Enhanced downregulation of the p75 nerve growth factor receptor by cholesteryl and bis-cholesteryl antisense oligonucleotides

The effects of conjugating cholesterol to either or both ends of a phosphorothioate (PS) oligonucleotide were analyzed in terms of cellular uptake and antisense efficacy. The oligo sequence was directed against the p75 nerve growth factor receptor (p75), and was tested in differentiated PC12 cells, which express high levels of this protein. The addition of a single cholesteryl group to the 5'-end significantly increased cellular uptake and improved p75 mRNA downregulation compared with the unmodified PS oligo, However, only a minor degree of downregulation of p75 protein was obtained with 5' cholesteryl oligos, Three different linkers was used to attach the 5' cholesteryl group but were found not to have any impact on efficacy. Addition of a single cholesteryl group to the 3'-end led to greater p75 mRNA downregulation (31%) and p75 protein downregulation (28%) than occurred with the 5' cholesteryl oligos. The biggest improvement in antisense efficacy, both at the mRNA and protein levels, was obtained from the conjugation of cholesterol to both ends of the oligo. One of the bis-cholesteryl oligos was nearly as effective as cycloheximide at decreasing synthesis of p75, The bis-cholesteryl oligos also displayed significant efficacy at 1 mu M, whereas the other oligos required 5 mu M to be effective. The enhanced efficacy of bis-cholesteryl oligos is likely to be due to a combination of enhanced cellular uptake and resistance to both 5' and 3' exonucleases.

Copper/MCM-41 as catalyst for photochemically enhanced oxidation of phenol by hydrogen peroxide

Heterogeneous copper catalyst was developed using the mesoporous molecular sieve MCM-41 as the catalyst support. Copper was impregnated onto the support. Catalysts with different copper loadings were obtained. The performance of the developed catalysts was evaluated in photochemically enhanced oxidation of phenol using hydrogen peroxide as the oxidant. The catalyst was found to significantly increase the oxidation rate and enhance the removal level of phenol with UV light present. The effects of copper loading on the catalyst, photo (UV), H2O2 concentration, and catalyst dosage on the photo-oxidation of phenol were studied. (C) 2001 Elsevier Science B.V. All rights reserved.

Spatial data mining for enhanced soil map modelling

The principle of using induction rules based on spatial environmental data to model a soil map has previously been demonstrated Whilst the general pattern of classes of large spatial extent and those with close association with geology were delineated small classes and the detailed spatial pattern of the map were less well rendered Here we examine several strategies to improve the quality of the soil map models generated by rule induction Terrain attributes that are better suited to landscape description at a resolution of 250 m are introduced as predictors of soil type A map sampling strategy is developed Classification error is reduced by using boosting rather than cross validation to improve the model Further the benefit of incorporating the local spatial context for each environmental variable into the rule induction is examined The best model was achieved by sampling in proportion to the spatial extent of the mapped classes boosting the decision trees and using spatial contextual information extracted from the environmental variables.

Can I have your attention please: Repressors and enhanced P3 to emotional stimuli

In four experiments ERPs to emotional (negative and positive) and neutral stimuli were examined as a function of participants’ trait anxiety and repressivedefensiveness. The experiments investigated the time course of attentional bias in the processing of such stimuli. Pictures of angry, happy, and neutral faces were used in two of the experiments and pictures ofmutilated, happy, and neutral faces were used in the others. ERP’s to emotional and neutral stimuli were recorded from parietal, temporal, and frontal sites. Analysis of the P3 component indicated that the peak magnitude of the P3 at the parietal and temporal sites reflected an interactive function of trait anxiety and defensiveness. Repressors (low reported anxiety, high defensiveness) showed a consistent pattern of greater P3 magnitude at the parietal and temporal sites for emotional faces (angry, happy, and mutilated) than did high-anxious and low-anxious participants. Participants did not differ in P3 magnitude when ERPs to neutral stimuli were investigated (e.g., a fixation cross). The findings indicate that Repressors dedicate greater processing resources to emotional material, as compared to neutral material, than either the high-anxious or low-anxious individuals. Results of the four experiments are discussed within the theoretical framework of Derakshan and Eysenck (1998). The importance of understanding the role of differences in information processing, in the experience and avoidance of emotional information, as a function of trait anxiety and defensiveness is emphasized.

The Arabidopsis mutant iop1 exhibits induced over-expression of the plant defensin gene PDF1.2 and enhanced pathogen resistance

Jasmonate and ethylene are concomitantly involved in the induction of the Arabidopsis plant defensin gene PDF1.2. To define genes in the signal transduction pathway leading to the induction of PDF1.2, we screened for-mutants with induced over-expression of a beta-glucuronidase reporter, under the control of the PDF1.2 promoter. One mutant, iop1 (induced over-expressor of PDF1.2) produced small plants that showed induced over-expression of the pathogenesis-related genes PR-3, PR-4 and PR-1,2 (PDF1.2), combined with a down-regulated induction of PR-1 upon pathogen inoculation. The iop1 mutant showed enhanced resistance to a number of necrotrophic pathogens.

