Pseudopeptide TASP inhibitors of HIV entry bind specifically to a 95-kDa cell surface protein

The template assembled synthetic peptide constructs (TASP), pentavalently presenting the tripeptide KPR or RPK, are potent and specific inhibitors of human immunodeficiency virus (HIV) infection by preventing viral entry into permissive cells. Here the 5[KPsi(CH2N)PR]-TASP construct, Psi(CH2N) for reduced peptide bond, was used in studies to demonstrate its specific binding to a 95-kDa cell surface protein ligand. Compared to its nonreduced 5[KPR]-TASP counterpart, the pseudopeptide 5[KPsi(CH2N)PR]-TASP manifested higher affinity to bind to its cell surface ligand, increased activity to inhibit HIV infection, and resistance to degradation when incubated in serum from an HIV-1 seropositive individual. In ligand blotting experiments, the biotin-labeled 5[KPsi(CH2N)PR]-TASP identified a single 95-kDa protein in crude cell extracts. This 95-kDa protein (p95) is expressed on the cell surface since surface iodination of cells resulted in its labeling, and moreover, following incubation of cells with the biotin-labeled 5[KPsi(CH2N)PR]-TASP, the p95.TASP complex was recovered by affinity chromatography using avidin-agarose. All anti-HIV TASP constructs but not their control derivatives affected the binding of biotin-labeled 5[KPsi(CH2N)PR]-TASP to p95, thus emphasizing the specific nature of this binding. Since 5[KPsi(CH2N)PR]-TASP does not interact with HIV-envelope glycoproteins, our results suggest that TASP inhibitors mediate directly or indirectly a block in HIV-mediated membrane fusion process by binding to the cell surface expressed p95.     

Alcohol and benzodiazepines: recent mechanistic studies

The phospholipid headgroup mobility of small unilamellar vesicles composed of different mixtures of phosphatidyl-L-serine (PS) and phosphatidylcholine is characterized by the solvent relaxation behavior of the polarity sensitive dyes 6-propionyl-2-(dimethylamino)naphthalene (Prodan) and 6-palmitoyl-2-[trimethylammoniumethyl]-methylamino]naphthalene chloride (Patman). If the PS content exceeds 10%, the addition of calcium leads to a substantial deceleration of the solvent relaxation of both dyes, indicating the formation of Ca(PS)2 complexes. Addition of prothrombin and its fragment 1 leads to a further decrease of the headgroup mobility, as explained by the binding of more than two PS-molecules by a single protein molecule. Prodan monitors the outermost region of the bilayer and it clearly distinguishes between the binding of prothrombin and its fragment 1. The deeper incalated Patman does not distinguish between both proteins. The validity of the solvent relaxation technique for the investigation of the membrane binding of peripheral proteins is demonstrated by the studies of prothrombin induced changes in the steady-state fluorescence anisotropies of 1,6-diphenyl-1,3, 5-hexatriene.     

Synthesis and characterization of ruthenium dioxide nanostructures

We report the synthesis of ruthenium dioxide (RuO₂) nanostructures by thermal evaporation of RuO₂ powder. RuO₂ nanostructures of different shapes were synthesized at various concentration, flow rate, and pressure of oxygen. At a constant pressure of 3 torr of flowing oxygen, polygonal prism-like RuO₂ nanorods with flat tips were grown at an O₂ flow rate of 100 sccm; club-shaped nanorods with obelisk tip were formed at 300 and 600 sccm, and hollow rods with square tip were formed at 1800 sccm. A mixture of O₂ and Ar at a total flow rate of 600 sccm led to the formation of short club-shaped nanorods indicating the suppression effect of Ar on the growth of nanorods. The pressure also had a significant effect on the formation of RuO₂ nanostructures, at a fixed flow rate of 600 sccm of O₂, a pressure of 3 torr resulted in the growth of club-shaped RuO₂ nanorods, while high pressures of 380 and 760 torr resulted in the formation of both linear club-shaped and pine tree-like hierarchical RuO₂ nanorods. X-ray diffraction and transmission electron microscopy analysis indicated the formation of tetragonal phase of RuO₂ with high crystallinity. A density functional calculation on RuO₂, RuO₃, and RuO₄ was performed to help to explain the experimental results.     

Coherent lightwave transmission at 2 Gbit/s over 170 km of optical fibre using phase modulation

We report coherent lightwave transmission at a data rate of 2Gbit/s over 170 km of optical fibre. Phase modulation is employed, and a bit error rate lower than 10-9 is achieved. The receiver sensitivity of ?39.0 dBm 10-9 BER) is an improvement of 2.4 dB over the best previously published direct-detection result for non-return-to-zero transmission.     

