| 1. |
- Mandenius, Carl-Fredrik, et al.
(författare)
-
Toward Preclinical Predictive Drug Testing for Metabolism and Hepatotoxicity by Using In Vitro Models Derived from Human Embryonic Stem Cells and Human Cell Lines - A Report on the Vitrocellomics EU-project
- 2011
-
Ingår i: ATLA-ALTERNATIVES TO LABORATORY ANIMALS. - : Fund for Replacement of Animals in Medical Experiments; 1999. - 0261-1929 .- 2632-3559. ; 39:2, s. 147-171
-
Tidskriftsartikel (refereegranskat)abstract
- Drug-induced liver injury is a common reason for drug attrition in late clinical phases, and even for post-launch withdrawals. As a consequence, there is a broad consensus in the pharmaceutical industry, and within regulatory authorities, that a significant improvement of the current in vitro test methodologies for accurate assessment and prediction of such adverse effects is needed. For this purpose, appropriate in vivo-like hepatic in vitro models are necessary, in addition to novel sources of human hepatocytes. In this report, we describe recent and ongoing research toward the use of human embryonic stem cell (hESC)-derived hepatic cells, in conjunction with new and improved test methods, for evaluating drug metabolism and hepatotoxicity. Recent progress on the directed differentiation of human embryonic stem cells to the functional hepatic phenotype is reported, as well as the development and adaptation of bioreactors and toxicity assay technologies for the testing of hepatic cells. The aim of achieving a testing platform for metabolism and hepatotoxicity assessment, based on hESC-derived hepatic cells, has advanced markedly in the last 2-3 years. However, great challenges still remain, before such new test systems could be routinely used by the industry. In particular, we give an overview of results from the Vitrocellomics project (EU Framework 6) and discuss these in relation to the current state-of-the-art and the remaining difficulties, with suggestions on how to proceed before such in vitro systems can be implemented in industrial discovery and development settings and in regulatory acceptance.
|
|
| 2. |
|
|
| 3. |
- Barucca, G., et al.
(författare)
-
Study of excited Ξ baryons with the P¯ ANDA detector
- 2021
-
Ingår i: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
-
Tidskriftsartikel (refereegranskat)abstract
- The study of baryon excitation spectra provides insight into the inner structure of baryons. So far, most of the world-wide efforts have been directed towards N∗ and Δ spectroscopy. Nevertheless, the study of the double and triple strange baryon spectrum provides independent information to the N∗ and Δ spectra. The future antiproton experiment P¯ANDA will provide direct access to final states containing a Ξ¯ Ξ pair, for which production cross sections up to μb are expected in p¯p reactions. With a luminosity of L= 10 31 cm- 2 s- 1 in the first phase of the experiment, the expected cross sections correspond to a production rate of ∼106events/day. With a nearly 4 π detector acceptance, P¯ANDA will thus be a hyperon factory. In this study, reactions of the type p¯p → Ξ¯ +Ξ∗ - as well as p¯p → Ξ¯ ∗ +Ξ- with various decay modes are investigated. For the exclusive reconstruction of the signal events a full decay tree fit is used, resulting in reconstruction efficiencies between 3 and 5%. This allows high statistics data to be collected within a few weeks of data taking.
|
|
| 4. |
- Barucca, G., et al.
(författare)
-
The potential of Λ and Ξ- studies with PANDA at FAIR
- 2021
-
Ingår i: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
-
Tidskriftsartikel (refereegranskat)abstract
- The antiproton experiment PANDA at FAIR is designed to bring hadron physics to a new level in terms of scope, precision and accuracy. In this work, its unique capability for studies of hyperons is outlined. We discuss ground-state hyperons as diagnostic tools to study non-perturbative aspects of the strong interaction, and fundamental symmetries. New simulation studies have been carried out for two benchmark hyperon-antihyperon production channels: p¯ p→ Λ¯ Λ and p¯ p→ Ξ¯ +Ξ-. The results, presented in detail in this paper, show that hyperon-antihyperon pairs from these reactions can be exclusively reconstructed with high efficiency and very low background contamination. In addition, the polarisation and spin correlations have been studied, exploiting the weak, self-analysing decay of hyperons and antihyperons. Two independent approaches to the finite efficiency have been applied and evaluated: one standard multidimensional efficiency correction approach, and one efficiency independent approach. The applicability of the latter was thoroughly evaluated for all channels, beam momenta and observables. The standard method yields good results in all cases, and shows that spin observables can be studied with high precision and accuracy already in the first phase of data taking with PANDA.
|
|
| 5. |
- Bengtsson, Johan, 1985, et al.
