MRI indices of functional recovery following intracerebral implantation of a human neural stem cell line in a pre-clinical model of ischaemic stroke

Stem cell therapy for ischaemic stroke is an emerging field in light of an increasing number of patients surviving with permanent disability. Several allogenic and autologous cells types are now in clinical trials with preliminary evidence of safety. Some clinical studies have reported functional improvements in some patients. After initial safety evaluation in a Phase 1 study, the conditionally immortalised human neural stem cell line CTX0E03 is currently in a Phase 2 clinical trial (PISCES-II). Previous pre-clinical studies conducted by ReNeuron Ltd, showed evidence of functional recovery in the Bilateral Asymmetry test up to 6 weeks following transplantation into rodent brain, 4 weeks after middle cerebral artery occlusion. Resting-state fMRI is increasingly used to investigate brain function in health and disease, and may also act as a predictor of recovery due to known network changes in the post-stroke recovery period. Resting-state methods have also been applied to non-human primates and rodents which have been found to have analogous resting-state networks to humans. The sensorimotor resting-state network of rodents is impaired following experimental focal ischaemia of the middle cerebral artery territory. However, the effects of stem cell implantation on brain functional networks has not previously been investigated. Prior studies assessed sensorimotor function following sub-cortical implantation of CTX0E03 cells in the rodent post-stroke brain but with no MRI assessments of functional improvements. This thesis presents research on the effect of sub-cortical implantation of CTX0E03 cells on the resting- state sensorimotor network and sensorimotor deficits in the rat following experimental stroke, using protocols based on previous work with this cell line. The work in this thesis identified functional tests of appropriate sensitivity for long-term dysfunction suitable for this laboratory, and investigated non-invasive monitoring of physiological variables required to optimize BOLD signal stability within a high-field MRI scanner. Following experimental stroke, rats demonstrated expected sensorimotor dysfunction and changes in the resting-state sensorimotor network. CTX0E03 cells did not improve post-stroke functional outcome (compared to previous studies) and with no changes in resting-state sensorimotor network activity. However, in control animals, we observed changes in functional networks due to the stereotaxic procedure. This illustrates the sensitivity of resting-state fMRI to stereotaxic procedures. We hypothesise that the damage caused by cell or vehicle implantation may have prevented functional and network recovery which has not been previously identified due to the application of different functional tests. The findings in this thesis represent one of few pre-clinical studies in resting-state fMRI network changes post-stroke and the only to date applying this technique to evaluate functional outcomes following a clinically applicable human neural stem cell treatment for ischaemic stroke. It was found that injury caused by stereotaxic injection should be taken into account when assessing the effectiveness of treatment.

A unified model for the long and high jump

A simple model based on, the maximum energy that an athlete can produce in a small time interval is used to describe the high and long jump. Conservation of angular momentum is used to explain why an athlete should, run horizontally to perform a vertical jump. Our results agree with world records. (c) 2005 American Association of Physics Teachers.

Understanding the tsunami with a simple model

In this paper, we use the approximation of shallow water waves (Margaritondo G 2005 Eur. J. Phys. 26 401) to understand the behaviour of a tsunami in a variable depth. We deduce the shallow water wave equation and the continuity equation that must be satisfied when a wave encounters a discontinuity in the sea depth. A short explanation about how the tsunami hit the west coast of India is given based on the refraction phenomenon. Our procedure also includes a simple numerical calculation suitable for undergraduate students in physics and engineering.

Model BOT partnerstwa publiczno-prywatnego w realizacji inwestycji infrastrukturalnych

Partnerstwo publiczno-prywatne zyskuje coraz większą popularność w realizacji zadań publicznych, szczególnie w obszarze inwestycji infrastrukturalnych. W toku upowszechniania wykorzystania kapitału i wiedzy pochodzącej z sektora prywatnego do realizacji inwestycji, które dotychczas były domeną sektora publicznego wykształciły się różne modele partnerstwa. Jednym z najpowszechniejszych z nich jest model BOT, czyli build, operate and transfer, co w przekładzie na język polski oznacza buduj, eksploatuj i przekaż. Już samo rozwinięcie tego skrótu, wystarcza do opisania w sposób ogólny tej koncepcji. Polega ona na wykorzystaniu potencjału gospodarczego i organizacyjnego partnera prywatnego do budowy określonego obiektu użyteczności publicznej, następnie podmiot ten odzyskuje poniesione koszty i zapewnia sobie odpowiednią stopę zysku dzięki eksploatacji tego obiektu na podstawie udzielonej mu koncesji. Po wygaśnięciu koncesji prawa do eksploatacji obiektu wracają w posiadanie podmiotu publicznego. Niniejszy artykuł ma charakter poglądowy. Autor na wstępie przybliża podstawy prawne partnerstwa oraz status prawny jego uczestników. Następnie w oparciu o regulacje prawne przedstawiony zostaje proces realizacji przedsięwzięcia BOT, po czym określane są potencjalne korzyści i koszty płynące z zastosowania tego modelu.

