser melting (SLM) is characterized by highly localized heat input and short interaction times, which lead to large thermal gradients. In this research, nine different materials are processed via SLM and compared. The resulting microstructures are characterized by optical and scanning electron microscopy. Residual stresses are measured qualitatively using a novel deflection method and quantitatively using X-ray diffraction. Microcracking, surface oxidation and the anisotropy of the residual stress are discussed. The different phenomena interacting with the buildup of residual stress make it difficult to distinguish the possible correlations between material parameters and the magnitude of residual stresses.
Compared with vaccines, antivirals for curbing COVID-19 (SARS-CoV-2 infection) have been developed at a much lower pace. Favipiravir has proven efficacious (in hamsters) but only at a very high dose which may not be feasible in humans. Remdesivir is the sole antiviral approved by the US FDA, but it has not been extensively evaluated for its safety. EIDD-1931 and EIDD-2801 have not been evaluated clinically. Mpro (protease) inhibitors likewise need to be subjected to clinical efficacy and safety studies. Remdesivir is a C-nucleoside and this class of compounds should be further evaluated. Polyanionic substances interfering with virus adsorption to the host cells have not been explored. They may possibly be administered by inhalation. Corticosteroids (such as dexamethasone), while virus-stimulating rather than inhibitory, may counteract the ‘cytokine storm’. Combination of (two or more of) the compounds mentioned above may offer an increased benefit through a synergistic interaction.
Several guanosine analogues, i.e. acyclovir (and its oral prodrug valaciclovir), penciclovir (in its oral prodrug form, famciclovir) and ganciclovir, are widely used for the treatment of herpesvirus [i.e. herpes simplex virus type 1 (HSV-1), and type 2 (HSV-2), varicella-zoster virus (VZV) and/or human cytomegalovirus (HCMV)] infections. In recent years, several new guanosine analogues have been developed, including the 3-membered cyclopropylmethyl and -methenyl derivatives (A-5021 and synguanol) and the 6-membered D- and L-cyclohexenyl derivatives. The activity of the acyclic/carbocyclic guanosine analogues has been determined against a wide spectrum of viruses, including the HSV-1, HSV-2, VZV, HCMV, and also human herpesviruses type 6 (HHV-6), type 7 (HHV-7) and type 8 (HHV-8), and hepatitis B virus (HBV). The new guanosine analogues (i.e. A-5021 and D- and L-cyclohexenyl G) were found to be particularly active against those viruses (HSV-1, HSV-2, VZV) that encode for a specific thymidine kinase (TK), suggesting that their antiviral activity (at least partially) depends on phosphorylation by the virus-induced TK. Marked antiviral activity was also noted with A-5021 against HHV-6 and with D- and L-cyclohexenyl G against HCMV and HBV. The antiviral activity of the acyclic/carbocyclic nucleoside analogues could be markedly potentiated by mycophenolic acid, a potent inhibitor of inosine 5'-monophosphate (IMP) dehydrogenase. The new carbocyclic guanosine analogues (i.e. A-5021 and D- and L-cyclohexenyl G) hold great promise, not only as antiviral agents for the treatment of herpesvirus infections, but also an antitumor agents for the combined gene therapy/chemotherapy of cancer, provided that (part of) the tumor cells have been transduced by the viral (HSV-1, VZV) TK gene.
No abstract is provided for this article.
Various 5-substituted 2'-deoxyuridine (dUrd), 2'-deoxycytidine (dCyd), 1-beta-D-arabinofuranosyluracil (araU) and 1-beta-D-arabinofuranosylcytosine (araC) analogues have been investigated for their stimulatory effect on the growth of a thymidylate (dTMP) synthetase-deficient murine mammary carcinoma cell line (FM3A/TS-) that is auxotrophic for thymidine (dThd). Such stimulatory effect may be considered as indicative for the incorporation of the nucleoside analogue into host cell DNA. Based on this premise, several dUrd analogues were found to be incorporated into FM3A/TS- cell DNA (in decreasing order of incorporation): 5-bromo-dUrd greater than 5-chloro-dUrd greater than 5-(3-hydroxy-1-propynyl)-dUrd greater greater than 5-(1-pentynyl)-dUrd approximately 5-(1-propynyl)-dUrd approximately 5-iodo-dUrd greater than 5-(5-carboxy-1-hexenyl)-dUrd greater than 5-(3,3-dimethyl-1-butynyl)-dUrd greater than 5-ethyl-dUrd greater than 5-(5-chloro-1-pentynyl)-dUrd greater than 5-ethynyl-dUrd approximately 5 vinyl-dUrd greater than 5-phenylethynyl-dUrd greater than 5-(5-cyano-1-pentenyl)-dUrd greater than 5-(1-propenyl)-dUrd greater than 5-(1-hexynyl)-dUrd greater than 5-(5-hexyn-1-enyl)-dUrd. Among the 5-substituted dCyd analogues, 5-methyl-dCyd, 5-chloro-dCyd, 5-bromo-dCyd and 5-iodo-dCyd were also found to stimulate cell growth, and are therefore assumed to be incorporated into FM3A/TS- cell DNA. Since the stimulatory effects of these compounds on FM3A/TS- cell proliferation were suppressed in the presence of a Cyd deaminase inhibitor (tetrahydrouridine) or dCMP deaminase inhibitor (2'-deoxytetrahydrouridine), it is surmised that the dCyd analogues are first deaminated to the corresponding dUrd analogues before they are incorporated into DNA. None of the 5-substituted araU or araC analogues tested were able to sustain the growth of FM3A/TS- cells. It is postulated, therefore, that these araU or araC analogues are not incorporated to any appreciable extent into the DNA of FM3A/TS- cells, or, if they are incorporated, prevent cell growth. Thus, the dTMP synthetase-deficient FM3A/TS- cell line represents a unique system to distinguish those pyrimidine nucleoside analogues that are able to sustain cell growth and, therefore, assumed to be incorporated into the host cell DNA from those pyrimidine nucleoside analogues that are not.