(författare)
-
Metaxa: Automated detection and discrimination among ribosomal small subunit (12S/16S/18S) sequences of archaea, bacteria, eukaryotes, mitochondria, and chloroplasts
- 2011
-
Ingår i: SocBiN Bioinformatics Conference, Helsinki, Finland, 2011.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The ribosomal small subunit (SSU) rRNA gene has emerged as an important genetic marker for taxonomic identification in environmental sequencing datasets. However, the gene is not only present in the nuclear genome of eukaryotes and the core genome of prokaryotes, but also in the mitochondria and chloroplasts of eukaryotes. The SSU genes in the core genome, mitochondria and chloroplast are conceptually paralogous and should in most situations not be aligned and analyzed jointly, e.g. when estimating species diversity. Identifying the origin of SSU sequences in complex sequence datasets is a time-consuming and largely manual undertaking. To ease this situation, we have created Metaxa, an automated software tool to extract full-length and partial SSU sequences from larger sequence datasets and assign them to an archaeal, bacte- rial, nuclear eukaryote, mitochondrial, or chloroplast origin. Metaxa very efficiently detects SSU sequences from fragments as short as 200 base pairs, and correctly classifies 97% of the identified genes at read lengths typically obtained from pyrosequencing. In addition, Metaxa shows a false positive rate of 0.00012% when run on random DNA fragments, showing the robustness of the method. We believe that this tool will be useful in microbial and evolutionary ecology as well as in metagenomics.
|
|
| 6. |
- Bengtsson-Palme, Johan, 1985, et al.
(författare)
-
Metaxa: a software tool for automated detection and discrimination among ribosomal small subunit (12S/16S/18S) sequences of archaea, bacteria, eukaryotes, mitochondria, and chloroplasts in metagenomes and environmental sequencing datasets
- 2011
-
Ingår i: Antonie van Leeuwenhoek: international journal of general and molecular microbiology. - : Springer Science and Business Media LLC. - 0003-6072 .- 1572-9699. ; 100:3, s. 471-475
-
Tidskriftsartikel (refereegranskat)abstract
- The ribosomal small subunit (SSU) rRNA gene has emerged as an important genetic marker for taxonomic identification in environmental sequencing datasets. In addition to being present in the nucleus of eukaryotes and the core genome of prokaryotes, the gene is also found in the mitochondria of eukaryotes and in the chloroplasts of photosynthetic eukaryotes. These three sets of genes are conceptually paralogous and should in most situations not be aligned and analyzed jointly. To identify the origin of SSU sequences in complex sequence datasets has hitherto been a time-consuming and largely manual undertaking. However, the present study introduces Metaxa (http://microbiology.se/software/metaxa/), an automated software tool to extract full-length and partial SSU sequences from larger sequence datasets and assign them to an archaeal, bacterial, nuclear eukaryote, mitochondrial, or chloroplast origin. Using data from reference databases and from full-length organelle and organism genomes, we show that Metaxa detects and scores SSU sequences for origin with very low proportions of false positives and negatives. We believe that this tool will be useful in microbial and evolutionary ecology as well as in metagenomics.
|
|
| 7. |
- Egenvall, Agneta, et al.
(författare)
-
Rein tension in harness trotters during on-track exercise
- 2022
-
Ingår i: Frontiers in Veterinary Science. - : Frontiers Media SA. - 2297-1769. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Horseracing is under public scrutiny with increasing demands to safeguard horse welfare. It is accepted that, as a result of bit pressure and/or equipment, mouth lesions accompany many types of horse use, including racing. However, there are currently no data available on the range of bit pressures in driven trotters. Our aim was to investigate whether rein tension (RT, proxy for bit pressures) differs among gaits, between tempo within gait, between horses and drivers, and between left/right reins. Standardbreds (n = 9), driven by experienced drivers (n = 11), performed exercise tests on a racetrack (cross-over design; total 31 tests, data available from 26 tests). Horses' motion symmetry was measured before tests (trotting in hand). Rein tension, speed and heart rate were measured during exercise. A moving-window filter was applied to RT raw data. Median, maximum and interquartile range for the estimated stride median RT were determined for each rein (left/right) and segment: walk; circling in slow trot followed by transition to faster trot; fast (racing) trot; and slowing down to walk. Mixed models were used for statistical analysis. Least square means for segment median RT ranged between 17–19 N in walk, 34–40 N during circling-accelerating, 51–62 N in fast trot, and 53–71 N for slowing down. Segment maximum RT was between 60–81 N in walk, 104–106 N during circling-accelerating, 72–86 N in fast trot, and 86–129 N during slowing down. Interquartile ranges were between 7–9 N in walk, 28–31 N during circling-accelerating, 8–10 N in fast trot, and 12–18 N for slowing down. Hind limb asymmetry exceeded the recommended threshold in three horses and was associated with higher median (48 N) and maximum (106 N) RT than symmetric horses (29 N and 73 N, respectively, p < 0.01). Consistent left-right asymmetry in RT was more common among horses than among drivers. Rein tension increased with increasing heart rate (p ≤ 0.0006). Rein tensions were higher than those reported during riding or in horses worked from the ground. The findings of high RT, taken together with the high reported prevalence of oral injuries in harness trotters, call for further research into RT, motion symmetry and use of equipment.
