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11.
  • Bouchene, Salim, 1984-, et al. (creator_code:aut_t)
  • Application of a whole-body physiologically based pharmacokinetic model to describe the plasma and urine disposition of colistin and colistin methanesulfonate (CMS) in healthy volunteers
  • swepub:Mat_publicationother_t (swepub:level_scientificother_t)abstract
    • Objectives: The primary aim of this work was to develop a whole-body physiologically based pharmacokinetic (WBPBPK) model to describe CMS and colistin disposition in human plasma and urine. The secondary aim of this analysis was to use the WBPBPK model to predict CMS and colistin tissue distribution in typical individuals with different pathophysiological changes and receiving different dosing regimens.Methods: Twelve healthy males were included in the analysis. They received a single dose of 80 mg CMS (1 million unit) through a 1-h intravenous infusion. Venous blood was collected between 0 and 18 h post dose. Fractionated urine samples were collected between 0 and 24 h after dose. A WBPBPK model initially developed in rat was further detailed with the addition of a specific urinary tract (UT) model. The Kp values of CMS and colistin were estimated for all tissues using experimental Kp prior values from rat tissue homogenates.Results: The model adequately described CMS and colistin concentrations over time in plasma and in urine. A shared first order elimination rate constant was estimated to depict the hydrolysis of CMS in plasma and tissues. A separate hydrolysis rate constant for CMS was estimated in urine, and was lower than in plasma and tissues. A shared non-renal elimination rate constant of colistin was estimated in plasma and in tissues. CMS and colistin disposition in urine was well characterized by the UT model. The tubular reabsorption of colistin was best described by a saturable model estimating the colistin affinity constant, KM. Non-specific binding of colistin in the UT lumen was accounted for using a linear relationship.Conclusion: The WBPBPK developed in this study characterized plasma and urine PK of CMS and colistin in human well. This model was used as a new framework to predict colistin exposure in the tissues of interest under different physiological conditions. The model can be easily refined when new data are available and can be combined to PKPD models to increase the understanding of the concentration-effect relationship at target sites.
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12.
  • Bouchene, Salim, et al. (creator_code:aut_t)
  • Development of a Whole-Body Physiologically Based Pharmacokinetic Model for Colistin and Colistin methanesulfonate (CMS) in Rat
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • Colistin is a polymyxin antibiotic which is used to treat patients infected with multidrug resistant Gram negative bacteria (MDR-GNB). The objective of this work was to develop a whole-body physiologically based pharmacokinetic (WBPBPK) model in rat for colistin and its prodrug, CMS. The Kp prior values of colisin and CMS used in the WBPBPK model were either measured ex vivo in rat tissue homogenates or calculated using an in silico model. The PK parameters were estimated fitting plasma concentrations from rats receiving an i.v. bolus of CMS. In the WBPBPK model, the tissue distribution was assumed to be well-stirred and perfusion-limited. Three scenarios were investigated: estimating the Kp values using in silico Kp prior values (I), estimating the Kp values using the Kp prior values from ex vivo experiments (II) and fixing the Kp values to the experimental ex vivo Kp values (III). The WBPBPK model well described CMS and colistin plasma concentration-time profiles. Colistin Kp values in kidneys were higher than in the other tissues. The predicted concentrations in tissue were highest for kidneys and brain which might be due to a high affinity for these tissues and/or active transport processes that remain poorly elucidated. The clearance estimates of CMS and colistin were in agreement with previously reported values in the literature. The model developed in this study might be a valuable tool in drug development to understand the disposition of colistin or new polymyxin candidates as well as to guide for optimal dosing regimens.
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13.
