1,481 research outputs found
Oscillation patterns in negative feedback loops
Organisms are equipped with regulatory systems that display a variety of
dynamical behaviours ranging from simple stable steady states, to switching and
multistability, to oscillations. Earlier work has shown that oscillations in
protein concentrations or gene expression levels are related to the presence of
at least one negative feedback loop in the regulatory network. Here we study
the dynamics of a very general class of negative feedback loops. Our main
result is that in these systems the sequence of maxima and minima of the
concentrations is uniquely determined by the topology of the loop and the
activating/repressing nature of the interaction between pairs of variables.
This allows us to devise an algorithm to reconstruct the topology of
oscillating negative feedback loops from their time series; this method applies
even when some variables are missing from the data set, or if the time series
shows transients, like damped oscillations. We illustrate the relevance and the
limits of validity of our method with three examples: p53-Mdm2 oscillations,
circadian gene expression in cyanobacteria, and cyclic binding of cofactors at
the estrogen-sensitive pS2 promoter.Comment: 10 pages, 8 figure
Growth, profits and technological choice: The case of the Lancashire cotton textile industry
Using Lancashire textile industry company case studies and financial records, mainly from the period just before the First World War, the processes of growth and decline are re-examined. These are considered by reference to the nature of Lancashire entrepreneurship and the impact on technological choice. Capital accumulation, associated wealth distributions and the character of Lancashire business organisation were sybiotically linked to the success of the industry before 1914. However, the legacy of that accumulation in later decades, chronic overcapacity, formed a barrier to reconstruction and enhanced the preciptious decline of a once great industry
Non-equilibrium stationary state of a two-temperature spin chain
A kinetic one-dimensional Ising model is coupled to two heat baths, such that
spins at even (odd) lattice sites experience a temperature ().
Spin flips occur with Glauber-type rates generalised to the case of two
temperatures. Driven by the temperature differential, the spin chain settles
into a non-equilibrium steady state which corresponds to the stationary
solution of a master equation. We construct a perturbation expansion of this
master equation in terms of the temperature difference and compute explicitly
the first two corrections to the equilibrium Boltzmann distribution. The key
result is the emergence of additional spin operators in the steady state,
increasing in spatial range and order of spin products. We comment on the
violation of detailed balance and entropy production in the steady state.Comment: 11 pages, 1 figure, Revte
Ex post aggregate real rates of return in Canada: 1947-1976
Cover title"June 1981."Series statement handwritten on cover"This is a draft of a study to be published by the Economic Council of Canada. It is made available to participants in the Rates of Return Conference on the strict understanding that it is not to be circulated or quoted without permission from the Economic Council of Canada."Includes bibliographical references (p. 77-80
Novel chimerized IgA CD20 antibodies : Improving neutrophil activation against CD20-positive malignancies
ABSTRACT Current combination therapies elicit high response rates in B cell malignancies, often using CD20 antibodies as the backbone of therapy. However, many patients eventually relapse or develop progressive disease. Therefore, novel CD20 antibodies combining multiple effector mechanisms were generated. To study whether neutrophil-mediated destruction of B cell malignancies can be added to the arsenal of effector mechanisms, we chimerized a panel of five previously described murine CD20 antibodies to the human IgG1, IgA1 and IgA2 isotype. Of this panel, we assessed in vitro antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and direct cell death induction capacity and studied the efficacy in two different in vivo mouse models. IgA antibodies outperformed IgG1 antibodies in neutrophil-mediated killing in vitro, both against CD20-expressing cell lines and primary patient material. In these assays, we observed loss of CD19 with both IgA and IgG antibodies. Therefore, we established a novel method to improve the assessment of B-cell depletion by CD20 antibodies by including CD24 as a stable cell marker. Subsequently, we demonstrated that only IgA antibodies were able to reduce B cell numbers in this context. Additionally, IgA antibodies showed efficacy in both an intraperitoneal tumor model with EL4 cells expressing huCD20 and in an adoptive transfer model with huCD20-expressing B cells. Taken together, we show that IgA, like IgG, can induce ADCC and CDC, but additionally triggers neutrophils to kill (malignant) B cells. We conclude that antibodies of the IgA isotype offer an attractive repertoire of effector mechanisms for the treatment of CD20-expressing malignancies.Peer reviewe
Integrate and Fire Neural Networks, Piecewise Contractive Maps and Limit Cycles
We study the global dynamics of integrate and fire neural networks composed
of an arbitrary number of identical neurons interacting by inhibition and
excitation. We prove that if the interactions are strong enough, then the
support of the stable asymptotic dynamics consists of limit cycles. We also
find sufficient conditions for the synchronization of networks containing
excitatory neurons. The proofs are based on the analysis of the equivalent
dynamics of a piecewise continuous Poincar\'e map associated to the system. We
show that for strong interactions the Poincar\'e map is piecewise contractive.
Using this contraction property, we prove that there exist a countable number
of limit cycles attracting all the orbits dropping into the stable subset of
the phase space. This result applies not only to the Poincar\'e map under
study, but also to a wide class of general n-dimensional piecewise contractive
maps.Comment: 46 pages. In this version we added many comments suggested by the
referees all along the paper, we changed the introduction and the section
containing the conclusions. The final version will appear in Journal of
Mathematical Biology of SPRINGER and will be available at
http://www.springerlink.com/content/0303-681
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Ensemble prediction for nowcasting with a convection-permitting model—I: description of the system and the impact of radar-derived surface precipitation rates
A key strategy to improve the skill of quantitative predictions of precipitation, as well as hazardous weather such as severe thunderstorms and flash floods is to exploit the use of observations of convective activity (e.g. from radar). In this paper, a convection-permitting ensemble prediction system (EPS) aimed at addressing the problems of forecasting localized weather events with relatively short predictability time scale and based on a 1.5 km grid-length version of the Met Office Unified Model is presented. Particular attention is given to the impact of using predicted observations of radar-derived precipitation intensity in the ensemble transform Kalman filter (ETKF) used within the EPS. Our initial results based on the use of a 24-member ensemble of forecasts for two summer case studies show that the convective-scale EPS produces fairly reliable forecasts of temperature, horizontal winds and relative humidity at 1 h lead time, as evident from the inspection of rank histograms. On the other hand, the rank histograms seem also to show that the EPS generates too much spread for forecasts of (i) surface pressure and (ii) surface precipitation intensity. These may indicate that for (i) the value of surface pressure observation error standard deviation used to generate surface pressure rank histograms is too large and for (ii) may be the result of non-Gaussian precipitation observation errors. However, further investigations are needed to better understand these findings. Finally, the inclusion of predicted observations of precipitation from radar in the 24-member EPS considered in this paper does not seem to improve the 1-h lead time forecast skill
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