Rare Earth Doped SnO(2) Nanoscaled Powders and Coatings: Enhanced Photoluminescence in Water and Waveguiding Properties

Luminescent Eu(3+) and Er(3+) doped SnO(2) powders have been prepared by Sn(4+) hydrolysis followed by a controlled growth reaction using a particle`s surface modifier in order to avoid particles aggregation. The powders so obtained doped with up to 2 mol% rare earth ions are fully redispersable in water at pH > 8 and present the cassiterite structure. Particles size range from 3 to 10 nm as determined by Photon Correlation Spectroscopy. Rare earth ions were found to be essentially incorporated into the cassiterite structure, substituting for Sn(4+), for doping concentration smaller than 0.05 mol%. For higher concentration they are also located at the particles surface. The presence of Eu(3+) ions at the surface of the particles hinder their growth and has therefore allowed the preparation of new materials consisting of water redispersable powders coated with Eu(3+)-beta dike-tonate complexes. Enhanced UV excited photoluminescence was observed in water. SnO(2) single layers with thickness up to 200 nm and multilayer coatings were spin coated on borosilicate glass substrates from the colloidal suspensions. Waveguiding properties were evaluated by the prism coupling technique. For a 0.3 mu m planar waveguide single propagating mode was observed with attenuation coefficient of 3.5 dB/cm at 632.8 nm.

Association between dopamine transporter (DATI) genotype, left-sided inattention, and an enhanced response to methylphenidate in attention-deficit hyperactivity disorder

A polymorphism of the dopamine transporter gene (DAT1, 10-repeat) is associated with attention-deficit hyperactivity disorder (ADHD) and has been linked to an enhanced response to methylphenidate (MPH). One aspect of the attention deficit in ADHD includes a subtle inattention to left space, resembling that seen after right cerebral hemisphere damage. Since left-sided inattention in ADHD may resolve when treated with MPH, we asked whether left-sided inattention in ADHD was related to DAT1 genotype and the therapeutic efficacy of MPH. A total of 43 ADHD children and their parents were genotyped for the DAT1 30 variable number of tandem repeats polymorphism. The children performed the Landmark Test, a well-validated measure yielding a spatial attentional asymmetry index ( leftward to rightward attentional bias). Parents rated their child's response to MPH retrospectively using a three-point scale ( no, mediocre or very good response). Additionally, parents used a symptom checklist to rate behavior while on and off medication. A within-family control design determined whether asymmetry indices predicted biased transmission of 10-repeat parental DAT1 alleles and/or response to MPH. It was found that left-sided inattention predicted transmission of the 10-repeat allele from parents to probands and was associated with the severity of ADHD symptomatology. Children rated as achieving a very good response to MPH displayed left-sided inattention, while those rated as achieving a poorer response did not. Our results suggest a subgroup of children with ADHD for whom the 10-repeat DAT1 allele is associated with left-sided inattention. MPH may be most efficacious in this group because it ameliorates a DAT1-mediated hypodopaminergic state.

Privacy and security enhanced offline oblivious transfer for massive data distribution

Unauthorized accesses to digital contents are serious threats to international security and informatics. We propose an offline oblivious data distribution framework that preserves the sender's security and the receiver's privacy using tamper-proof smart cards. This framework provides persistent content protections from digital piracy and promises private content consumption.

Disruption of NaS1 sulfate transport function in mice leads to enhanced acetaminophen-induced hepatotoxicity

Sulfate is required for detoxification of xenobiotics such as acetaminophen (APAP), a leading cause of liver failure in humans. The NaS1 sulfate transporter maintains blood sulfate levels sufficiently high for sulforiation reactions to work effectively for drug detoxification. In the present study, we identified two loss-of-function polymorphisms in the human NaS1 gene and showed the Nas1-null mouse to be hypersensitive to APAP hepatotoxicity. APAP treatment led to increased liver damage and decreased hepatic glutathione levels in the hyposulfatemic Nas1-null mice compared with that in normosulfatemic wild-type mice. Analysis of urinary APAP metabolites revealed a significantly lower ratio of APAP-sulfate to APAP-glucuronide in the Nas1-null mice. These results suggest hyposulfatemia increases sensitivity to APAP-induced hepatotoxicity by decreasing the sulfonation capacity to metabolize APAP. In conclusion, the results of this study highlight the importance of plasma sulfate level as a key modulator of acetaminophen metabolism and suggest that individuals with reduced NaS1 sulfate transporter function would be more sensitive to hepatotoxic agents.

