Surface topography measurements are vital in industrial quality control. Linear roughness measurements are among the most preferred methods, being quick to perform and easy to interpret. The ISO 16610 standard series prescribes filters that can be used for most cases, but has limitations for restricted measurement lengths. This is because the standard filter type is a Gaussian filter, which like most instances of kernel convolution filters has no output near the edges of the profile, effectively shortening the length of the filtered output profile as compared to the input. In some cases, this leads to a lack of representative data after filtration. Especially in fields such as Additive Manufacturing (AM) this becomes a problem, due to the high "roughness to measurable data length"-ratio that characterizes complex AM parts. This paper describes a method that allows to overcome this limitation: A method for circular padding of short measured tracks is described and validated. A flexible profile data post-processing tool was developed in MATLAB to grant users more control over the data analysis. Results obtained from roughness profiles long enough for normal ISO procedures are shown to not change significantly when circularly padded. When only a shorter section of the data is available, where the standard protocol would not be able to compute a filtered profile and related parameters anymore, the circular padding method is shown to lead to results that are in good agreement with the ISO standard procedures.
A powder metallurgy (PM) process to fabricate alumina parts through indirect selective laser sintering (SLS) of spherical alumina-polyamide composite powder is presented. The PM process includes powder production, SLS, debinding and furnace sintering. Three different strategies are investigated in order to improve the density of the final alumina parts: laser remelting, warm isostatic pressing (WIP), and different infiltration techniques which use alumina containing suspensions: pressureless infiltration and infiltration under pressure (i.e. squeeze infiltration). Furthermore, microstructural and geometrical changes which occur during the PM process are investigated.
Human papillomavirus (HPV) induced epithelial cell proliferation is responsible for a broad range of lesions. Treatment of such lesions is characterized by a high relapse rate. Four patients are described who were treated locally with cidofovir (cream 1% or injection of 2.5 mg/ml solution) for multi-treated relapsing HPV-associated lesions. Three of the four patients had a complete response. The fourth patient showed a clinical response in the first cycle of treatment, but new lesions appeared during four successive cycles of cidofovir.
Recently, we have demonstrated that T30695, a G-tetrad-forming oligonucleotide, is a potent inhibitor of human immunodeficiency virus, type I (HIV-1) integrase and the K(+)-induced loop folding of T30695 plays a key role in the inhibition of HIV-1 integrase (Jing, N., and Hogan, M. E. (1998) J. Biol. Chem. 273, 34992-34999). Here we have modified T30695 by introducing a hydrophobic bulky group, propynyl dU, or a positively charged group, 5-amino dU, into the bases of T residues of the loops, and by substitution of the T-G loops by T-T loops. Physical measurements have demonstrated that the substitution of propynyl dU or 5-amino dU for T in the T residues of the loops did not alter the structure of T30695, and these derivatives also formed an intramolecular G-quartet structure, which is an essential requirement for anti-HIV activity. Measured IC(50) and EC(50) values show that these substitutions did not induce an apparent decrease in the ability to inhibit HIV-1 integrase activity and in the inhibition of HIV-1 replication in cell culture. However, the substitution of T-T loops for T-G loops induced a substantial decrease in both thermal stability and anti-HIV activity. The data analysis of T30695 and the 21 derivatives shows a significant, functional correlation between thermal stability of the G-tetrad structure and the capacity to inhibit HIV-1 integrase activity and between thermal stability of the G-tetrad structure and the capacity to inhibit HIV-1 replication, as assessed with the virus strains HIV-1 RF, IIIB, and MN in cell culture. This relationship between thermostability and activity provides a basis for improving the efficacy of these compounds to inhibit HIV-1 integrase activity and HIV-1 replication in cell culture.
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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This review article presents the fourth part (part D) in the series of stories on antiviral drug discovery. The stories told in part D focus on: (i) the cyclotriazadisulfonamide compounds; (ii) the {5-[(4-bromophenylmethyl]-2-phenyl-5H-imidazo[4,5-c]pyridine} compounds; (iii) (1H,3H-thiazolo[3,4-a]benzimidazole) derivatives; (iv) T-705 (6-fluoro-3-hydroxy-2-pyrazinecarboxamide) and (v) its structurally closely related analogue pyrazine 2-carboxamide (pyrazinamide); (vi) new strategies for the treatment of hemorrhagic fever virus infections, including, as the most imminent, (vii) dengue fever, (viii) the veterinary use of acyclic nucleoside phosphonates; (ix) the potential (off-label) use of cidofovir in the treatment of papillomatosis, particularly RRP (recurrent respiratory papillomatosis); and (x) finally, the prophylactic use of tenofovir to prevent HIV infections.
No abstract is provided for this article.
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.
