Molecules that target beta-amyloid

The devastating effects of Alzheimer's and related amyloidogenic diseases have inspired the synthesis and evaluation of numerous ligands to understand the molecular mechanism of the aggregation of the beta-amyloid peptide. Our review focuses on the current knowledge in this field with respect to molecules that have been demonstrated to interact with either oligomeric or fibrillar forms of the beta-amyloid peptide. We describe natural proteins, peptides, peptidomimetics, and small molecules that have been found to interfere with beta-amyloid aggregation. We also detail recent efforts in selecting molecules that target beta-amyloid isolated from antibody, protein, and peptide libraries. These new molecules will likely aid in deciphering the details of the aggregation pathway for the beta-amyloid peptide and provide reagents that may stabilize relevant oligomeric intermediates which likely have bearing on the pathophysiology of Alzheimer's disease. Moreover, the described anti-amyloid molecular toolbox will also provide an avenue for designing new diagnostic and therapeutic reagents.     

Ionic strength-induced formation of smectite quasicrystals enhances nitroaromatic compound sorption

Sorption of organic contaminants by soils is a determinant controlling their transport and fate in the environment. The influence of ionic strength on nitroaromatic compound sorption by K+- and Ca2+ -saturated smectite was examined. Sorption of 1,3-dinitrobenzene by K-smectite increased as KCl ionic strength increased from 0.01 to 0.30 M. In contrast, sorption by Ca-smectite at CaCl2 ionic strengths of 0.015 and 0.15 M remained essentially the same. The "salting-out" effect on the decrease of 1,3-dinitrobenzene aqueous solubility within this ionic strength range was <1.5% relative to the solubility in pure water. This decrease of solubility is insufficient to account for the observed increase of sorption by K-smectite with increasing KCl ionic strength. X-ray diffraction patterns and light absorbance of K-clay suspensions indicated the aggregation of clay particles and the formation of quasicrystal structures as KCI ionic strength increased. Sorption enhancement is attributed to the formation of better-ordered K-clay quasicrystals with reduced interlayer distances rather than to the salting-out effect. Dehydration of 1,3-dinitrobenzene is apparently a significant driving force for sorption, and we show for the first time that sorption of small, planar, neutral organic molecules, namely, 1,3-dinitrobenzene, causes previously expanded clay interlayers to dehydrate and collapse in aqueous suspension.     

Protective effect of dietary tomatine against dibenzo[a,l]pyrene (DBP)-induced liver and stomach tumors in rainbow trout

The potential anti-carcinogenic effects of tomatine, a mixture of commercial tomato glycoalkaloids alpha-tomatine and dehydrotomatine (10:1), were examined in the rainbow trout chemoprevention model. Prior to the chemoprevention study, a preliminary toxicity study revealed that tomatine in the diet fed daily at doses from 100 to 2000 parts per million (ppm) for 4 weeks was not toxic to trout. For the tumor study, replicate groups of 105 trout were fed diets containing dibenzo[a,l]pyrene (DBP) alone (224 ppm), (N = 3), DBP plus tomatine at 2000 ppm (N = 2), tomatine alone (N = 2), or control diet (N = 2) for 4 weeks. The fish were then returned to control diet for 8 months and necropsied for histopathology. Dietary tomatine was found to reduce DBP-initiated liver tumor incidence from 37.0 to 19.0% and stomach tumor incidence from 46.4 to 29.4%. Tomatine also reduced stomach tumor multiplicity. The tomatine-containing diets did not induce mortality, change in fish weights, or liver weights. No adverse pathological effects in the tissues of the fish on the tomatine diets were observed. Dose-response and chemopreventive mechanisms for tomatine protection remain to be examined. This is the first report on the anticarcinogenic effects of tomatine in vivo.     

Electrostimulation as a prosthesis for repair of information flow in a computer model of neocortex

Damage to a cortical area reduces not only information transmitted to other cortical areas, but also activation of these areas. This phenomenon, whereby the dynamics of a follower area are dramatically altered, is typically manifested as a marked reduction in activity. Ideally, neuroprosthetic stimulation would replace both information and activation. However, replacement of activation alone may be valuable as a means of restoring dynamics and information processing of other signals in this multiplexing system. We used neuroprosthetic stimulation in a computer model of the cortex to repair activation dynamics, using a simple repetitive stimulation to replace the more complex, naturalistic stimulation that had been removed. We found that we were able to restore activity in terms of neuronal firing rates. Additionally, we were able to restore information processing, measured as a restoration of causality between an experimentally recorded signal fed into the in silico brain and a cortical output. These results indicate that even simple neuroprosthetics that do not restore lost information may nonetheless be effective in improving the functionality of surrounding areas of cortex.     