Periodic electric field enhanced transport through membranes

We examine the mean flux across a homogeneous membrane of a charged tracer subject to an alternating, symmetric voltage waveform. The analysis is based on the Nernst-Planck flux equation, with electric field subject to time dependence only. For low frequency electric fields the quasi steady-state flux can be approximated using the Goldman model, which has exact analytical solutions for tracer concentration and flux. No such closed form solutions can be found for arbitrary frequencies, however we find approximations for high frequency. An approximation formula for the average flux at all frequencies is also obtained from the two limiting approximations. Numerical integration of the governing equation is accomplished by use of the numerical method of lines and is performed for four different voltage waveforms. For the different voltage profiles, comparisons are made with the approximate analytical solutions which demonstrates their applicability. (c) 2005 Elsevier B.V. All rights reserved.

Supersonic velocimetry in a shock tube using laser enhanced ionisation and planar laser induced fluorescence

A novel flow-tagging technique is presented which was employed to measure gas velocities in the free stream of a shock tube. This method is based on the laser spectroscopic techniques of Laser-Enhanced Ionisation (LEI) and Laser-Induced Fluorescence (LIF). The flow in the shock tube is seeded with small amounts of sodium, and LEI is used to produce a substantial depletion of neutral sodium atom concentration in a well-defined region of the flow, by using two wavelength-resonance excitation and subsequent collisional ionisation. At a specific time delay, single-laser-pulse planar LIF is utilised to produce a two-dimensional (2-D) inverse image of the depleted tagged region downstream of the flow. By measuring the displacement of the tagged region, free stream velocities in a shock tube were determined. Large variations in the concentration of sodium seeded into the flow were observed and even in the presence of these large variations accurate free-stream velocity measurements were obtained. The experimentally determined value for velocity compares very well with the predicted velocity.

Measurements of neutral atom diffusion and electron-ion recombination by laser enhanced ionisation and planar laser induced fluorescence in an air-acetylene flame

The spatial and temporal evolution of a depleted atomic distribution created by laser enhanced ionisation (LEI) was employed to determine both a diffusion coefficient for sodium (Na) and an electron (e(-)) and sodium ion recombination rate coefficient in an analytical air-C2H2 flame. A depleted distribution of neutral sodium atoms was produced in a flame by ionising approximately 80% of the irradiated sodium atoms in a well defined region using a two step LEI excitation scheme. Following depletion by ionisation, planar laser induced fluorescence (PLIF) images of the depleted region recorded the diffusion and decay of the depleted Na distribution for different depletion-probe delays. From measurements of the diffused width of the distribution, an accurate diffusion coefficient D = (1.19 +/- 0.03) x 10(-3) m(2) s(-1) for Na was determined in teh burnt gases of the flame. Measurements of the integrated fluorescence intensity in the depleted region for different depletion-probe delays were related to an increase in atomic sodium concentration caused by electron-ion recombination. At high concentrations (greater than or equal to 50 mu g ml(-1)), where the electron and ion concentrations in the depleted region were assumed equal, a recombination rate coefficient of 4.2 x 10(-9) cm(3) s(-1) was calculated. (C) 1997 Elsevier Science B.V.

Contrast-enhanced magnetic resonance imaging identifies focal regions of intramyocardial fibrosis, in patients with severe aortic valve disease: Correlation with quantitative histopathology

Background Chronic aortic valve disease (AVD) is characterized by progressive accumulation of interstitial myocardial fibrosis (MF). However, assessment of MF accumulation has only been possible through histologic analyses of endomyocardial biopsies. We sought to evaluate contrast-enhanced magnetic resonance imaging (ce-MRI) as a noninvasive method to identify the presence of increased MF in patients with severe AVD. Methods Seventy patients scheduled to undergo aortic valve replacement surgery were examined by cine and ce-MRI in a 1.5-T scanner. Cine images were used for the assessment of left ventricular (LV) volumes, mass, and function. Delayed-enhancement images were used to characterize the regions of MF. In addition, histologic analyses of myocardial samples obtained during aortic valve replacement surgery were used for direct quantification of interstitial MF. Ten additional subjects who died of noncardiac causes served as controls for the quantitative histologic analyses. Results Interstitial MF determined by histopathologic analysis was higher in patients with AVID than in controls (2.7% +/- 2.0% vs 0.6% +/- 0.2%, P =.001). When compared with histopathologic results, ce-MRI demonstrated a sensitivity of 74%, a specificity of 81%, and an accuracy of 76% to identify AVD patients with increased interstitial MF There was a significant inverse correlation between interstitial MF and LV ejection fraction (r = -0.67, P <.0001). Accordingly, patients with identifiable focal regions of MF by ce-MRI exhibited worse LV systolic function than those without MF (45% +/- 14% vs 65% +/- 14%, P <.0001). Conclusions Contrast-enhanced MRI allows for the noninvasive detection of focal regions of MF in patients with severe AVD. Moreover, patients with identifiable MF by ce-MRI exhibited worse LV functional parameters. (Am Heart J 2009; 157:361-8.)