Super-rough phase of the random-phase sine-Gordon model: Two-loop results

We consider the two-dimensional random-phase sine-Gordon and study the vicinity of its glass transition temperature $T_c$, in an expansion in small $\tau=(T_c-T)/T_c$, where $T$ denotes the temperature. We derive renormalization group equations in cubic order in the anharmonicity, and show that they contain two universal invariants. Using them we obtain that the correlation function in the super-rough phase for temperature $T<T_c$ behaves at large distances as $\bar{} = \mathcal{A}\ln^2(|x|/a) + \mathcal{O}[\ln(|x|/a)]$, where the amplitude $\mathcal{A}$ is a universal function of temperature $\mathcal{A}=2\tau^2-2\tau^3+\mathcal{O}(\tau^4)$. This result differs at two-loop order, i.e., $\mathcal{O}(\tau^3)$, from the prediction based on results from the "nearly conformal" field theory of a related fermion model. We also obtain the correction-to-scaling exponent.Comment: 34 page

Generalizing the O(N)-field theory to N-colored manifolds of arbitrary internal dimension D

We introduce a geometric generalization of the O(N)-field theory that describes N-colored membranes with arbitrary dimension D. As the O(N)-model reduces in the limit N->0 to self-avoiding polymers, the N-colored manifold model leads to self-avoiding tethered membranes. In the other limit, for inner dimension D->1, the manifold model reduces to the O(N)-field theory. We analyze the scaling properties of the model at criticality by a one-loop perturbative renormalization group analysis around an upper critical line. The freedom to optimize with respect to the expansion point on this line allows us to obtain the exponent \nu of standard field theory to much better precision that the usual 1-loop calculations. Some other field theoretical techniques, such as the large N limit and Hartree approximation, can also be applied to this model. By comparison of low and high temperature expansions, we arrive at a conjecture for the nature of droplets dominating the 3d-Ising model at criticality, which is satisfied by our numerical results. We can also construct an appropriate generalization that describes cubic anisotropy, by adding an interaction between manifolds of the same color. The two parameter space includes a variety of new phases and fixed points, some with Ising criticality, enabling us to extract a remarkably precise value of 0.6315 for the exponent \nu in d=3. A particular limit of the model with cubic anisotropy corresponds to the random bond Ising problem; unlike the field theory formulation, we find a fixed point describing this system at 1-loop order.Comment: 57 pages latex, 26 figures included in the tex

Quality of out-of-hospital palliative emergency care depends on the expertise of the emergency medical team—a prospective multi-centre analysis

The number of palliative care patients who live at home and have non-curable life-threatening diseases is increasing. This is largely a result of modern palliative care techniques (e.g. specialised out-of-hospital palliative medical care services), changes in healthcare policy and the availability of home care services. Accordingly, pre-hospital emergency physicians today are more likely to be involved in out-of-hospital emergency treatment of palliative care patients with advanced disease. In a prospective multi-centre study, we analysed all palliative emergency care calls during a 24-month period across four emergency services in Germany. Participating pre-hospital emergency physicians were rated according to their expertise in emergency and palliative care as follows-group 1: pre-hospital emergency physicians with high experience in emergency and palliative medical care, group 2: pre-hospital emergency physicians with high experience in emergency medical care but less experience in palliative medical care and group 3: pre-hospital emergency physicians with low experience in palliative and emergency medical care. During the period of interest, the centres received 361 emergency calls requiring a response to palliative care patients (2.8% of all 12,996 emergency calls). Ten percent of all patients were treated by group 1; 42% were treated by group 2 and 47% were treated by group 3. There was a statistically significant difference in the treatment of palliative care patients (e.g. transfer to hospital, symptom control, end-of-life decision) as a result of the level of expertise of the investigated pre-hospital emergency physicians (p < 0.01). In Germany, out-of-hospital emergency medical treatment of palliative care patients depends on the expertise in palliative medical care of the pre-hospital emergency physicians who respond to the call. In our investigation, best out-of-hospital palliative medical care was given by pre-hospital emergency physicians who had significant expertise in palliative and emergency medical care. Our results suggest that it may be necessary to take the core principles of palliative care into consideration when conducting out-of-hospital emergency medical treatment of palliative care patients

X chromosome dosage of histone demethylase KDM5C determines sex differences in adiposity

Males and females differ in body composition and fat distribution. Using a mouse model that segregates gonadal sex (ovaries and testes) from chromosomal sex (XX and XY), we showed that XX chromosome complement in combination with a high-fat diet led to enhanced weight gain in the presence of male or female gonads. We identified the genomic dosage of Kdm5c, an X chromosome gene that escapes X chromosome inactivation, as a determinant of the X chromosome effect on adiposity. Modulating Kdm5c gene dosage in XX female mice to levels that are normally present in males resulted in reduced body weight, fat content, and food intake to a degree similar to that seen with altering the entire X chromosome dosage. In cultured preadipocytes, the levels of KDM5C histone demethylase influenced chromatin accessibility (ATAC-Seq), gene expression (RNA-Seq), and adipocyte differentiation. Both in vitro and in vivo, Kdm5c dosage influenced gene expression involved in extracellular matrix remodeling, which is critical for adipocyte differentiation and adipose tissue expansion. In humans, adipose tissue KDM5C mRNA levels and KDM5C genetic variants were associated with body mass. These studies demonstrate that the sex-dependent dosage of Kdm5c contributes to male/female differences in adipocyte biology and highlight X-escape genes as a critical component of female physiology