  • Bouchene, Salim, 1984-, et al. (creator_code:aut_t)
  • Development of an interspecies whole-body physiologically based pharmacokinetic (WBPBPK) model for colistin methanesulfonate (CMS) and colistin in five animal species and evaluation of its predictive ability in human
  • swepub:Mat_publicationother_t (swepub:level_scientificother_t)abstract
    • Background and purposeColistin is a last-line antibiotic administered as the prodrug colistin methanesulfonate (CMS) for the treatment of multidrug resistant Gram-negative bacterial infections. Whole-body physiologically based pharmacokinetic (WBPBPK) models are valuable tools to understand and characterize drug disposition, predict tissue distribution and interpret exposure-response relationship. The aim of this work was to develop a WBPBPK model for colistin and CMS in five animal species and evaluate the utility of the model for predicting colistin and CMS disposition in human.MethodsA nonlinear mixed-effects WBPBPK model previously developed in rats was extended to describe CMS and colistin plasma data of animals from 5 different species (40 mice, 6 rats, 3 rabbits, 3 baboons and 2 pigs) that had received single doses of CMS. CMS renal clearance and hydrolysis to colistin were allometrically scaled based on glomerular filtration rate (GFR) and tissue volumes, respectively. For the non-renal colistin clearance, three scaling models were evaluated: volume based allometric scaling, volume and maximum lifespan potential (MLP) based allometric scaling, and estimation of specie-specific parameters. Tissue concentrations were predicted for all species. The WBPBPK model was then used to predict human plasma concentrations, which were compared to observed human plasma PK data extracted from literature.ResultsThe description of the plasma PK of CMS and colistin in mice, rats, rabbits, baboons and pigs was satisfactory. The volume and MLP based allometric scaling of the non-renal clearance of colistin was best at characterizing colistin concentration-time course, even if a misprediction remained in pigs. In human however, allometric scaling without MLP was closest to the observed data, with satisfactory prediction of the CMS plasma profiles and a slight overprediction of colistin plasma PK profiles.ConclusionsInterspecies WBPBPK models were developed to describe the disposition of CMS and colistin across five animal species and human plasma concentrations of CMS and colistin were predicted in the right ranges.
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14.
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15.
  • Ching, Tao-Chung, et al. (creator_code:aut_t)
  • The JCMT BISTRO-2 Survey: Magnetic Fields of the Massive DR21 Filament
  • 2022
  • record:In_t: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 941:2
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • We present 850 mu m dust polarization observations of the massive DR21 filament from the B-fields In STar-forming Region Observations (BISTRO) survey, using the POL-2 polarimeter and the SCUBA-2 camera on the James Clerk Maxwell Telescope. We detect ordered magnetic fields perpendicular to the parsec-scale ridge of the DR21 main filament. In the subfilaments, the magnetic fields are mainly parallel to the filamentary structures and smoothly connect to the magnetic fields of the main filament. We compare the POL-2 and Planck dust polarization observations to study the magnetic field structures of the DR21 filament on 0.1-10 pc scales. The magnetic fields revealed in the Planck data are well-aligned with those of the POL-2 data, indicating a smooth variation of magnetic fields from large to small scales. The plane-of-sky magnetic field strengths derived from angular dispersion functions of dust polarization are 0.6-1.0 mG in the DR21 filament and similar to 0.1 mG in the surrounding ambient gas. The mass-to-flux ratios are found to be magnetically supercritical in the filament and slightly subcritical to nearly critical in the ambient gas. The alignment between column density structures and magnetic fields changes from random alignment in the low-density ambient gas probed by Planck to mostly perpendicular in the high-density main filament probed by James Clerk Maxwell Telescope. The magnetic field structures of the DR21 filament are in agreement with MHD simulations of a strongly magnetized medium, suggesting that magnetic fields play an important role in shaping the DR21 main filament and subfilaments.
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16.
