12 research outputs found
Mesoscopic models for DNA stretching under force: new results and comparison to experiments
Single molecule experiments on B-DNA stretching have revealed one or two
structural transitions, when increasing the external force. They are
characterized by a sudden increase of DNA contour length and a decrease of the
bending rigidity. It has been proposed that the first transition, at forces of
60--80 pN, is a transition from B to S-DNA, viewed as a stretched duplex DNA,
while the second one, at stronger forces, is a strand peeling resulting in
single stranded DNAs (ssDNA), similar to thermal denaturation. But due to
experimental conditions these two transitions can overlap, for instance for
poly(dA-dT). We derive analytical formula using a coupled discrete worm like
chain-Ising model. Our model takes into account bending rigidity, discreteness
of the chain, linear and non-linear (for ssDNA) bond stretching. In the limit
of zero force, this model simplifies into a coupled model already developed by
us for studying thermal DNA melting, establishing a connexion with previous
fitting parameter values for denaturation profiles. We find that: (i) ssDNA is
fitted, using an analytical formula, over a nanoNewton range with only three
free parameters, the contour length, the bending modulus and the monomer size;
(ii) a surprisingly good fit on this force range is possible only by choosing a
monomer size of 0.2 nm, almost 4 times smaller than the ssDNA nucleobase
length; (iii) mesoscopic models are not able to fit B to ssDNA (or S to ss)
transitions; (iv) an analytical formula for fitting B to S transitions is
derived in the strong force approximation and for long DNAs, which is in
excellent agreement with exact transfer matrix calculations; (v) this formula
fits perfectly well poly(dG-dC) and -DNA force-extension curves with
consistent parameter values; (vi) a coherent picture, where S to ssDNA
transitions are much more sensitive to base-pair sequence than the B to S one,
emerges.Comment: 14 pages, 9 figure
Denominators in cluster algebras of affine type
The Fomin-Zelevinsky Laurent phenomenon states that every cluster variable in
a cluster algebra can be expressed as a Laurent polynomial in the variables
lying in an arbitrary initial cluster. We give representation-theoretic
formulas for the denominators of cluster variables in cluster algebras of
affine type. The formulas are in terms of the dimensions of spaces of
homomorphisms in the corresponding cluster category, and hold for any choice of
initial cluster.Comment: 22 pages, no figures. Correction to Defn 1.2. Minor correction
Immune mechanisms in malaria: new insights in vaccine development.
Early data emerging from the first phase 3 trial of a malaria vaccine are raising hopes that a licensed vaccine will soon be available for use in endemic countries, but given the relatively low efficacy of the vaccine, this needs to be seen as a major step forward on the road to a malaria vaccine rather than as arrival at the final destination. The focus for vaccine developers now moves to the next generation of malaria vaccines, but it is not yet clear what characteristics these new vaccines should have or how they can be evaluated. Here we briefly review the epidemiological and immunological requirements for malaria vaccines and the recent history of malaria vaccine development and then put forward a manifesto for future research in this area. We argue that rational design of more effective malaria vaccines will be accelerated by a better understanding of the immune effector mechanisms involved in parasite regulation, control and elimination