A New Source of Stem Cells in Amniotic Fluid and Placenta in 1st Trimester of Pregnancy

Mesenchymal stromal cells (MSC) are multipotent cells found in fetal, neonatal and adult tissues. Fetal MSC have advantageous characteristics over their adult counterparts, and the regenerative potential of fetal blood MSC has recently been shown in a model of skeletal dysplasia and renal failure. Although fetal blood MSC can be isolated during ongoing pregnancy, the clinical effectiveness of using fetal blood-derived MSC for prenatal fetal cell therapy is constrained by the invasive nature of blood sampling procedure. With amniocentesis and chorionic villus sampling (CVS), fetal MSC can be obtained with minimal invasion. The aim of this study was to characterise stem cells from 1st trimester amniotic fluid (AF) and placenta by comparing their phenotype with MSC from 1st trimester bone marrow and 2nd trimester AF. Cells from all sources have similar immunophenotype, express pluripotency markers and telomerase, but 1st trimester AF stem cells have higher kinetics. The cells can differentiate into 3 lineages (bone, fat and cartilage), form embryoid bodies (EB) in vitro and can be transfected with high efficiency using non-viral methods. The migration potential of fetal MSC was also investigated using in vitro migration assays, to recapitulate the in vivo mechanisms involved in donor cell recruitment to various tissues and delineate the pathways involved. Fetal blood MSC and AF stem cells were shown to express CXCR4, the stromal cell-derived factor-1 (SDF-1) receptor, intracellularly but not on the cell membrane and migrate to SDF-1 gradients and to osteoblast cultures derived from the Osteogenesis Imperfecta mouse (oim), but not wild type bones. Pre-stimulation with oim plasma up-regulated CXCR4 and increased chemotaxis to SDF-1 and oim bone. Conclusively, 1st trimester AF and placenta are a new source of stem cells with great potential for future cell therapy applications. Also, initial experiments indicate the importance of the SDF-1/CXCR4 axis for stem cell recruitment to the site of injury

Spontaneously quenched gamma-ray spectra from compact sources

We study a mechanism for producing intrinsic broken power-law gamma-ray spectra in compact sources. This is based on the principles of automatic photon quenching, according to which, gamma-rays are being absorbed on spontaneously produced soft photons, whenever the injected luminosity in gamma-rays lies above a certain critical value. We derive an analytical expression for the critical gamma-ray compactness in the case of power-law injection. For the case where automatic photon quenching is relevant, we calculate analytically the emergent steady-state gamma-ray spectra. We perform also numerical calculations in order to back up our analytical results. We show that a spontaneously quenched power-law gamma-ray spectrum obtains a photon index 3{\Gamma}/2, where {\Gamma} is the photon index of the power-law at injection. Thus, large spectral breaks of the gamma-ray photon spectrum, e.g. $\Delta \Gamma \gtrsim 1$, can be obtained by this mechanism. We also discuss additional features of this mechanism that can be tested observationally. Finally, we fit the multiwavelength spectrum of a newly discovered blazar (PKS 0447-439) by using such parameters, as to explain the break in the gamma-ray spectrum by means of spontaneous photon quenching, under the assumption that its redshift lies in the range 0.1<z<0.24.Comment: 14 pages, 9 figures, 2 tables, accepted for publication in A&

Classes of Measures Generated by Capacities

We introduce classes of measures in the half-space $\mathbf{R}^{n+1}_+,$ generated by Riesz, or Bessel, or Besov capacities in $\mathbf{R}^n$, and give a geometric characterization as Carleson-type measures

A self-organized criticality model for ion temperature gradient (ITG) mode driven turbulence in confined plasma

A new Self-Organized Criticality (SOC) model is introduced in the form of a Cellular Automaton (CA) for ion temperature gradient (ITG) mode driven turbulence in fusion plasmas. Main characteristics of the model are that it is constructed in terms of the actual physical variable, the ion temperature, and that the temporal evolution of the CA, which necessarily is in the form of rules, mimics actual physical processes as they are considered to be active in the system, i.e. a heating process and a local diffusive process that sets on if a threshold in the normalized ion temperature gradient R/L_T is exceeded. The model reaches the SOC state and yields ion temperature profiles of exponential shape, which exhibit very high stiffness, in that they basically are independent of the loading pattern applied. This implies that there is anomalous heat transport present in the system, despite the fact that diffusion at the local level is imposed to be of a normal kind. The distributions of the heat fluxes in the system and of the heat out-fluxes are of power-law shape. The basic properties of the model are in good qualitative agreement with experimental results.Comment: In press at Physics of Plasmas, July 2010; 11 pages, 5 figure

