Virtual Affinity Fingerprints for Target Fishing: A New Application of Drug Profile Matching

We recently introduced Drug Profile Matching (DPM), a novel virtual affinity fingerprinting bioactivity prediction method. DPM is based on the docking profiles of ca. 1200 FDA-approved small-molecule drugs against a set of nontarget proteins and creates bioactivity predictions based on this pattern. The effectiveness of this approach was previously demonstrated for therapeutic effect prediction of drug molecules. In the current work, we investigated the applicability of DPM for target fishing, i.e. for the prediction of biological targets for compounds. Predictions were made for 77 targets, and their accuracy was measured by Receiver Operating Characteristic (ROC) analysis. Robustness was tested by a rigorous 10-fold cross-validation procedure. This procedure identified targets (N = 45) with high reliability based on DPM performance. These 45 categories were used in a subsequent study which aimed at predicting the off-target profiles of currently approved FDA drugs. In this data set, 79% of the known drug-target interactions were correctly predicted by DPM, and additionally 1074 new drug-target interactions were suggested. We focused our further investigation on the suggested interactions of antipsychotic molecules and confirmed several interactions by a review of the literature

A water-soluble core material for manufacturing hollow composite sections

This paper presents the development of a low-cost water-soluble core material, which is suitable for producing hollow composite structures via high pressure moulding processes, such as compression moulding and resin transfer moulding. The bulk material of the core is sodium chloride (NaCl), which is held together by a watersoluble trehalose binder. The composition of the core has been optimised to provide acceptable dissolution rates and mechanical properties for high volume structural composite applications. The compressive strength of the NaCl core was 57 MPa at ambient temperature, which reduced to 20 MPa when tested at 120 °C. The compressive strength at elevated temperature was approximately 4 times higher than for a water-soluble commercial benchmark and 33 times higher than a conventional structural closed-cell foam. The specific dissolution rate of the NaCl core was between 0.14 and 1.23 kg/(min·m2), depending on processing parameters and the coefficient of thermal expansion was approximately 43 × 10−6/K. A practical example has been presented to demonstrate how the removable core can be used to produce a representative hollow section of an integrally stiffened panel

Malaria prophylaxis policy for travellers from Europe to the Indian Sub Continent

Analysis of malaria imported into eight European countries from the Indian sub-continent (ISC) (India, Pakistan, Bangladesh and Sri Lanka) led to a consensus statement on the use of chemoprophylaxis within TropNetEurop. The proportion of cases from the ISC in 2004 ranged from 1.4%–4.6% of total imported cases. Plasmodium falciparum cases reported from the eight countries was only 23 (13% of all cases from the region). Total malaria reports between 1999–2004 fell from 317 to 180. The risk of malaria in UK residents visiting the region was > 1 case per 1,000 years exposed. The group recommended non-selective prescribing of chemoprophylaxis for visitors to India, Pakistan, Bangladesh and Sri Lanka should be dropped

Effects of doping and epitaxy on optical behavior of NaNbO3 films

Cube-on-cube epitaxy of perovskite sub-cell of Pr-doped and undoped NaNbO3 is obtained in 130-nm-thick films on top of (La0.18Sr0.82)(Al0.59Ta0.41)O3 (001) substrates. Experimental studies show that the edge of optical absorption red-shifts and some interband transitions change in the films compared to crystals. Bright red luminescence is achieved at room-temperature under ultraviolet excitation in the Pr-doped film. An interband mechanism of luminescence excitation is detected in the film, which is in contrast to the intervalence charge transfer mechanism in the crystal. The results are discussed in terms of epitaxially induced changes of crystal symmetry and ferroelectric polarization in the films. It is suggested that the band structure and interband transitions in NaNbO3and the transition probabilities in the Pr ions can be significantly modified by these changes.Peer reviewe

Pressure balance at the magnetopause: Experimental studies

The pressure balance at the magnetopause is formed by magnetic field and plasma in the magnetosheath, on one side, and inside the magnetosphere, on the other side. In the approach of dipole earth's magnetic field configuration and gas-dynamics solar wind flowing around the magnetosphere, the pressure balance predicts that the magnetopause distance R depends on solar wind dynamic pressure Pd as a power low R ~ Pd^alpha, where the exponent alpha=-1/6. In the real magnetosphere the magnetic filed is contributed by additional sources: Chapman-Ferraro current system, field-aligned currents, tail current, and storm-time ring current. Net contribution of those sources depends on particular magnetospheric region and varies with solar wind conditions and geomagnetic activity. As a result, the parameters of pressure balance, including power index alpha, depend on both the local position at the magnetopause and geomagnetic activity. In addition, the pressure balance can be affected by a non-linear transfer of the solar wind energy to the magnetosheath, especially for quasi-radial regime of the subsolar bow shock formation proper for the interplanetary magnetic field vector aligned with the solar wind plasma flow.Comment: 8 pages, 2 figure

Transition from Fireball to Poynting-flux-dominated Outflow in Three-Episode GRB 160625B

The ejecta composition is an open question in gamma-ray bursts (GRB) physics. Some GRBs possess a quasi-thermal spectral component in the time-resolved spectral analysis, suggesting a hot fireball origin. Others show a featureless non-thermal spectrum known as the "Band" function, consistent with a synchrotron radiation origin and suggesting that the jet is Poynting-flux-dominated at the central engine and likely in the emission region as well. There are also bursts showing a sub-dominant thermal component and a dominant synchrotron component suggesting a likely hybrid jet composition. Here we report an extraordinarily bright GRB 160625B, simultaneously observed in gamma-rays and optical wavelengths, whose prompt emission consists of three isolated episodes separated by long quiescent intervals, with the durations of each "sub-burst" being $\sim$ 0.8 s, 35 s, and 212 s, respectively. Its high brightness (with isotropic peak luminosity L$_{\rm p, iso}\sim 4\times 10^{53}$ erg/s) allows us to conduct detailed time-resolved spectral analysis in each episode, from precursor to main burst and to extended emission. The spectral properties of the first two sub-bursts are distinctly different, allowing us to observe the transition from thermal to non-thermal radiation between well-separated emission episodes within a single GRB. Such a transition is a clear indication of the change of jet composition from a fireball to a Poynting-flux-dominated jet.Comment: Revised version reflecting the referees' comments. 27 pages, 11 figures, 5 tables. The final edited version will appear in Nature Astronom