Inhibition of HIV-1 by a peptide ligand of the genomic RNA packaging signal Psi

The interaction of the nucleocapsid NCp7 of the human immunodeficiency virus type 1 (HIV-1) Gag polyprotein with the RNA packaging signal Psi ensures specific encapsidation of the dimeric full length viral genome into nascent virus particles. Being an essential step in the HIV-1 replication cycle, specific genome encapsidation represents a promising target for therapeutic intervention. We previously selected peptides binding to HIV-1 Psi-RNA or stem loops (SL) thereof by phage display. Herein, we describe synthesis of peptide variants of the consensus HWWPWW motif on membrane supports to optimize Psi-RNA binding. The optimized peptide, psi-pepB, was characterized in detail with respect to its conformation and binding properties for the SL3 of the Psi packaging signal by NMR and tryptophan fluorescence quenching. Functional analysis revealed that psi-pepB caused a strong reduction of virus release by infected cells as monitored by reduced transduction efficiencies, capsid p24 antigen levels, and electron microscopy. Thus, this peptide shows antiviral activity and could serve as a lead compound to develop new drugs targeting HIV-1.     

Effects of carbon fillers on the thermal conductivity of highly filled liquid‐crystal polymer based resins

The thermal conductivity of insulating polymers can be increased by the addition of conductive fillers. One potential market for these thermally conductive resins is for fuel cell bipolar plates. In this study, various amounts of three different carbon fillers (carbon black, synthetic graphite particles, and carbon fiber) were added to Vectra A950RX liquid crystal polymer. Because the resulting composites were anisotropic, they were tested for both through‐plane and in‐plane thermal conductivities. The effects of single fillers and combinations of the different fillers were studied via a factorial design. Each single filler caused a statistically significant increase in composite through‐plane and in‐plane thermal conductivities at the 95% confidence level, with synthetic graphite causing the largest increase. All of the composites containing combinations of the different fillers caused statistically significant increases in the composite through‐plane and in‐plane thermal conductivities. It is possible that thermally conductive pathways were formed that linked these carbon fillers, which resulted in increased composite thermal conductivity. Composites containing 70, 75, and 80 wt % synthetic graphite and the composite containing all three fillers (2.5 wt % carbon black, 65 wt % synthetic graphite, and 5 wt % carbon fiber) had in‐plane thermal conductivities of 20 W m^?1 K^?1 or higher, which is desirable for bipolar plates. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Interaction between amino acid degradation,sensory attributes and lipid peroxidation in wheat rolls

The influence of lipid peroxidation and heating duration on the amino acid pattern of wheat rolls was assessed in a model baking test. Therefore, three different types of dough were prepared including dough without any fat and two doughs with fat. To estimate the impact of lipid peroxidation products on the amino acid pattern, the two doughs containing fat were both made with rapeseed oil, one with fresh oil, the other with oxidised rapeseed oil. All kinds of dough were baked for three different duration times (18, 24 and 30 min). The lipid peroxidation status of both rapeseed oils was measured with the peroxide value and the p‐anisidine value of the unbaked fat. The amino acid content was analysed by HPLC after acid and alkaline hydrolysis. Besides determining water content and protein content, a sensory analysis was performed. Whereas the amino acid content in the dough without fat was only affected by the baking time, the doughs with rapeseed oil additionally showed a significant increase in amino acid degradation caused by lipid peroxidation products. Especially in the dough prepared with oxidised rapeseed oil, the amino acid content was partly decreased in raw dough without any heating influence. Confirming the influence of lipid peroxidation products in dough prepared with oxidised rapeseed oil, sensory analysis also showed the significantly worst overall score.     

Partial purification and characterization of acylester hydrolase from Lupinus mutabilis

An alkaline acylester hydrolase was partially purified from germinated seeds of Lupinus mutabilis. Hydrolytic activity was absent in the crude extract of ungerminated lupine seed, but it increased and peaked at the fourth day in the germinating seedling. The purification scheme involved homogenization, centrifugation, acetone precipitation, anion exchange chromatography, pH precipitation, and hydrophobic interaction chromatography. The acylester hydrolase was purified 126-fold, and the overall activity yield was 10%. The molecular weight estimated by sodium dodecylsulfate-polyacrylamide gel electrophoresis was 60 kDa. The enzyme had an isoelectric point of 6.2 and showed maximal activity at pH 8.0. The enzyme showed good stability between pH 5.0 and 9.0. In the pH range 7.0–7.5, enzyme precipitation was observed. The enzyme was stable from 0 to 25°C for 5 h and at 45°C lost 50% of its activity in the same period of time. At higher temperatures, the enzyme showed low thermal stability. However, the highest initial activity was found to be at 45°C. Nonionic surfactants and cholic acid enhanced the activity of the enzyme. The activity was reduced by the addition of toluene and isooctane and increased by the addition of diethyl ether, acetonitrile, methanol, and pyridine. The activity was reduced by 37% in the presence of 1 mM Cu²⁺ ions. The enzyme-hydrolyzed triolein showing no positional specificity.     

Modelling and simulation of local mechanical properties of high silicon solution-strengthened ferritic compacted graphite iron

This study focuses on the modelling and simulation of local mechanical properties of compacted graphite iron cast at different section thicknesses and three different levels of silicon, ranging from about 3.6% up to 4.6%. The relationship between tensile properties and microstructure is investigated using microstructural analysis and statistical evaluation. Models are generated using response surface methodology, which reveal that silicon level and nodularity mainly affect tensile strength and 0.2% offset yield strength, while Young′s modulus is primarily affected by nodularity. Increase in Si content improves both the yield and tensile strength, while reduces elongation to failure. Furthermore, mechanical properties enhance substantially in thinner section due to the high nodularity. The obtained models have been implemented into a casting process simulation, which enables prediction of local mechanical properties of castings with complex geometries. Very good agreement is observed between the measured and predicted microstructures and mechanical properties, particularly for thinner sections.     