Primary endobronchial non-hodgkins lymphoma: description of a case and review of the literature]

Photosensitive epilepsy is relatively rare. However, a large proportion of individuals with epilepsy perceive that they are at an increased risk of a seizure whilst exposed to specific photic material. The difference between perceived and real risk may be due to inadequate education and misinformation. One half of the participants in the present survey could not recall being informed of the result of the 'gold standard' test for photosensitivity--intermittent photic stimulation during an electroencephalogram. Furthermore, approximately one-third of our sample were apparently given inaccurate and overcautious advice about their everyday exposure to photic material. Better information and advice is crucial to improve this situation in the future. The majority of people with epilepsy (>95%) who are not photosensitive can pursue activities that involve flickering or patterned light, encompassing educational, employment and leisure opportunities, without undue concern.     

Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors

Volatile anaesthetics have historically been considered to act in a nonspecific manner on the central nervous system. More recent studies, however, have revealed that the receptors for inhibitory neurotransmitters such as gamma-aminobutyric acid (GABA) and glycine are sensitive to clinically relevant concentrations of inhaled anaesthetics. The function of GABA(A) and glycine receptors is enhanced by a number of anaesthetics and alcohols, whereas activity of the related GABA rho1 receptor is reduced. We have used this difference in pharmacology to investigate the molecular basis for modulation of these receptors by anaesthetics and alcohols. By using chimaeric receptor constructs, we have identified a region of 45 amino-acid residues that is both necessary and sufficient for the enhancement of receptor function. Within this region, two specific amino-acid residues in transmembrane domains 2 and 3 are critical for allosteric modulation of both GABA(A) and glycine receptors by alcohols and two volatile anaesthetics. These observations support the idea that anaesthetics exert a specific effect on these ion-channel proteins, and allow for the future testing of specific hypotheses of the action of anaesthetics.     

Identification of a salivary vasodilator in the primary North American vector of bluetongue viruses, Culicoides variipennis

OBJECTIVE: To explore how the commonsense understanding, that those with a mental illness are dangerous, is deployed in a small sample of print media. METHOD: The print media sample was subjected to a discourse analysis informed by knowledge of media practices. Materials were read closely and references to mental illness were identified, classified and analysed. RESULTS: This non-sensational material was shown to provide repeated confirmations of the commonsense understanding that mental illnesses make people unpredictable and dangerous. Close study of the lead article suggested that it was written so that readers had to draw on such understandings to make sense of the account it presented. CONCLUSION: The study challenges the notion that media present negative depictions of mental illnesses either because journalists are poorly informed or because 'sensation sells'. It is concluded that media practices directed at engaging readers require the use of cases and a style of writing that forces readers to draw upon commonsense knowledge of mental illness to understand the text. It is argued that this is a deliberate effort to enlist readers as co-creators of the text and thereby increase their interest.     

Computational Intelligence Methods for Time Series Analysis and Forecasting: Special Issue of IWANN 2017

Neural Processing Letters - Incorporation of new knowledge into neural networks with simultaneous preservation of the previous knowledge is known to be a nontrivial problem. This problem becomes...     

Partial Characterization of Ultrafiltrated Soy Protein Hydrolysates with Antioxidant and Free Radical Scavenging Activities

Soy protein isolate (SPI) was hydrolyzed with Flavourzyme® (SHF) or chymotrypsin (SHC). Hydrolysates were sequencially fractionated by ultrafiltration using different membrane pore sizes (50, 10, and 3 kDa). The antioxidant ability of each hydrolysate protein fraction was tested in a liposome oxidizing system and their free radical scavenging activity (FRSA) was evaluated with the DPPH method (diphenylpicrilhydrazine radical). Molecular weight (MW) distribution, solubility, surface hydrophobicity, and amino acid composition of each SPI hydrolysate fraction were measured and their effect on antioxidant and scavenging activities was established by multivariate correlation. The most active ultrafiltrated peptide fractions (P < 0.05), from SHF and SHC, had of MW of <3 kDa (F3 and C3, respectively). These fractions decreased liposome oxidation by 83.2% and 84.5%, respectively, and also showed the highest FRSA (F3: 21.3% and C3: 24.4%). In addition to molecular size, the antioxidant activity and FRSA of soy protein fractions were related to their amino acid composition, especially to an increased content of Phe and a lowered content of Lys. Also, hydrophobicity of ultrafiltrated peptide fractions was an important characteristic (P < 0.001) associated with their ability to trap free radicals. Ultrafiltered peptide fractions with low MW have a high potential to be used as natural alternatives to prevent lipid oxidation in foods.     

System-wide emissions implications of increased wind power penetration

This paper discusses the environmental effects of incorporating wind energy into the electric power system. We present a detailed emissions analysis based on comprehensive modeling of power system operations with unit commitment and economic dispatch for different wind penetration levels. First, by minimizing cost, the unit commitment model decides which thermal power plants will be utilized based on a wind power forecast, and then, the economic dispatch model dictates the level of production for each unit as a function of the realized wind power generation. Finally, knowing the power production from each power plant, the emissions are calculated. The emissions model incorporates the effects of both cycling and start-ups of thermal power plants in analyzing emissions from an electric power system with increasing levels of wind power. Our results for the power system in the state of Illinois show significant emissions effects from increased cycling and particularly start-ups of thermal power plants. However, we conclude that as the wind power penetration increases, pollutant emissions decrease overall due to the replacement of fossil fuels.