Sugawara-type constraints in hyperbolic coset models

In the conjectured correspondence between supergravity and geodesic models on infinite-dimensional hyperbolic coset spaces, and E10/K(E10) in particular, the constraints play a central role. We present a Sugawara-type construction in terms of the E10 Noether charges that extends these constraints infinitely into the hyperbolic algebra, in contrast to the truncated expressions obtained in arXiv:0709.2691 that involved only finitely many generators. Our extended constraints are associated to an infinite set of roots which are all imaginary, and in fact fill the closed past light-cone of the Lorentzian root lattice. The construction makes crucial use of the E10 Weyl group and of the fact that the E10 model contains both D=11 supergravity and D=10 IIB supergravity. Our extended constraints appear to unite in a remarkable manner the different canonical constraints of these two theories. This construction may also shed new light on the issue of `open constraint algebras' in traditional canonical approaches to gravity.Comment: 49 page

Use of clofarabine for acute childhood leukemia

A second-generation of purine nucleoside analogs, starting with clofarabine, has been developed in the course of the search for new therapeutic agents for acute childhood leukemia, especially for refractory or relapsed disease. Clofarabine is a hybrid of fludarabine and cladribine, and has shown to have antileukemic activity in acute lymphoblastic leukemia as well as in myeloid disorders. As the only new antileukemic chemotherapeutic agent to enter clinical use in the last 10 years, clofarabine was approved as an orphan drug with the primary indication of use in pediatric patients. Toxicity has been tolerable in a heavily pretreated patient population, and clofarabine has been demonstrated to be safe, both as a single agent and in combination therapies. Liver dysfunction has been the most frequently observed adverse event, but this is generally reversible. Numerous Phase I and II trials have recently been conducted, and are still ongoing in an effort to find the optimal role for clofarabine in various treatment strategies. Concomitant use of clofarabine, cytarabine, and etoposide was confirmed to be safe and effective in two independent trials. Based on the promising results when used as a salvage regimen, clofarabine is now being investigated for its potential to become part of frontline protocols

Use of clofarabine for acute childhood leukemia.

A second-generation of purine nucleoside analogs, starting with clofarabine, has been developed in the course of the search for new therapeutic agents for acute childhood leukemia, especially for refractory or relapsed disease. Clofarabine is a hybrid of fludarabine and cladribine, and has shown to have antileukemic activity in acute lymphoblastic leukemia as well as in myeloid disorders. As the only new antileukemic chemotherapeutic agent to enter clinical use in the last 10 years, clofarabine was approved as an orphan drug with the primary indication of use in pediatric patients. Toxicity has been tolerable in a heavily pretreated patient population, and clofarabine has been demonstrated to be safe, both as a single agent and in combination therapies. Liver dysfunction has been the most frequently observed adverse event, but this is generally reversible. Numerous Phase I and II trials have recently been conducted, and are still ongoing in an effort to find the optimal role for clofarabine in various treatment strategies. Concomitant use of clofarabine, cytarabine, and etoposide was confirmed to be safe and effective in two independent trials. Based on the promising results when used as a salvage regimen, clofarabine is now being investigated for its potential to become part of frontline protocols

Colourful Poincaré symmetry, gravity and particle actions

We construct a generalisation of the three-dimensional Poincar\'e algebra that also includes a colour symmetry factor. This algebra can be used to define coloured Poincar\'e gravity in three space-time dimensions as well as to study generalisations of massive and massless free particle models. We present various such generalised particle models that differ in which orbits of the coloured Poincar\'e symmetry are described. Our approach can be seen as a stepping stone towards the description of particles interacting with a non-abelian background field or as a starting point for a worldline formulation of an associated quantum field theory

Curvature corrections and Kac-Moody compatibility conditions

We study possible restrictions on the structure of curvature corrections to gravitational theories in the context of their corresponding Kac--Moody algebras, following the initial work on E10 in Class. Quant. Grav. 22 (2005) 2849. We first emphasize that the leading quantum corrections of M-theory can be naturally interpreted in terms of (non-gravity) fundamental weights of E10. We then heuristically explore the extent to which this remark can be generalized to all over-extended algebras by determining which curvature corrections are compatible with their weight structure, and by comparing these curvature terms with known results on the quantum corrections for the corresponding gravitational theories.Comment: 27 page

Eisenstein series for infinite-dimensional U-duality groups

We consider Eisenstein series appearing as coefficients of curvature corrections in the low-energy expansion of type II string theory four-graviton scattering amplitudes. We define these Eisenstein series over all groups in the E_n series of string duality groups, and in particular for the infinite-dimensional Kac-Moody groups E9, E10 and E11. We show that, remarkably, the so-called constant term of Kac-Moody-Eisenstein series contains only a finite number of terms for particular choices of a parameter appearing in the definition of the series. This resonates with the idea that the constant term of the Eisenstein series encodes perturbative string corrections in BPS-protected sectors allowing only a finite number of corrections. We underpin our findings with an extensive discussion of physical degeneration limits in D<3 space-time dimensions.Comment: 69 pages. v2: Added references and small additions, to be published in JHE

E10 and Gauged Maximal Supergravity

We compare the dynamics of maximal three-dimensional gauged supergravity in appropriate truncations with the equations of motion that follow from a one-dimensional E10/K(E10) coset model at the first few levels. The constant embedding tensor, which describes gauge deformations and also constitutes an M-theoretic degree of freedom beyond eleven-dimensional supergravity, arises naturally as an integration constant of the geodesic model. In a detailed analysis, we find complete agreement at the lowest levels. At higher levels there appear mismatches, as in previous studies. We discuss the origin of these mismatches.Comment: 34 pages. v2: added references and typos corrected. Published versio

Role of osmotic and hydrostatic pressures in bacteriophage genome ejection

A critical step in the bacteriophage life cycle is genome ejection into host bacteria. The ejection process for double-stranded DNA phages has been studied thoroughly \textit{in vitro}, where after triggering with the cellular receptor the genome ejects into a buffer. The experimental data have been interpreted in terms of the decrease in free energy of the densely packed DNA associated with genome ejection. Here we detail a simple model of genome ejection in terms of the hydrostatic and osmotic pressures inside the phage, a bacterium, and a buffer solution/culture medium. We argue that the hydrodynamic flow associated with the water movement from the buffer solution into the phage capsid and further drainage into the bacterial cytoplasm, driven by the osmotic gradient between the bacterial cytoplasm and culture medium, provides an alternative mechanism for phage genome ejection \textit{in vivo}; the mechanism is perfectly consistent with phage genome ejection \textit{in vitro}.Comment: 5 pages, 2 figures, references update

K(E9) from K(E10)

We analyse the M-theoretic generalisation of the tangent space structure group after reduction of the D=11 supergravity theory to two space-time dimensions in the context of hidden Kac-Moody symmetries. The action of the resulting infinite-dimensional `R symmetry' group K(E9) on certain unfaithful, finite-dimensional spinor representations inherited from K(E10) is studied. We explain in detail how these representations are related to certain finite codimension ideals within K(E9), which we exhibit explicitly, and how the known, as well as new finite-dimensional `generalised holonomy groups' arise as quotients of K(E9) by these ideals. In terms of the loop algebra realisations of E9 and K(E9) on the fields of maximal supergravity in two space-time dimensions, these quotients are shown to correspond to (generalised) evaluation maps, in agreement with previous results of Nicolai and Samtleben (hep-th/0407055). The outstanding question is now whether the related unfaithful representations of K(E10) can be understood in a similar way.Comment: 35 pages; v2: References added; v3: Author, one reference and two appendices added. Extended results in sections 3.2 and 4.