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.     

Rheological characterization of starch derivatives/polycaprolactone blends processed by reactive extrusion

Linear viscoelastic, steady shear behaviors, and morphologies of starch formate/poly(ε-caprolactone) (PCL) blends, compatibilized by oligomers and obtained by reactive extrusion, have been investigated as a function of formic acid (FA)/starch ratio, nature, and molecular weight of the oligomer. The rheological properties of these blends have been compared with those of a commercial starch-based thermoplastic, namely Mater-Bi® ZF03UA. In presence of FA, starch is destructured to starch formate and oligomers are used as plasticizers. The linear viscoelastic response of blends is quite similar to that of nanocomposite materials: the low frequency behavior is attributed to a percolated network of destructured starch particles, and the high frequency behavior is that of the polymer matrix. The viscosity curve presents a profile characterized by two plateau regions, at low and high shear rates. The plateau region at low shear rates corresponds to the viscous response of the blend while that observed at high shear rates can be attributed to the PCL matrix. The compatibilization is enhanced in the presence of starch formate and increases with increasing the oligomer molecular weight. The use of PCL oligomer was shown to improve this compatibilization effect. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers     

An experimental investigation of gas-liquid two-phase flow in single microchannel contactors

This paper describes two-phase flow pattern and pressure drop characteristics during the absorption of CO₂ into water in three horizontal microchannel contactors which consist of Y-type rectangular microchannels having hydraulic diameters of 667, 400 and , respectively. With the help of a high-speed photography system, flow patterns such as bubbly flow, slug flow (including two sub-regimes, Taylor flow and unstable slug flow), slug-annular flow, churn flow and annular flow were observed in these microchannels. The applicability of the currently available correlations for describing flow pattern transitions in microchannels has been examined. Generally, the predicting performance of these correlations deteriorates as the channel diameter further reduces. Toward solving this discrepancy, an empirical correlation based on the superficial Weber numbers was developed to interpret the transition from Taylor flow to unstable slug flow in three microchannels. Taylor bubble formation process in microchannels was found to be in the squeezing regime at lower superficial liquid velocities (Ca ranging from 0.0019 to 0.029) while the transition to the dripping regime was observed at the highest superficial liquid velocity of 1.0 m/s. Lengths of Taylor bubbles formed in the squeezing regime can be well represented by the scaling relation proposed by Garstecki et al. [Formation of droplets and bubbles in a microfluidic T-junction—scaling and mechanism of break-up. Lab on a Chip, 6, 437-446]. For flow patterns including slug-annular flow, annular flow and churn flow, a simple analysis based on the separated flow model has been performed in order to reveal the observed effect of the superficial liquid velocity on two-phase frictional multiplier in the present microchannels. Then, reasonable correlations for the prediction of two-phase frictional pressure drop under these flow patterns were suggested.     

Refining Genotypes and Phenotypes in KCNA2-Related Neurological Disorders

Pathogenic variants in KCNA2, encoding for the voltage-gated potassium channel K_v1.2, have been identified as the cause for an evolving spectrum of neurological disorders. Affected individuals show early-onset developmental and epileptic encephalopathy, intellectual disability, and movement disorders resulting from cerebellar dysfunction. In addition, individuals with a milder course of epilepsy, complicated hereditary spastic paraplegia, and episodic ataxia have been reported. By analyzing phenotypic, functional, and genetic data from published reports and novel cases, we refine and further delineate phenotypic as well as functional subgroups of KCNA2-associated disorders. Carriers of variants, leading to complex and mixed channel dysfunction that are associated with a gain- and loss-of-potassium conductance, more often show early developmental abnormalities and an earlier onset of epilepsy compared to individuals with variants resulting in loss- or gain-of-function. We describe seven additional individuals harboring three known and the novel KCNA2 variants p.(Pro407Ala) and p.(Tyr417Cys). The location of variants reported here highlights the importance of the proline(405)–valine(406)–proline(407) (PVP) motif in transmembrane domain S6 as a mutational hotspot. A novel case of self-limited infantile seizures suggests a continuous clinical spectrum of KCNA2-related disorders. Our study provides further insights into the clinical spectrum, genotype–phenotype correlation, variability, and predicted functional impact of KCNA2 variants.     

