15 research outputs found
Nonlinear Dynamics in Distributed Systems
We build on a previous statistical model for distributed systems and
formulate it in a way that the deterministic and stochastic processes within
the system are clearly separable. We show how internal fluctuations can be
analysed in a systematic way using Van Kanpen's expansion method for Markov
processes. We present some results for both stationary and time-dependent
states. Our approach allows the effect of fluctuations to be explored,
particularly in finite systems where such processes assume increasing
importance.Comment: Two parts: 8 pages LaTeX file and 5 (uuencoded) figures in Postscript
forma
Chiral quark-soliton model in the Wigner-Seitz approximation
In this paper we study the modification of the properties of the nucleon in
the nucleus within the quark-soliton model. This is a covariant, dynamical
model, which provides a non-linear representation of the spontaneously broken
SU(2)_L X SU(2)_R symmetry of QCD. The effects of the nuclear medium are
accounted for by using the Wigner-Seitz approximation and therefore reducing
the complex many-body problem to a simpler single-particle problem. We find a
minimum in the binding energy at finite density, a change in the isoscalar
nucleon radius and a reduction of the in-medium pion decay constant. The latter
is consistent with a partial restoration of chiral symmetry at finite density,
which is predicted by other models.Comment: 30 pages, 13 figures; uses REVTeX and epsfi
Gene therapy for primary immune deficiencies: a Canadian perspective
The use of gene therapy (GT) for the treatment of primary immune deficiencies (PID) including severe combined immune deficiency (SCID) has progressed significantly in the recent years. In particular, long-term studies have shown that adenosine deaminase (ADA) gene delivery into ADA-deficient hematopoietic stem cells that are then transplanted into the patients corrects the abnormal function of the ADA enzyme, which leads to immune reconstitution. In contrast, the outcome was disappointing for patients with X-linked SCID, Wiskott–Aldrich syndrome and chronic granulomatous disease who received GT followed by autologous gene corrected transplantations, as many developed hematological malignancies. The malignancies were attributed to the predilection of the viruses used for gene delivery to integrated at oncogenic areas. The availability of safer and more efficient self-inactivating lentiviruses for gene delivery has reignited the interest in GT for many PID that are now in various stages of pre-clinical studies and clinical trials. Moreover, advances in early diagnosis of PID and gene editing technology coupled with enhanced abilities to generate and manipulate stem cells ex vivo are expected to further contribute to the benefit of GT for PID. Here we review the past, the present and the future of GT for PID, with particular emphasis on the Canadian perspective
Nucleon observables in the chiral quark-soliton model using a simple non-local approximation
The soliton of the effective chiral action in the two-point approximation
In this thesis, we study the "two-point approximation" for highly non-local
effective actions, in the particular case of the Chiral Soliton Model of the nucleon.
The nucleon in this model is regarded as being made of three valence quarks
bound together by a meson field in a soliton form. Mesons are treated in mean
field theory and the vacuum energy due to one-quark loops is included. The
theory is defined with a finite cut-off in momentum space, consistent with an
effective theory for the low-energy description of the strong interactions.
We use the two-point approximation to calculate the vacuum correction to
the chiral soliton energy for a variety of soliton profile functions, investigating
the effect of different regularisation schemes. Results are little influenced by the
choice of the cut-off, and are within 20% of exact calculations, done with the full
inclusion of the Dirac sea.
We then perform a dynamical calculation of the chiral soliton by including
sea-quark effects self-consistently in the two-point approximation. We find a
typical 20% (or less) deviation in the soliton energy from exact calculations.
We apply a further "pole" approximation which leads to a significant algebraic
simplification in the self-consistent equations. We show, in particular, that a
simple numerical fit of the pole form to the two-point cut-off function yields
essentially indistinguishable results from the latter.
We finally calculate some static nucleon observables in the two-point approximation
and find general agreement with exact calculations.
In view of the results obtained, we may hope that the pole form of the twopoint
approximation may prove to be a generally useful approach to similar problems
involving highly non-local actions.</p
A micro-level simulation for the prediction of intention and behaviour
In this contribution we aim at anchoring Agent-Based Modeling (ABM) simulations in actual models of human psychology. More specifically, we apply unidirectional ABM to social psychological models using low level agents (i.e., intra-individual) to examine whether they generate better predictions, in comparison to standard statistical approaches, concerning the intentions of performing a behavior and the behavior. Moreover, this contribution tests to what extent the predictive validity of models of attitude such as the Theory of Planned Behavior (TPB) or Model of Goal-directed Behavior (MGB) depends on the assumption that peoples’ decisions and actions are purely rational. Simulations were therefore run by considering different deviations from rationality of the agents with a trembling hand method. Two data sets concerning respectively the consumption of soft drinks and physical activity were used. Three key findings emerged from the simulations. First, compared to standard statistical approach the agent-based simulation generally improves the prediction of behavior from intention. Second, the improvement in prediction is inversely proportional to the complexity of the underlying theoretical model. Finally, the introduction of varying degrees of deviation from rationality in agents’ behavior can lead to an improvement
in the goodness of fit of the simulations. By demonstrating the potential of ABM as a complementary perspective to evaluating social psychological models, this contribution underlines the necessity of better defining agents in terms of psychological processes before examining higher levels such as the interactions between individuals
TRPC1 and TRPC3 involvement in DMD physiopathology and as potential targets for treatment in complement to rAAV-microdystrophin
International audienc
ZAP-70 restoration in mice by in vivo thymic electroporation.
International audienceViral and non-viral vectors have been developed for gene therapy, but their use is associated with unresolved problems of efficacy and safety. Efficient and safe methods of DNA delivery need to be found for medical application. Here we report a new monopolar system of non-viral electro-gene transfer into the thymus in vivo that consists of the local application of electrical pulses after the introduction of the DNA. We assessed the proof of concept of this approach by correcting ZAP-70 deficient severe combined immunodeficiency (SCID) in mice. The thymic electro-gene transfer of the pCMV-ZAP-70-IRES-EGFP vector in these mice resulted in rapid T cell differentiation in the thymus with mature lymphocytes detected by three weeks in secondary lymphoid organs. Moreover, this system resulted in the generation of long-term functional T lymphocytes. Peripheral reconstituted T cells displayed a diversified T cell receptor (TCR) repertoire, and were responsive to alloantigens in vivo. This process applied to the thymus could represent a simplified and effective alternative for gene therapy of T cell immunodeficiencies