  • Doi, Yasuo, et al. (creator_code:aut_t)
  • The JCMT BISTRO Survey: Magnetic Fields Associated with a Network of Filaments in NGC 1333
  • 2020
  • record:In_t: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 899:1
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • We present new observations of the active star formation region NGC 1333 in the Perseus molecular cloud complex from the James Clerk Maxwell Telescope B-Fields In Star-forming Region Observations (BISTRO) survey with the POL-2 instrument. The BISTRO data cover the entire NGC 1333 complex (∼1.5 pc ? 2 pc) at 0.02 pc resolution and spatially resolve the polarized emission from individual filamentary structures for the first time. The inferred magnetic field structure is complex as a whole, with each individual filament aligned at different position angles relative to the local field orientation. We combine the BISTRO data with low- and high- resolution data derived from Planck and interferometers to study the multiscale magnetic field structure in this region. The magnetic field morphology drastically changes below a scale of ∼1 pc and remains continuous from the scales of filaments (∼0.1 pc) to that of protostellar envelopes (∼0.005 pc or ∼1000 au). Finally, we construct simple models in which we assume that the magnetic field is always perpendicular to the long axis of the filaments. We demonstrate that the observed variation of the relative orientation between the filament axes and the magnetic field angles are well reproduced by this model, taking into account the projection effects of the magnetic field and filaments relative to the plane of the sky. These projection effects may explain the apparent complexity of the magnetic field structure observed at the resolution of BISTRO data toward the filament network.
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17.
  • Enfors, Sven-Olof, et al. (creator_code:aut_t)
  • Physiological responses to mixing in large scale bioreactors
  • 2001
  • record:In_t: Journal of Biotechnology. - 0168-1656 .- 1873-4863. ; 85:2, s. 175-185
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • Escherichia coli fed-batch cultivations at 22 m(3) scale were compared to corresponding laboratory scale processes and cultivations using a scale-down reactor furnished with a high-glucose concentration zone to mimic the conditions in a feed zone of the large bioreactor. Formate accumulated in the large reactor, indicating the existence of oxygen limitation zones. It is suggested that the reduced biomass yield at large scale partly is due to repeated production/reassimilation of acetate from overflow metabolism and mixed acid fermentation products due to local moving zones with oxygen limitation. The conditions that generated mixed-acid fermentation in the scale-down reactor also induced a number of stress responses, monitored by analysis of mRNA of selected stress induced genes. The stress responses were relaxed when the cells returned to the substrate limited and oxygen sufficient compartment of the reactor. Corresponding analysis in the large reactor showed that the concentration of mRNA of four stress induced genes was lowest at the sampling port most distant from the feed zone. It is assumed that repeated induction/relaxation of stress responses in a large bioreactor may contribute to altered physiological properties of the cells grown in large-scale bioreactor. Flow cytometric analysis revealed reduced damage with respect to cytoplasmic membrane potential and integrity in cells grown in the dynamic environments of the large scale reactor and the scale-down reactor.
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18.
  • Eswaraiah, Chakali, et al. (creator_code:aut_t)
  • The JCMT BISTRO Survey: Revealing the Diverse Magnetic Field Morphologies in Taurus Dense Cores with Sensitive Submillimeter Polarimetry
  • 2021
  • record:In_t: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 912:2
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • We have obtained sensitive dust continuum polarization observations at 850 μm in the B213 region of Taurus using POL-2 on SCUBA-2 at the James Clerk Maxwell Telescope as part of the B-fields in STar-forming Region Observations (BISTRO) survey. These observations allow us to probe magnetic field (B-field) at high spatial resolution (∼2000 au or ∼0.01 pc at 140 pc) in two protostellar cores (K04166 and K04169) and one prestellar core (Miz-8b) that lie within the B213 filament. Using the Davis-Chandrasekhar-Fermi method, we estimate the B-field strengths in K04166, K04169, and Miz-8b to be 38 ± 14, 44 ± 16, and 12 ± 5 μG, respectively. These cores show distinct mean B-field orientations. The B-field in K04166 is well ordered and aligned parallel to the orientations of the core minor axis, outflows, core rotation axis, and large-scale uniform B-field, in accordance with magnetically regulated star formation via ambipolar diffusion taking place in K04166. The B-field in K04169 is found to be ordered but oriented nearly perpendicular to the core minor axis and large-scale B-field and not well correlated with other axes. In contrast, Miz-8b exhibits a disordered B-field that shows no preferred alignment with the core minor axis or large-scale field. We found that only one core, K04166, retains a memory of the large-scale uniform B-field. The other two cores, K04169 and Miz-8b, are decoupled from the large-scale field. Such a complex B-field configuration could be caused by gas inflow onto the filament, even in the presence of a substantial magnetic flux.
