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Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The first members of a new family of heterocarbobicyclic nucleoside analogues have been synthesized from the cis/trans mixture of (4-amino-5,6-dihydro-4H-cyclopenta[b]thiophen-6-yl)methanols (cis/trans -7). The separation of the cis and trans intermediates during the preparation of the 6-chloropurine derivatives allowed a separate preparation of the purine heterocarbanucleosides cis-10 and trans-11, from which cis-12-14 and trans-16-18 were obtained by replacement of the 6-chloro substituent with amino, hydroxy, and cyclopropylamino groups. Additionally, the 6-phenylpurinyl analogues cis-15 and trans- 19 were prepared from cis-10 and trans-11 using Suzuki-Miyaura methodology. In tests of antiviral and cytostatic activities, compound 11 showed cytostatic activity against Molt4/C8 human T lymphoblastic leukemia cells. Antiviral activity was shown by compounds 15 and 19 against Punta­ Toro virus and Coxackie virus B4 (compound 11).

The relationship between adherence, virological response to highly active antiretroviral therapy (HAART) and the presence and development of genotypic resistance was assessed in 41 HIV-infected patients on HAART. Four adherence parameters (drug taking adherence, dosing adherence, timing adherence and drug holidays) were scored prospectively using electronic event monitoring. Genotypic resistance at baseline and after therapy failure was scored retrospectively and a genotype-based susceptibility score was calculated. Overall median adherence rates were high. All adherence parameters were better in virological responders (n=31) compared to non-responders (n=10), drug taking adherence and number of drug holidays being significantly different. Responders had a significantly higher susceptibility score. Stepwise logistic regression showed that the number of drug holidays and a low susceptibility score were highly predictive for therapy failure. Despite the presence of a limited number of baseline resistance mutations, perfectly adherent patients can control virus replication for a prolonged period.

The 5'-azidonucleosides 3 and 4 were obtained by treating thymidine and 2'-deoxyuridine with TPP/DEAD/HN3. The 3'-O-silylated 5'-azido-5'-deoxythymidine 5 and the corresponding 2'-deoxyuridine derivative 6 were transformed to the formamides (7 and 8, respectively) and dehydrated to the protected 5'-isocyano derivatives 9 and 10; deblocking gave 5'-isocyano-5'-deoxythymidine (11) and 5'-isocyano-2',5'-dideoxyuridine (12). 2,3'-Anhydro-5'-formamido derivatives of thymidine and 2'-deoxyuridine (19 and 20, respectively) were prepared by three different ways. In the most direct synthesis 3 and 4 were transformed to the 2,3'-anhydro-5'- azidonucleosides 17 and 18 by using TPP/DEAD; following the reaction with TPP/HCO2COCH3 gave 19 and 20. Nucleophilic opening reaction with LiN3 yielded the 3'-azido-5'-formylamino derivatives 21 and 22. Dehydration to 3'-azido-5'-isocyano-3',5'-dideoxythymidine (23) and 3'-azido-5'-isocyano-2',3',5'-trideoxyuridine (24) was achieved with tosyl chloride/pyridine. In contrast with 3'-azido-3'-deoxythymidine, compounds 11, 12, 23, and 24 were devoid of any marked inhibitory effect against DNA and RNA viruses including human immunodeficiency virus type I (HIV).

Human immunodeficiency virus type 1 (HIV-1) uses the chemokine receptors CCR5 and CXCR4 as coreceptors for entry. It was recently demonstrated that HIV-1 glycoprotein 120 (gp120) elevated calcium and activated several ionic signaling responses in primary human macrophages, which are important targets for HIV-1 in vivo. This study shows that chemokine receptor engagement by both CCR5-dependent (R5) and CXCR4-dependent (X4) gp120 led to rapid phosphorylation of the focal adhesion-related tyrosine kinase Pyk2 in macrophages. Pyk2 phosphorylation was also induced by macrophage inflammatory protein-1beta (MIP-1beta) and stromal cell-derived factor-1alpha, chemokine ligands for CCR5 and CXCR4. Activation was blocked by EGTA and by a potent blocker of calcium release-activated Ca++ (CRAC) channels, but was insensitive to pertussis toxin (PTX), implicating CRAC-mediated extracellular Ca++ influx but not Galpha(i) protein-dependent mechanisms. Coreceptor engagement by gp120 and chemokines also activated 2 members of the mitogen-activated protein kinase (MAPK) superfamily, c-Jun amino-terminal kinase/stress-activated protein kinase and p38 MAPK. Furthermore, gp120-stimulated macrophages secreted the chemokines monocyte chemotactic protein-1 and MIP-1beta in a manner that was dependent on MAPK activation. Thus, the gp120 signaling cascade in macrophages includes coreceptor binding, PTX-insensitive signal transduction, ionic signaling including Ca++ influx, and activation of Pyk2 and MAPK pathways, and leads to secretion of inflammatory mediators. HIV-1 Env signaling through these pathways may contribute to dysregulation of uninfected macrophage functions, new target cell recruitment, or modulation of macrophage infection.

Layerwise Laser Melting (LLM) is a layerwise production technique enabling the production of complex metallic parts. Thin powder layers are molten according to a predefined scan pattern by means of a laser source. Nowadays constant process parameters are used throughout the build, leading for some geometries to an overly thick feature size or overheating at downfacing surfaces. In this paper a monitoring and control system is presented which enables monitoring the melt pool continously at high speed throughout the building process. The signals from the sensors can be incorporated in a real-time control loop, in this way enabling feedback control of the process parameters. In this paper the experimental set-up will be first shown. Next the dynamic relation between the melt pool and the process parameters is identified. Finally the proof of concept for feedback control is demonstrated with experimental results.