| 1. |
- Acciari, V. A., et al.
(author)
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Radio Imaging of the Very-High-Energy gamma-Ray Emission Region in the Central Engine of a Radio Galaxy
- 2009
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 325:5939, s. 444-448
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Journal article (peer-reviewed)abstract
- The accretion of matter onto a massive black hole is believed to feed the relativistic plasma jets found in many active galactic nuclei (AGN). Although some AGN accelerate particles to energies exceeding 10(12) electron volts and are bright sources of very-high-energy (VHE) gamma-ray emission, it is not yet known where the VHE emission originates. Here we report on radio and VHE observations of the radio galaxy Messier 87, revealing a period of extremely strong VHE gamma-ray flares accompanied by a strong increase of the radio flux from its nucleus. These results imply that charged particles are accelerated to very high energies in the immediate vicinity of the black hole.
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| 2. |
- Raiteri, C. M., et al.
(author)
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WEBT and XMM-Newton observations of 3C 454.3 during the post-outburst phase - Detection of the little and big blue bumps
- 2007
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 473:3, s. 819-827
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Journal article (peer-reviewed)abstract
- Context. The quasar-type blazar 3C 454.3 was observed to undergo an unprecedented optical outburst in spring 2005, affecting the source brightness from the near-IR to the X-ray frequencies. This was first followed by a millimetric and then by a radio outburst, which peaked in February 2006. Aims. In this paper we report on follow-up observations to study the multiwavelength emission in the post-outburst phase. Methods. Radio, near-infrared, and optical monitoring was performed by the Whole Earth Blazar Telescope (WEBT) collaboration in the 2006-2007 observing season. XMM-Newton observations on July 2-3 and December 18-19, 2006 added information on the X-ray and UV states of the source. Results. The source was in a faint state. The radio flux at the higher frequencies showed a fast decreasing trend, which represents the tail of the big radio outburst. It was followed by a quiescent state, common at all radio frequencies. In contrast, moderate activity characterized the near-IR and optical light curves, with a progressive increase of the variability amplitude with increasing wavelength. We ascribe this redder-when-brighter behaviour to the presence of a ""little blue bump"" due to line emission from the broad line region, which is clearly visible in the source spectral energy distribution (SED) during faint states. Moreover, the data from the XMM- Newton Optical Monitor reveal a rise of the SED in the ultraviolet, suggesting the existence of a "" big blue bump"" due to thermal emission from the accretion disc. The X-ray spectra are well fitted with a power- law model with photoelectric absorption, possibly larger than the Galactic one. However, the comparison with previous X-ray observations would imply that the amount of absorbing matter is variable. Alternatively, the intrinsic X-ray spectrum presents a curvature, which may depend on the X-ray brightness. In this case, two scenarios are possible. i) There is no extra absorption, and the X-ray spectrum hardens at low energies, the hardening being more evident in bright states; ii) there is a constant amount of extra absorption, likely in the quasar environment, and the X-ray spectrum softens at low energies, at least in faint X-ray states. This softening might be the result of a flux contribution by the high-frequency tail of the big blue bump.
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| 3. |
- Lindfors, L, et al.
(author)
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Amorphous drug nanosuspensions. 1. Inhibition of Ostwald ripening
- 2006
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In: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 22:3, s. 906-910
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Journal article (peer-reviewed)abstract
- Amorphous drug nanosuspensions are prone to particle growth due to Ostwald ripening. By incorporating a second component of extremely low aqueous solubility, Ostwald ripening can be inhibited. These studies indicate that to inhibit ripening, the drug/inhibitor mixture (in the particles) must form a single phase. The drug/inhibitor mixture can be characterized by the interaction parameter chi using the Bragg-Williams theory, in which single phase mixtures are obtained for chi < 2. The chi parameter can be calculated from the (crystalline) solubility of the drug in the inhibitor, provided the inhibitor is a liquid, and the melting entropy and temperature of the drug.
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| 4. |
- Lindfors, L, et al.
(author)
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Amorphous drug nanosuspensions. 2. Experimental determination of bulk monomer concentrations
- 2006
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In: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 22:3, s. 911-916
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Journal article (peer-reviewed)abstract
- A simple turbidimetric method was developed to measure the bulk concentration of drug in nanosuspensions. The bulk concentrations measured were in the range from 1 mu M to 1 mM. The accuracy of the method was checked by determination of the bulk concentration of crystalline nanosuspensions, i.e., the crystalline solubility, which compared favorably to solubilities measured by a conventional method. Results obtained for amorphous nanosuspensions agreed with predictions using a theory describing the relative solubility between a supercooled liquid and a crystal. Further, it was found that the bulk concentration in Ostwald ripening inhibited amorphous nanosuspensions and could be lowered by incorporation of higher amounts of the inhibitor, in agreement with predictions using the Bragg-Williams theory of nonideal solutions.
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| 5. |
- Lüder, Kai, 1963, et al.