The role of oxidative stress in photoreceptor degeneration

Reactive oxygen species (ROS) are constitutively produced by mitochondria and represent the major cellular source of oxidative stress. ROS are capable of attacking molecules such as DNA, proteins and lipids, and of compromising either the structural and functional integrity or the survival of cells. Mitochondria also play a key role in apoptosis, the major mechanism of cell death in retinitis pigmentosa (RP), which is a diverse group of inherited human retinal dystrophies associated with progressive degeneration of photoreceptor cells. Mutations in numerous genes have been implicated in RP, which have distinct pathophysiological mechanisms and lead to retinal degeneration at different rates. The aim of this thesis was to investigate the role of oxidative stress in disease progression using mouse models of human RP.The mouse mutants retinal degeneration 1 (rdl/rdl), atypical retinal degeneration 1 (atrdl/atrdl), rhodopsin knockout (R/?c/ ~) and peripherin/retinal degeneration slow (rds/rds) were firstly investigated for evidence of oxidative damage by analysis of oxidative stress markers. Secondly, the mutants were crossed to a superoxide dismutase 2 heterozygous mouse (Sod2+/~), with decreased mitochondrial antioxidant activity, to examine the effect on disease progression. Thirdly, mutants were treated with a mitochondrially targeted ubiquinone derivative (MitoQ), which is a powerful antioxidant, to try and slow the rate of retinal degeneration. MitoQ was administered orally during pregnancy and for an extended postnatal period and uptake, toxicity, breeding behaviour and survival were assessed. Rates of photoreceptor degeneration were estimated by morphometric and apoptosis assays, while the cellular redox status was assessed by glutathione assays and by measuring the activities of the mitochondrial enzymes NADH:ubiquinone oxidoreductase (complex I), which is oxidative stress-sensitive, compared with citrate synthase, which is oxidative stressinsensitive.All retinal degeneration mutants were found to show significantly reduced complex I activities, while citrate synthase was unchanged, indicating mitochondrial oxidative stress. Rates of photoreceptor degeneration were unchanged either by crossing to a Sod2+' genetic background or by MitoQ administration. Only the rds/rds mutant, with the slowest rate of degeneration, showed a significant increase in complex I activity after MitoQ administration. Although mitochondrial oxidative stress is shown to be present in all of the retinal degeneration mutants, altering the oxidative status of the retina had no effect on photoreceptor survival

Data efficiency in imitation learning with a focus on object manipulation

Imitation is a natural human behaviour that helps us learn new skills. Modelling this behaviour in robots, however, has many challenges. This thesis investigates the challenge of handling the expert demonstrations in an efficient way, so as to minimise the number of demonstrations required for robots to learn. To achieve this, it focuses on demonstration data efficiency at various steps of the imitation process. Specifically, it presents new methodologies that offer ways to acquire, augment and combine demonstrations in order to improve the overall imitation process. Firstly, the thesis explores an inexpensive and non-intrusive way of acquiring dexterous human demonstrations. Human hand actions are quite complex, especially when they involve object manipulation. The proposed framework tackles this by using a camera to capture the hand information and then retargeting it to a dexterous hand model. It does this by combining inverse kinematics with stochastic optimisation. The demonstrations collected with this framework can then be used in the imitation process. Secondly, the thesis presents a novel way to apply data augmentation to demonstrations. The main difficulty of augmenting demonstrations is that their trajectorial nature can make them unsuccessful. Whilst previous works require additional knowledge about the task or demonstrations to achieve this, this method performs augmentation automatically. To do this, it introduces a correction network that corrects the augmentations based on the distribution of the original experts. Lastly, the thesis investigates data efficiency in a multi-task scenario where it additionally proposes a data combination method. Its aim is to automatically divide a set of tasks into sub-behaviours. Contrary to previous works, it does this without any additional knowledge about the tasks. To achieve this, it uses both task-specific and shareable modules. This minimises negative transfer and allows for the method to be applied to various task sets with different commonalities.Open Acces