Brief report: preliminary proposal of a conceptual model of a digital environment for developing mathematical reasoning in students with Autism Spectrum Disorders

There is clear evidence that in typically developing children reasoning and sense-making are essential in all mathematical learning and understanding processes. In children with autism spectrum disorders (ASD), however, these become much more significant, considering their importance to successful independent living. This paper presents a preliminary proposal of a digital environment, specifically targeted to promote the development of mathematical reasoning in students with ASD. Given the diversity of ASD, the prototyping of this environment requires the study of dynamic adaptation processes and the development of activities adjusted to each user’s profile. We present the results obtained during the first phase of this ongoing research, describing a conceptual model of the proposed digital environment. Guidelines for future research are also discussed.

Signatures of doubly charged Higgs in the SU(3)(L) circle times U(1)(N) model at the CERN LHC

The scalar sector of the simplest version of the 3-3-1 electroweak model is constructed with three Higgs triplets only. We show that a relation involving two of the constants of the model, two vacuum expectation values of the neutral scalars, and the mass of the doubly charged Higgs boson leads to important information concerning the signals of this scalar particle.

Calculable lepton masses, seesaw relations, and four neutrino mixings in a 3-3-1 model with an extra U(1) symmetry

We propose a scheme in which the masses of the heavier leptons obey seesaw type relations. The light lepton masses, except the electron and the electron neutrino ones, are generated by one loop level radiative corrections. We work in a version of the 3-3-1 electroweak model that predicts singlets (charged and neutral) of heavy leptons beyond the known ones. An extra U(1)(Omega) symmetry is introduced in order to avoid the light leptons getting masses at the tree level. The electron mass induces an explicit symmetry breaking at U(1)(Omega). We discuss also the mixing matrix among four neutrinos. The new energy scale required is not higher than a few TeV.

Searching for doubly charged Higgs bosons at the LHC in a 3-3-1 model

Using a peculiar version of the SU(3)(L) circle times U(1)(N) electroweak model, we investigate the production of doubly charged Higgs boson at the Large Hadron Collider. Our results include branching ratio calculations for the doubly charged Higgs and for one of the neutral scalar bosons of the model. (c) 2006 Elsevier B.V. All rights reserved.

Singlet extensions of the standard model at LHC Run 2: benchmarks and comparison with the NMSSM

The Complex singlet extension of the Standard Model (CxSM) is the simplest extension that provides scenarios for Higgs pair production with different masses. The model has two interesting phases: the dark matter phase, with a Standard Model-like Higgs boson, a new scalar and a dark matter candidate; and the broken phase, with all three neutral scalars mixing. In the latter phase Higgs decays into a pair of two different Higgs bosons are possible. In this study we analyse Higgs-to-Higgs decays in the framework of singlet extensions of the Standard Model (SM), with focus on the CxSM. After demonstrating that scenarios with large rates for such chain decays are possible we perform a comparison between the NMSSM and the CxSM. We find that, based on Higgs-to-Higgs decays, the only possibility to distinguish the two models at the LHC run 2 is through final states with two different scalars. This conclusion builds a strong case for searches for final states with two different scalars at the LHC run 2. Finally, we propose a set of benchmark points for the real and complex singlet extensions to be tested at the LHC run 2. They have been chosen such that the discovery prospects of the involved scalars are maximised and they fulfil the dark matter constraints. Furthermore, for some of the points the theory is stable up to high energy scales. For the computation of the decay widths and branching ratios we developed the Fortran code sHDECAY, which is based on the implementation of the real and complex singlet extensions of the SM in HDECAY.

Neutral Higgs bosons in the SU(3)(L)circle times U(1)(N) model

The SU(3)(L)circle times U(1)(N) electroweak model predicts new Higgs bosons beyond the one of the standard model. In this work we investigate the signature and production of neutral SU(3)(L)circle times U(1)(N) Higgs bosons in the e(-)e(+) Next Linear Collider and in the CERN Linear Collider . We compute the branching ratios of two of the SU(3)(L)circle times U(1)(N) neutral Higgs bosons and study the possibility to detect them and the Z' extra neutral boson of the model.