Aspects of kinetic modeling of fixed bed reactors

This paper briefly reviews the most important aspects of catalyst testing in packed-bed catalytic laboratory reactors to properly assess the intrinsic chemical kinetics. Next it discusses approaches to assess the kinetics of fast reactions or those accompanied with strong heat effects that cannot be performed in a packed-bed reactor configuration free from transport limitations. As an example the partial oxidation of methane is presented in a steady-state fixed bed reactor as well as in a TAP (temporal analysis of products) reactor. The continuing increase in computational power leads to more sophisticated reaction and reactor models due to the increasing use of computational chemistry and computational fluid dynamics in reaction engineering.     

Air impingement and intermittent drying: Application to apple and to mango

An original drying process combining air impingement and intermittent drying was studied on apple slices and mango cubes. The influence of four operating parameters (air velocity, drying/tempering periods, upper height, and air temperature) on the drying time and on the drying rate was evaluated. Continuous and intermittent drying were compared. The intermittency α = 1/7 (τ_on = 10 seconds and τ_off = 60 seconds) gave the best results. A time savings of 54% for apple and 67% for mango was reached. In continuous drying, a time savings of 4620 seconds was observed by increasing the air velocity from 6 to 40 m s^?1 for apple. Air temperatures of 328 K for apple and of 328 K or 338 K for mango were determined as optimum to prevent case‐hardening. Experimental results were fitted with the analytical solution of Fick's second law and the modified Page equation (average values R² = 0.985 and 0.961, for apple and mango, respectively). For both products, the apparent moisture diffusivity D_app, the drying constant k, the drying coefficient n, and the activation energy E_a, were identified. Activation energies calculated from the analytical solution were 30.3 and 36.8 kJ mol^?1 and were 25.4 and 30.0 kJ mol^?1 using the modified Page equation for apple and mango, respectively. Mango has an increased temperature sensitivity and thus will need less energy for drying than apple.     

Mass Spectrometry-Based Proteomics Reveal Alcohol Dehydrogenase 1B as a Blood Biomarker Candidate to Monitor Acetaminophen-Induced Liver Injury

Acute liver injury (ALI) is a severe disorder resulting from excessive hepatocyte cell death, and frequently caused by acetaminophen intoxication. Clinical management of ALI progression is hampered by the dearth of blood biomarkers available. In this study, a bioinformatics workflow was developed to screen omics databases and identify potential biomarkers for hepatocyte cell death. Then, discovery proteomics was harnessed to select from among these candidates those that were specifically detected in the blood of acetaminophen-induced ALI patients. Among these candidates, the isoenzyme alcohol dehydrogenase 1B (ADH1B) was massively leaked into the blood. To evaluate ADH1B, we developed a targeted proteomics assay and quantified ADH1B in serum samples collected at different times from 17 patients admitted for acetaminophen-induced ALI. Serum ADH1B concentrations increased markedly during the acute phase of the disease, and dropped to undetectable levels during recovery. In contrast to alanine aminotransferase activity, the rapid drop in circulating ADH1B concentrations was followed by an improvement in the international normalized ratio (INR) within 10–48 h, and was associated with favorable outcomes. In conclusion, the combination of omics data exploration and proteomics revealed ADH1B as a new blood biomarker candidate that could be useful for the monitoring of acetaminophen-induced ALI.     

Interlinking Music-Related Data on the Web

This article describes how Semantic Web technologies can be used to interlink musical data sources that have traditionally been isolated and difficult to integrate.     

Development of an experimental technique to assess the permeability of metal coated polymer films

The experimental time required to measure water vapour permeability of barrier film using the cup method is extremely long. In this study, a new technique is proposed, based on light transmission. This fast and accurate method was first validated using model films constituted of aluminized PET (polyethylene terephthalate) with aluminium layers of different thicknesses (<100 nm). It was possible to show that the ‘illuminating’ method could advantageously be employed to control the film’s barrier properties during their fabrication. In a second step, the method was tentatively used to measure the changes in barrier properties over time, when the samples are submitted to severe hydrothermal ageing (70 °C, 90% relative humidity [RH]). It was concluded that the complex degradation mechanism prevents accurate measurement while ageing.