Spezifische Bedarfe bei zahnärztlichen Patienten mit Demenz und ihre ethischen Implikationen

Definition of the problem

The central foundations of successful dental treatment consist of a trustful patient-dentist relationship, the professional and psychosocial expertise of the team treating the patient, and consideration of ethical aspects both during the therapeutic decision-making process and during the subsequent execution of therapy. This is especially true of the dental treatment of (mostly elder) persons with dementia, calling for an in-depth assessment of the various normative implications.

Arguments

In geriatric dentistry in particular, situational dilemmas regarding treatment often arise from specific constellations (e.?g. greatly reduced potential for dental therapy, lack of ability regarding oral hygiene and lack of individual patient responsibility) combined with an acute need for treatment and the necessary involvement of third parties. These dilemmas frequently place additional professional and normative demands on the dentist. The current contribution discusses this specific situation, first by way of theoretical discourse and subsequently with a case-related approach on the basis of two case histories.

Conclusion

It becomes clear here that classic state-of-the-art therapies are replaced by “compromise treatment” in many cases in geriatric dentistry. Such treatment follows divergent diagnostic and therapeutic rules, poses changed requirements in terms of communication and presents specific ethical challenges and pitfalls.

     

Influence of processing parameters on quality factors of one-shot hybrid structures made by RTM

This paper is dealing with the influence of processing parameters for manufacturing of steel–carbon-fiber-reinforced-plastic (CFRP) hybrid plates by using the one-shot-hybrid resin-transfer-moulding (OSH-RTM) process. A design of experiments study was carried out. The quality of the manufactured parts was quantified by the bending modulus, the apparent interlaminar shear strength (ILSS), the maximum deflection and the density of the CFRP. The following changeable processing parameters were chosen: mould temperature, resin temperature, change in mass flow and maximum injection pressure. It is shown that the mould temperature and the change in mass flow show significant impact on the flexural modulus, density and maximum deflection of the plate while there is no significant impact on the apparent ILSS. Furthermore, the interaction between the mould temperature and resin temperature is having an influence on the flexural modulus and density.     

Enhanced wear performance of nylon 6/organoclay nanocomposite by blending with a thermotropic liquid crystalline polymer

A new approach for improving the wear performances of nylon 6 (PA6)/clay nanocomposites was examined in this study. Two hybrid nanocomposites were prepared by melt blending a thermotropic liquid crystalline polymer (TLCP) and a well‐dispersed PA6/clay nanocomposite, but with and without the incorporation of maleic‐anhydride grafted polypropylene (MAPP) as compatibilizer. The addition of MAPP improved the compatibility between TLCP and matrix and thus enhanced the fibrillation of dispersed TLCP phase. Wear‐testing results revealed that the wear resistance of the compatibilized hybrid nanocomposite could be improved effectively, as indicated by the low values of specific wear rate and frictional coefficient, especially under high‐normal load (i.e., 80 N). Based on the characterization on the worn damage and the debris, it was suggested that abrasive wear was the main‐damage mechanism for all the materials under investigation, except for the compatibilized hybrid nanocomposite. For this system, the wear damage was caused by a combination of abrasive and adhesive wearing because of the formation of transfer film on the counter pin surface from the wear debris. POLYM. ENG. SCI., 2010. © 2009 Society of Plastics Engineers     

Selective Pharmacophore Models of Dopamine D1 and D2 Full Agonists Based on Extended Pharmacophore Features

This study is focused on the identification of structural features that determine the selectivity of dopamine receptor agonists toward D₁ and D₂ receptors. Selective pharmacophore models were developed for both receptors. The models were built by using projected pharmacophoric features that represent the main agonist interaction sites in the receptor (the Ser residues in TM5 and the Asp in TM3), a directional aromatic feature in the ligand, a feature with large positional tolerance representing the positively charged nitrogen in the ligand, and sets of excluded volumes reflecting the shapes of the receptors. The sets of D₁ and D₂ ligands used for modeling were carefully selected from published sources and consist of structurally diverse, conformationally rigid full agonists as active ligands together with structurally related inactives. The robustness of the models in discriminating actives from inactives was tested against four ensembles of conformations generated by using different established methods and different force fields. The reasons for the selectivity can be attributed to both geometrical differences in the arrangement of the features, e.g., different tilt angels of the π system, as well as shape differences covered by the different sets of excluded volumes. This work provides useful information for the design of new D₁ and D₂ agonists and also for comparative homology modeling of D₁ and D₂ receptors. The approach is general and could therefore be applied to other ligand–protein interactions for which no experimental protein structure is available.     

Inhibition of Human DHODH by 4‐Hydroxycoumarins,Fenamic Acids,and N‐(Alkylcarbonyl)anthranilic Acids Identified by Structure‐Guided Fragment Selection

A strategy that combines virtual screening and structure‐guided selection of fragments was used to identify three unexplored classes of human DHODH inhibitor compounds: 4‐hydroxycoumarins, fenamic acids, and N‐(alkylcarbonyl)anthranilic acids. Structure‐guided selection of fragments targeting the inner subsite of the DHODH ubiquinone binding site made these findings possible with screening of fewer than 300 fragments in a DHODH assay. Fragments from the three inhibitor classes identified were subsequently chemically expanded to target an additional subsite of hydrophobic character. All three classes were found to exhibit distinct structure–activity relationships upon expansion. The novel N‐(alkylcarbonyl)anthranilic acid class shows the most promising potency against human DHODH, with IC₅₀ values in the low nanomolar range. The structure of human DHODH in complex with an inhibitor of this class is presented.