Surveys of natural radiation exposure in UK dwellings with passive and active measurement techniques

A representative sample of over 2,000 UK dwellings was monitored for a year using thermoluminescent and etchable plastic dosemeters to measure gamma-ray dose rates and radon concentrations. The survey was carried out by post. Each householder completed a questionnaire on the type of dwelling and its characteristics. These data will be used in the assessment of the factors affecting indoor exposure. The mean gamma-ray dose rates were 0.062 and 0.057 μGy h^?1 in air and the mean radon concentrations were 25 and 18 Bq m^?3 for living areas and bedrooms respectively. Other results of the preliminary data analysis are given.More detailed surveys were conducted in areas where the local geology indicated that elevated exposures to natural radiation might occur. Over 800 dwellings were visited and measurements made of several parameters. The mean gamma-ray dose rates varied from 0.05 to 0.10 μGy h^?1 in air. The mean radon concentrations varied from 14 Bq m^?3 to 520 Bq m^?3. Other findings related to equilibrium factors and regional differences are discussed.     

DEVELOPMENT AND PRODUCTION OF FeAl BASED INTERMETALLIC ALLOYS

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Synthesis of 2-Nitroimino-5-Nitrohexahydro-1,3,5-Triazine via Chloride-Assisted Nitrolysis of a Tertiary Amine

An alternative synthesis of the insensitive energetic nitramine 2-nitroimino-5-nitrohexahydro-1,3,5-triazine ( 1 ) via nitrolysis of a tertiary amine is presented. Nitration of the tertiary amine precursor ( 2 ) is effected by chloride-assisted elimination of the tert-butyl moiety, with the chloramine presumably formed as an intermediate. The reaction fails to proceed in the absence of chloride at 0°C, however, its inclusion in the reaction system leads to a smooth conversion to ( 1 ) under mild nitrating conditions, which can be scaled up to yield multigram quantities. This is the first known example of a chloride-assisted nitrolysis of a tertiary amine to appear in the open literature.     

Sulfur specificity in the bench‐scale biological desulfurization of crude oil by Rhodococcus IGTS8

Biological removal of organic sulfur from petroleum feedstocks may offer an attractive alternative to conventional thermochemical treatment due to the mild operating conditions and greater reaction specificity afforded by the nature of biocatalysis. Previous investigations have either reported the desulfurization of model sulfur compounds in organic solvents or gross desulfurization of crude oil without data on which sulfur species were being removed. This study reports initial sulfur speciation data for thiophenic sulfur compounds present in crude oil which may be used as a guide both as to which species are treated by the biocatalyst investigated as well as to where biocatalyst development is needed to improve the extent of biological desulfurization when applied to whole crudes. Biodesulfurization of two different crude oils in the 22–31 ° API specific gravity range with total sulfur contents between 1 and 2% is demonstrated in 1‐dm³ batch stirred reactors using wild type Rhodococcus sp IGTS8. While analysis of the crudes before and after biodesulfurization did not reveal a decrease in total sulfur, GC–MS did reveal significant (43–99%) desulfurization of dibenzothiophenes (DBT) and substituted DBTs. Fractionation of the whole crude, followed by analysis using gas chromatography–sulfur chemiluminescence detection (GC–SCD) of the aromatic fraction of the Van Texas crude oil, demonstrated a reduction of sulfur in this fraction from 3.8% to 3.2%. This research indicates that IGTS8 may be capable of biodesulfurization of refined products such as gasoline and diesel whose predominant sulfur species are dibenzothiophenes. Further biocatalyst development would be needed for effective treatment of the spectrum of sulfur‐bearing compounds present in whole crudes.     

Products from rapid heating of a brown coal in the temperature range 400–2300 °C

The devolatilisation behaviour of Yallourn brown coal was investigated under rapid heating conditions using two different flash pyrolysers: a fluid-bed reactor giving coal particle heating rates of 10⁴ °Cs^?1 with a gas residence time of about 0.5 s and a shock tube which generated heating rates of the order of 10⁷ °Cs^?1 and a 1 ms reaction time. Yields of products are reported covering pyrolysis temperatures in the range 400–2300 °C. Hydrocarbon gas yields reached maximum values which were remarkably similar for both reactors although occurring at different temperatures. Carbon oxide production was also similar for both reactors with CO yields reaching 30% wt/wt daf coal. These high yields of CO are very different from those reported for slow heating conditions. It appears that on flash heating, coal decomposition pathways change in a manner which increases CO yields at the expense of H₂0 and to a lesser extent C0₂, resulting in the volatilisation of additional carbon from the coal.