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19.
  • Friberg, Anders, et al. (creator_code:aut_t)
  • Recognition of the Main Melody in a Polyphonic Symbolic Score using Perceptual Knowledge
  • 2009
  • record:In_t: Journal of New Music Research. - : Informa UK Limited. - 0929-8215 .- 1744-5027. ; 38:2, s. 155-169
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • It is in many cases easy for a human to identify the main melodic theme when listening to a music example. Melodic properties have been studied in several research projects, however, the differences between properties of the melody and properties of the accompaniment (non-melodic) voices have not been addressed until recently. A set of features relating to basic low-level statistical measures were selected considering general perceptual aspects. A new 'narrative' measure was designed intended to capture the amount of new unique material in each voice. The features were applied to a set of scores consisting of about 250 polyphonic ringtones consisting of MIDI versions of contemporary pop songs. All tracks were annotated into categories such as melody and accompaniment. Both multiple regression and support vector machines were applied on either the features directly or on a Gaussian transformation of the features. The resulting models predicted the correct melody in about 90% of the cases using a set of eight features. The results emphasize context as an important factor for determining the main melody. A previous version of the system has been used in a commercial system for modifying ring tones.
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20.
  • Friberg, Bertil, 1950, et al. (creator_code:aut_t)
  • One-year prospective three-center study comparing the outcome of a "soft bone implant" (prototype Mk IV) and the standard Brånemark implant.
  • 2003
  • record:In_t: Clinical implant dentistry and related research. - 1523-0899. ; 5:2, s. 71-7
  • swepub:Mat_article_t (swepub:level_refereed_t)abstract
    • BACKGROUND: Oral implant treatment ad modum Brånemark has been used for decades in the rehabilitation of edentate and partially dentate patients. Posterior jaw regions frequently exhibit bone of poor texture, and it is often difficult to obtain primary stability. Thus, it may prove beneficial to deviate from the original protocol and to use implants with a modified design, for example, with a slightly tapered geometry. PURPOSE: The purpose of the investigation was to compare the early behavior of a modified (prototype Mk IV, Brånemark System, Nobel Biocare AB, Gothenburg, Sweden; test) implant with that of the standard Brånemark implant (control) in regions of mainly type 4 bone. MATERIALS AND METHODS: Three Swedish centers participated, and a total of 44 patients were treated with oral implants for 39 maxillas and 5 mandibles. The study focused on the most distal right and left implant sites (88 implants), which were randomized to receive either a test or a control implant. Various parameters were recorded, such as registered insertion torque (OsseoCare), Nobel Biocare AB), wobbling during insertion, primary and secondary stability (as measured with resonance frequency), and marginal bone loss. The implants were followed up for 1 year. RESULTS: The test implant more frequently required a higher insertion torque and showed a significantly higher primary stability than the control implant. This difference in stability leveled out over time, and test and control implants exhibited similar secondary stability at abutment operation and at the 1-year visit. Wobbling during insertion was rarely recorded for either of the implant designs. The 1-year cumulative success rate was 93.1% for test implants and 88.4% for control implants. CONCLUSIONS: The modified implant design resulted in an increased primary stability, which may be important when placing implants in jaw regions of type 4 bone. However, independent of the achieved primary stability, successful implants tended to approach similar secondary stability in the two designs tested.
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