|
|
| 8. |
- Fakhardji, Wissam, 1990-
(författare)
-
Classical molecular dynamics simulations of collision-induced absorption : method development and evaluation
- 2021
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis collision-induced absorption (CIA) coefficients are computed using molec-ular dynamics (MD) simulations. Part I is dedicated to the theoretical frame of the method, from the classical theory radiation to the derivation of an absorption coefficient. The second part is a on the implementation of the method in the in-house software Spa-CIAL (Spectra of Collision-Induced Absorption with LAMMPS). This package is split in two parts: the molecular dynamics part being treated with the open source package LAMMPS, and the post-processing for the computation of the collision-induced absorp-tion with a Python code. The post-processing has been developed in two distinct ways each of them presenting different properties. The first one, based on what has been done previously, is designed to compute the dipole auto-correlation function (ACF) to obtain the CIA spectra after Fourier transformation. Many improvements has been made like the time averaging method is used in order to considerably increase the statistics requiring reasonable resource needs. The use of the fast Fourier transform algorithm (FFT) and the apodization procedure are also used for better accuracy of the results. The reformulation of the equations, especially with the Wiener-Kintchine (WK) theorem, gives a completely new implementation for which the CPU intensive computation of the dipole ACF is no longer needed. Instead, the contributions to the CIA spectrum are computed for each pair separately. In addition to improve significantly the performance of the code, it is now possible to separate the free-free and the bound-bound contributions. The comparison with the previous method (ACF) for the Ar-Xe system has shown a good accordance thus validating this new implementation. This great progress paves the way for the classical study of the dimers features in the absorption coefficient. The programs developed in this work can be adapted to handle molecular gas mixtures that are relevant in studies of radiative transfer in planetary atmospheres.
|
|
| 9. |
- Hansen, Lea B.S., et al.
(författare)
-
A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults
- 2018
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- © 2018, The Author(s). Adherence to a low-gluten diet has become increasingly common in parts of the general population. However, the effects of reducing gluten-rich food items including wheat, barley and rye cereals in healthy adults are unclear. Here, we undertook a randomised, controlled, cross-over trial involving 60 middle-aged Danish adults without known disorders with two 8-week interventions comparing a low-gluten diet (2 g gluten per day) and a high-gluten diet (18 g gluten per day), separated by a washout period of at least six weeks with habitual diet (12 g gluten per day). We find that, in comparison with a high-gluten diet, a low-gluten diet induces moderate changes in the intestinal microbiome, reduces fasting and postprandial hydrogen exhalation, and leads to improvements in self-reported bloating. These observations suggest that most of the effects of a low-gluten diet in non-coeliac adults may be driven by qualitative changes in dietary fibres.
|
|
| 10. |
- Hartmann, Elke, et al.
(författare)
-
Associations between driving rein tensions and drivers’ reports of the behaviour and driveability of Standardbred trotters
- 2022
-
Ingår i: Applied Animal Behaviour Science. - : Elsevier BV. - 0168-1591 .- 1872-9045. ; 254
-
Tidskriftsartikel (refereegranskat)abstract
- Effective communication between driver and horse through the reins is essential in harness racing to promote safety and optimise performance. Yet, the magnitudes of rein tension applied to driven horses, particularly Standardbred trotters (ST) are currently poorly understood. This is surprising given the number of reports that speak of mouth lesions after competition and equipment use that give raise to horse welfare concerns. Combining rein tension measurements with behavioural parameters has the potential to characterize “driveability” (as compared to “rideability”, the equivalent industry term for riding horses). Thus, the aims of the current study were: (i) identify how drivers perceive ST's behavioural reactions in response to rein signals when driven on a racetrack, (ii) investigate whether drivers’ subjective appraisals of horses’ behavioural responses align with measured rein tensions (RT), (iii) relate these appraisals to the horses’ perceived driveability (score 1 = poor, 10 = excellent), and (iv) assess whether drivers differ in their scoring of horses’ driveability. Nine ST (5 geldings, 7.8 mean ± 2.1 SE years; 4 mares, 6.8 ± 0.5) were driven by 11 drivers (7 females; 4 males) all of whom were experienced in driving ST. Nine drivers tested three different horses each, and two drivers drove two of the horses. This resulted in 31 test drives involving several segments, each comprising a series of changes of gait and direction of travel. Rein tension meters were used throughout. After each test, drivers were asked to report on their experience of each horse they had just driven and to estimate RT (continuous rating scale from 0 to 50 kg) while driving that horse. Overall, segment had a significant effect on median RT (P < 0.001), with RT rising significantly in racing trot (average 59 N; Trot Left/Trot Right) than trotting on a circle (23 N; Circle Left/Circle Right) and walking (8 N), and was higher in counter-clockwise than in clockwise direction in racing trot (P = 0.058). Furthermore, there was an alignment between recorded RT and drivers’ estimates of perceived RT (P < 0.001), and driveability scores increased when estimated RT increased. The current study has confirmed that rein tensiometry may have a place in providing an evidence-base for consistent rein use, especially when horses are driven by multiple drivers. Whether or not soft tissue damage after competitive racing is correlated to higher peak RT, caused by the use of harsher equipment, or a combination of both, merits further investigation.
|
|