(author)
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In silico prediction of drug solubility: 2. Free energy of solvation in pure melts
- 2007
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In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 111:7, s. 1883-1892
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Journal article (peer-reviewed)abstract
- The solubility of drugs in water is investigated in a series of papers and in the current work. The free energy of solvation, Delta G(vl)(center dot), of a drug molecule in its pure drug melt at 673.15 K (400 degrees C) has been obtained for 46 drug molecules using the free energy perturbation method. The simulations were performed in two steps where first the Coulomb and then the Lennard-Jones interactions were scaled down from full to no interaction. The results have been interpreted using a theory assuming that Delta G(vl)(center dot) = Delta G(cav) + E-LJ + E-C/2 where the free energy of cavity formation, Delta G(cav), in these pure drug systems was obtained using hard body theories, and E-LJ and E-C are the Lennard-Jones and Coulomb interaction energies, respectively, of one molecule with the other ones. Since the main parameter in hard body theories is the volume fraction, an equation of state approach was used to estimate the molecular volume. Promising results were obtained using a theory for hard oblates, in which the oblate axial ratio was calculated from the molecular surface area and volume obtained from simulations. The Coulomb term, E-C/2, is half of the Coulomb energy in accord with linear response, which showed good agreement with our simulation results. In comparison with our previous results on free energy of hydration, the Coulomb interactions in pure drug systems are weaker, and the van der Waals interactions play a more important role.
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| 6. |
- Lüder, Kai, 1963, et al.
(author)
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In silico prediction of drug solubility. 3. Free energy of solvation in pure amorphous matter
- 2007
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In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 111:25, s. 7303-7311
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Journal article (peer-reviewed)abstract
- The solubility of drugs in water is investigated in a series of papers. In this work, we address the process of bringing a drug molecule from the vapor into a pure drug amorphous phase. This step enables us to actually calculate the solubility of amorphous drugs in water. In our general approach, we, on one hand, perform rigorous free energy simulations using a combination of the free energy perturbation and thermodynamic integration methods. On the other hand, we develop an approximate theory containing parameters that are easily accessible from conventional Monte Carlo simulations, thereby reducing the computation time significantly. In the theory for solvation, we assume that Delta G(center dot) = Delta G(cav) + E-LJ + E-C/2, where the free energy of cavity formation, Delta G(cav), in pure drug systems is obtained using a theory for hard-oblate spheroids, and E-LJ and E-C are the Lennard-Jones and Coulomb interaction energies between the chosen molecule and the others in the fluid. The theoretical predictions for the free energy of solvation in pure amorphous matter are in good agreement with free energy simulation data for 46 different drug molecules. These results together with our previous studies support our theoretical approach. By using our previous data for the free energy of hydration, we compute the total free energy change of bringing a molecule from the amorphous phase into water. We obtain good agreement between the theory and simulations. It should be noted that to obtain accurate results for the total process, high precision data are needed for the individual subprocesses. Finally, for eight different substances, we compare the experimental amorphous and crystalline solubility in water with the results obtained by the proposed theory with reasonable success.
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| 7. |
- Mallbris, L., et al.
(author)
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The establishment and utility of Sweha-Reg : A Swedish population-based registry to understand hereditary angioedema
- 2007
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In: BMC Dermatology. - : Springer Science and Business Media LLC. - 1471-5945. ; 7
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Journal article (peer-reviewed)abstract
- Background: The importance of acquiring comprehensive epidemiological and clinical data on hereditary angioedema has increasingly caught the attention of physicians and scientists around the world. The development of networks and creation of comprehensive policies to improve care of people suffering from rare diseases, such as hereditary angioedema, is a stated top priority of the European Union. Hereditary angioedema is a rare disease, that it may be life-threatening. Although the exact prevalence is unknown, current estimates suggest that it is 1/10,000-1/150,000 individuals. The low prevalence requires combined efforts to gain accurate epidemiological data on the disease and so give us tools to reduce morbidity and mortality, and improve quality of life of sufferers. Methods: Sweha-Reg is a population-based registry of hereditary angioedema in Sweden with the objectives of providing epidemiological data, and so creates a framework for the study of this disease. The registry contains individual-based data on diagnoses, treatments and outcomes. Conclusion: The present manuscript seeks to raise awareness of the existence of Sweha-Reg to stimulate the international collaboration of registries. A synthesis of data from similar registries across several countries is required to approach an inclusive course understanding of HAE. © 2007 Mallbris et al, licensee BioMed Central Ltd.
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| 8. |
- Westergren, J., et al.
(author)
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In silico prediction of drug solubility: 1. Free energy of hydration
- 2007
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In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 111:7, s. 1872-1882
-
Journal article (peer-reviewed)abstract
- As a first step in the computational prediction of drug solubility the free energy of hydration, Delta G(vw)(center dot), in TIP4P water has been computed for a data set of 48 drug molecules using the free energy of perturbation method and the optimized potential for liquid simulations all-atom force field. The simulations were performed in two steps, where first the Coulomb and then the Lennard-Jones interactions between the solute and the water molecules were scaled down from full to zero strength to provide physical understanding and simpler predictive models. The results have been interpreted using a theory assuming Delta G(vw)(center dot) = A(MS)gamma + E-LJ + E-C/2 where A(MS) is the molecular surface area, gamma is the water-vapor surface tension, and E-LJ and E-C are the solute-water Lennard-Jones and Coulomb interaction energies, respectively. It was found that by a proper definition of the molecular surface area our results as well as several results from the literature were found to be in quantitative agreement using the macroscopic surface tension of TIP4P water. This is in contrast to the surface tension for water around a spherical cavity that previously has been shown to be dependent on the size of the cavity up to a radius of similar to 1 nm. The step of scaling down the electrostatic interaction can be represented by linear response theory.
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