1,063 research outputs found
Hsp-90 and the biology of nematodes
BACKGROUND: Hsp-90 from the free-living nematode Caenorhabditis elegans is unique in that it fails to bind to the specific Hsp-90 inhibitor, geldanamycin (GA). Here we surveyed 24 different free-living or parasitic nematodes with the aim of determining whether C. elegans Hsp-90 was the exception or the norm amongst the nematodes. We combined these data with codon evolution models in an attempt to identify whether hsp-90 from GA-binding and non-binding species has evolved under different evolutionary constraints.<BR/>RESULTS: We show that GA-binding is associated with life history: free-living nematodes and those parasitic species with free-living larval stages failed to bind GA. In contrast, obligate parasites and those worms in which the free-living stage in the environment is enclosed within a resistant egg, possess a GA-binding Hsp-90. We analysed Hsp-90 sequences from fifteen nematode species to determine whether nematode hsp-90s have undergone adaptive evolution that influences GA-binding. Our data provide evidence of rapid diversifying selection in the evolution of the hsp-90 gene along three separate lineages, and identified a number of residues showing significant evidence of adaptive evolution. However, we were unable to prove that the selection observed is correlated with the ability to bind geldanamycin or not.<BR/>CONCLUSION: Hsp-90 is a multi-functional protein and the rapid evolution of the hsp-90 gene presumably correlates with other key cellular functions. Factors other than primary amino acid sequence may influence the ability of Hsp-90 to bind to geldanamycin
Calculations of Neutron Reflectivity in the eV Energy Range from Mirrors made of Heavy Nuclei with Neutron-Nucleus Resonances
We evaluate the reflectivity of neutron mirrors composed of certain heavy
nuclei which possess strong neutron-nucleus resonances in the eV energy range.
We show that the reflectivity of such a mirror for some nuclei can in principle
be high enough near energies corresponding to compound neutron-nucleus
resonances to be of interest for certain scientific applications in
non-destructive evaluation of subsurface material composition and in the theory
of neutron optics beyond the kinematic limit.Comment: 18 pages, 5 figures, 1 tabl
Cutting and Shuffling a Line Segment: Mixing by Interval Exchange Transformations
We present a computational study of finite-time mixing of a line segment by
cutting and shuffling. A family of one-dimensional interval exchange
transformations is constructed as a model system in which to study these types
of mixing processes. Illustrative examples of the mixing behaviors, including
pathological cases that violate the assumptions of the known governing theorems
and lead to poor mixing, are shown. Since the mathematical theory applies as
the number of iterations of the map goes to infinity, we introduce practical
measures of mixing (the percent unmixed and the number of intermaterial
interfaces) that can be computed over given (finite) numbers of iterations. We
find that good mixing can be achieved after a finite number of iterations of a
one-dimensional cutting and shuffling map, even though such a map cannot be
considered chaotic in the usual sense and/or it may not fulfill the conditions
of the ergodic theorems for interval exchange transformations. Specifically,
good shuffling can occur with only six or seven intervals of roughly the same
length, as long as the rearrangement order is an irreducible permutation. This
study has implications for a number of mixing processes in which
discontinuities arise either by construction or due to the underlying physics.Comment: 21 pages, 10 figures, ws-ijbc class; accepted for publication in
International Journal of Bifurcation and Chao
Discrete Dynamical Systems Embedded in Cantor Sets
While the notion of chaos is well established for dynamical systems on
manifolds, it is not so for dynamical systems over discrete spaces with
variables, as binary neural networks and cellular automata. The main difficulty
is the choice of a suitable topology to study the limit . By
embedding the discrete phase space into a Cantor set we provided a natural
setting to define topological entropy and Lyapunov exponents through the
concept of error-profile. We made explicit calculations both numerical and
analytic for well known discrete dynamical models.Comment: 36 pages, 13 figures: minor text amendments in places, time running
top to bottom in figures, to appear in J. Math. Phy
Nambu-Hamiltonian flows associated with discrete maps
For a differentiable map that has
an inverse, we show that there exists a Nambu-Hamiltonian flow in which one of
the initial value, say , of the map plays the role of time variable while
the others remain fixed. We present various examples which exhibit the map-flow
correspondence.Comment: 19 page
A repurposing strategy for Hsp90 inhibitors demonstrates their potency against filarial nematodes
Novel drugs are required for the elimination of infections caused by filarial worms, as most commonly used drugs largely target the microfilariae or first stage larvae of these infections. Previous studies, conducted in vitro, have shown that inhibition of Hsp90 kills adult Brugia pahangi. As numerous small molecule inhibitors of Hsp90 have been developed for use in cancer chemotherapy, we tested the activity of several novel Hsp90 inhibitors in a fluorescence polarization assay and against microfilariae and adult worms of Brugia in vitro. The results from all three assays correlated reasonably well and one particular compound, NVP-AUY922, was shown to be particularly active, inhibiting Mf output from female worms at concentrations as low as 5.0 nanomolar after 6 days exposure to drug. NVP-AUY922 was also active on adult worms after a short 24 h exposure to drug. Based on these in vitro data, NVP-AUY922 was tested in vivo in a mouse model and was shown to significantly reduce the recovery of both adult worms and microfilariae. These studies provide proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties
Renormalization Group Functional Equations
Functional conjugation methods are used to analyze the global structure of
various renormalization group trajectories, and to gain insight into the
interplay between continuous and discrete rescaling. With minimal assumptions,
the methods produce continuous flows from step-scaling {\sigma} functions, and
lead to exact functional relations for the local flow {\beta} functions, whose
solutions may have novel, exotic features, including multiple branches. As a
result, fixed points of {\sigma} are sometimes not true fixed points under
continuous changes in scale, and zeroes of {\beta} do not necessarily signal
fixed points of the flow, but instead may only indicate turning points of the
trajectories.Comment: A physical model with a limit cycle added as section IV, along with
reference
Extension of Lorenz Unpredictability
It is found that Lorenz systems can be unidirectionally coupled such that the
chaos expands from the drive system. This is true if the response system is not
chaotic, but admits a global attractor, an equilibrium or a cycle. The
extension of sensitivity and period-doubling cascade are theoretically proved,
and the appearance of cyclic chaos as well as intermittency in interconnected
Lorenz systems are demonstrated. A possible connection of our results with the
global weather unpredictability is provided.Comment: 32 pages, 13 figure
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