4,552 publications from this institution
Extension of P1 is very inefficient with this 6-month regimen. Operational research should define appropriate algorithms allowing an earlier switch to the next higher regimen for those in need, using follow-up smears for screening.
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.
No abstract is provided for this article.
No abstract is provided for this article.
Bicyclams are low-molecular-weight anti-human immunodeficiency virus (HIV) agents that have been shown to act as potent and selective CXC chemokine receptor 4 (CXCR4) antagonists. Here, we demonstrate that bicyclams are potent inhibitors of feline immunodeficiency virus (FIV) replication when evaluated in Crandell feline kidney (CRFK) cells. With a series of bicyclam derivatives, 50% inhibitory concentrations (IC50s) against FIV were obtained in this cell system that were comparable to those obtained for HIV-1 IIIB replication in the human CD4(+) MT-4 T-cell line. The bicyclams were also able to block FIV replication in feline thymocytes, albeit at higher concentrations than in the CRFK cells. The prototype bicyclam AMD3100, 1-1'-[1,4-phenylene-bis(methylene)]-bis(1,4,8, 11-tetraazacyclotetradecane), was only fourfold less active in feline thymocytes (IC50, 62 ng/ml) than in CRFK cells (IC50, 14 ng/ml). AMD2763, 1,1'-propylene-bis(1,4,8, 11-tetraazacyclotetradecane), which is a less potent CXCR4 antagonist, was virtually inactive against FIV in feline thymocytes (IC50, >66.5 microgram/ml), while it was clearly active in CRFK cells (IC50, 0.9 microgram/ml). The CXC chemokine stromal-cell-derived factor 1alpha had anti-FIV activity in CRFK cells (IC50, 200 ng/ml) but not in feline thymocytes (IC50, >2.5 microgram/ml). When primary FIV isolates were evaluated for their drug susceptibility in feline thymocytes, the bicyclams AMD3100 and its Zn2+ complex, AMD3479, inhibited all six primary isolates at equal potency. The marked susceptibility of FIV to the bicyclams suggests that FIV predominantly uses feline CXCR4 for entering its target cells.
3'-Azido-2',3'-dideoxythymidine (AZT) and 2',3'-didehydro-2',3'-dideoxythymidine (D4T) are potent and selective inhibitors of human immunodeficiency virus replication in MT-4 and ATH8 cells. They are also inhibitory to the replication of murine retroviruses, i.e. Moloney murine sarcoma virus-induced transformation of C3H cells. In MT-4 cells AZT is readily phosphorylated to its 5'-monophosphate, while the 5'-di- and 5'-triphosphates are generated to a 200-600-fold lower extent than the 5'-monophosphate. D4T is phosphorylated in MT-4 cells to its 5'-monophosphate at a 300-600-fold lower extent than AZT. The phosphorylation of AZT in the thymidine kinase-deficient cell line (Raji/TK-) is severely depressed, while D4T phosphorylation is only slightly diminished in Raji/TK- as compared to Raji/0 cells. D4T has a 10-fold lower affinity for phosphorylation by crude MT-4 cell extracts than AZT (Km, 142 and 14 microM, respectively), and the Vmax for phosphorylation of D4T is only 5% that of AZT. D4T is phosphorylated by MT-4 cell extracts about 180-fold less efficiently than AZT (Vmax/Km, 0.06 for D4T, as compared to 11 for AZT), and this is consistent with the differences found in the amounts of phosphorylated products of D4T and AZT formed in intact MT-4 cells. The 5'-triphosphates of AZT and D4T are equipotent in their inhibitory effects on the reverse transcriptases from human immunodeficiency virus and Moloney murine leukemia virus.
Structure-activity investigation in the series of acyclic nucleotide analogs bearing a modified phosphoric acid residue at the side-chain revealed two novel classes of antivirals: N--(3-hydroxy-2-phosphonylmethoxypropyl)- (HPMP-) and N-(2-phosphonylmethoxyethyl) (PME-) derivatives of heterocyclic bases. Adenine, guanine, 2-aminoadenine and (in the HPMP-series) cytosine derivatives act specifically against DNA viruses (herpes viruses,adenoviruses,poxviruses). The PME-compounds are also active against retroviruses (MSV,HIV)and exhibit a cytostatic effect on L-1210 mouse leukemia cells.The drugs are converted by the action of cellular nucleotide kinases into their diphosphates and inhibit viral and, to a lesser extent, cellular DNA synthesis. These metabolites exert a comparatively low inhibitory effect on viral (HSV-1) DNA polymerase. The diphosphates derived from PME-compounds strongly inhibit viral (HSV-1) ribonucleotide reductase and AMV reverse transcriptase.
