Publications

Selective Laser Melting (SLM) is an Additive Manufacturing (AM) technique in which a part is built up in a layer- by-layer manner by melting the top surface layer of a powder bed with a high intensity laser according to sliced 3D CAD data. In this work, mechanical properties like tensile strength, elongation, Young's modulus, impact toughness and hardness are investigated for SLM-produced AlSi10Mg parts, and compared to conventionally cast AlSi10Mg parts. It is shown that AlSi10Mg parts with mechanical properties comparable or even exceeding to those of conventionally cast AlSi10Mg can be produced by SLM.

Abstract We have demonstrated that thymidylate synthase (TS) activity is enhanced by more than 10- to 20-fold in HCMV-infected HEL cells as compared to non-infected cells. The increase in TS activity was found (i) to parallel the progression of the viral cytopathic effect over a 5-days period, (ii) to be independent of viral DNA synthesis and to result from an early event in the viral replicative cycle. Several compounds known to be targeted at TS, such as 5-fluoro-dUrd, 5-trifluoromethyl-dUrd, and 5-formyl-dUrd, inhibited TS activity in HCMV-infected cells and, concomitantly, displayed HCMV activity. The exact impact of inhibition of TS activity in the overall anti-HCMV activity of the test compounds remains however to be determined.

sponsorship: The authors acknowledge the kind help of Mr. A. Madhukar Reddy, Secretary and Correspondent, S.R. College of Pharmacy, Warangal, India for providing laboratory facilities for the present research work and the technical assistance of Mrs. Leentje Persoons, Mrs. Lies Van den Heurck, Mr. Steven Carmans and Mrs. Anita Camps was greatly appreciated. The antiviral/cytostatic assays were supported by the KU Leuven (GOA 10/14). (KU Leuven|GOA 10/14)

In order to obtain the high accuracy required for a metrological atomic force microscope, the sample approach mechanism meets strict specifications. The design presented in this paper offers a stiff construction, which limits the influences of floor vibrations on the measurement. Next to this, thermal considerations in the design decrease the uncertainties introduced by temperature variations of the environment. Uncertainties can also be caused by misalignment of the sample holder with respect to the measurement system of three interferometers. To limit these uncertainties, the approach mechanism provides sufficient alignment possibilities. The performance of the sample approach mechanism was evaluated by means of a finite element simulation of its dynamic stiffness. A series of experiments provide the unknown parameters to the simulation model. The dynamic stiffness lies around 395Hz, which is sufficiently high to provide accurate measurements.

Abstract For Abstract see ChemInform Abstract in Full Text.

Human immunodeficiency virus (HIV) reverse transcriptase (RT)-associated ribonuclease H (RNase H) remains as the only enzyme encoded within the viral genome not targeted by current antiviral drugs. In this work, we report the design, synthesis, and biologic evaluation of a novel series of galloyl derivatives with HIV-1 RNase H inhibitory activity. Most of them showed IC₅₀ s at sub- to low-micromolar concentrations in enzymatic assays. The most potent compound was II-25 that showed an IC₅₀ of 0.72 ± 0.07 μM in RNase H inhibition assays carried out with the HIV-1_BH₁₀ RT. II-25 was 2.8 times more potent than β-thujaplicinol in these assays. Interestingly, II-25 and other galloyl derivatives were also found to inhibit the HIV IN strand transfer activity in vitro. Structure-activity relationships (SAR) studies and molecular modeling analysis predict key interactions with RT residues His539 and Arg557, while providing helpful insight for further optimization of selected compounds.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

To overcome the low oral bioavailability of the highly potent and selective antiretroviral agent (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA), a new lipophilic ester derivative, i.e., the bis(isopropyloxycarbonyloxymethyl)-ester [bis(POC)-PMPA], was prepared. The usefulness of bis(POC)-PMPA as an oral prodrug for PMPA was investigated in the intestinal mucosa Caco-2 cell monolayer model. The total transport of bis(POC)-PMPA was 2.7%, whereas it was less than 0.1% for PMPA. Bis(POC)-PMPA was considerably metabolized inside the epithelial cells, since the majority of the compound was recovered after transport in the form of the monoester metabolite [mono(POC)-PMPA]. In contrast, bis(POC)-PMPA was relatively resistant to degradation at the luminal side of the Caco-2 cells. Pharmacokinetic studies with mice showed that the oral bioavailability of bis(POC)-PMPA (calculated from the curves of the concentration of free PMPA in plasma) was 20%. Neither bis(POC)-PMPA nor mono(POC)-PMPA could be recovered in plasma, suggesting the efficient release of the active drug PMPA after oral administration of bis(POC)-PMPA. Severe combined immunodeficient (SCID) mice infected with Moloney murine sarcoma virus (MSV) and treated orally with bis(POC)-PMPA for 5 or 10 days (dosages, 50, 100, or 200 mg of PMPA equivalent per kg of body weight per day) showed a significant delay in MSV-induced tumor appearance and tumor-associated death. The antiviral efficacy of oral bis(POC)-PMPA was related to the dosage and treatment period and was not significantly different from that of subcutaneous PMPA given at an equivalent dose. The favorable pharmacokinetic profile, marked antiviral efficacy, and low toxicity make bis(POC)-PMPA an attractive oral prodrug of PMPA that should be further pursued in clinical studies with patients infected with human immunodeficiency virus or hepatitis B virus.