Viscous regularization and r-adaptive remeshing for finite element analysis of lipid membrane mechanics

As two-dimensional fluid shells, lipid bilayer membranes resist bending and stretching but are unable to sustain shear stresses. This property gives membranes the ability to adopt dramatic shape changes. In this paper, a finite element model is developed to study static equilibrium mechanics of membranes. In particular, a viscous regularization method is proposed to stabilize tangential mesh deformations and improve the convergence rate of nonlinear solvers. The Augmented Lagrangian method is used to enforce global constraints on area and volume during membrane deformations. As a validation of the method, equilibrium shapes for a shape-phase diagram of lipid bilayer vesicle are calculated. These numerical techniques are also shown to be useful for simulations of three-dimensional large-deformation problems: the formation of tethers (long tube-like exetensions); and Ginzburg-Landau phase separation of a two-lipid-component vesicle. To deal with the large mesh distortions of the two-phase model, modification of vicous regularization is explored to achieve r-adaptive mesh optimization

Renormalization group and nonequilibrium action in stochastic field theory

We investigate the renormalization group approach to nonequilibrium field theory. We show that it is possible to derive nontrivial renormalization group flow from iterative coarse graining of a closed-time-path action. This renormalization group is different from the usual in quantum field theory textbooks, in that it describes nontrivial noise and dissipation. We work out a specific example where the variation of the closed-time-path action leads to the so-called Kardar-Parisi-Zhang equation, and show that the renormalization group obtained by coarse graining this action, agrees with the dynamical renormalization group derived by directly coarse graining the equations of motion.Comment: 33 pages, 3 figures included in the text. Revised; one reference adde

E1 transitions between states with n = 1 to 6 in helium-like carbon, nitrogen, oxygen, neon, silicon, and argon

Wavelengths and transition rates are given for E1 transitions between singlet S, P, D, and F states, between triplet S, P, and D states, and between triplet P and singlet S states in ions of astrophysical interest: helium-like carbon, nitrogen, oxygen, neon, silicon, and argon. All possible E1 transitions between states with J < 4 and n < 7 are considered. Energy levels and wave functions used in calculations of the transition rates are obtained from relativistic configuration-interaction calculations that include both Coulomb and Breit interactions.Comment: submitted to Astrophysical Journa

Disorder Induced Phase Transition in a Random Quantum Antiferromagnet

A two-dimensional Heisenberg model with random antiferromagnetic nearest-neighbor exchange is studied using quantum Monte Carlo techniques. As the strength of the randomness is increased, the system undergoes a transition from an antiferromagnetically ordered ground state to a gapless disordered state. The finite-size scaling of the staggered structure factor and susceptibility is consistent with a dynamic exponent $z = 2$.Comment: Revtex 3.0, 10 pages + 5 postscript figures available upon request, UCSBTH-94-1

BET protein inhibition shows efficacy against JAK2V617F-driven neoplasms.

Small molecule inhibition of the BET family of proteins, which bind acetylated lysines within histones, has been shown to have a marked therapeutic benefit in pre-clinical models of mixed lineage leukemia (MLL) fusion protein-driven leukemias. Here, we report that I-BET151, a highly specific BET family bromodomain inhibitor, leads to growth inhibition in a human erythroleukemic (HEL) cell line as well as in erythroid precursors isolated from polycythemia vera patients. One of the genes most highly downregulated by I-BET151 was LMO2, an important oncogenic regulator of hematopoietic stem cell development and erythropoiesis. We previously reported that LMO2 transcription is dependent upon Janus kinase 2 (JAK2) kinase activity in HEL cells. Here, we show that the transcriptional changes induced by a JAK2 inhibitor (TG101209) and I-BET151 in HEL cells are significantly over-lapping, suggesting a common pathway of action. We generated JAK2 inhibitor resistant HEL cells and showed that these retain sensitivity to I-BET151. These data highlight I-BET151 as a potential alternative treatment against myeloproliferative neoplasms driven by constitutively active JAK2 kinase.The Kouzarides laboratory was supported by Cancer Research UK, Leukaemia and Lymphoma Research, GlaxoSmithKline and BBSRC. The Green laboratory was supported by Cancer Research UK and Leukaemia and Lymphoma Research, UK. The Gottgens laboratory was supported by Cancer Research UK and Leukaemia and Lymphoma Research, UK. The Huntly laboratory was supported by Cancer Research UK and Leukaemia and Lymphoma Research, UK. M. A Dawson, E Cannizzaro and M. Wiese are funded by the Wellcome Trust Beit Fellowship.This is the accepted manuscript version of the article. The final version is available from http://www.nature.com/leu/journal/v28/n1/full/leu2013234a.html

Targeting nuclear transporters in cancer: Diagnostic, prognostic and therapeutic potential

The Karyopherin superfamily is a major class of soluble transport receptors consisting of both import and export proteins. The trafficking of proteins involved in transcription, cell signalling and cell cycle regulation among other functions across the nuclear membrane is essential for normal cellular functioning. However, in cancer cells, the altered expression or localization of nuclear transporters as well as the disruption of endogenous nuclear transport inhibitors are some ways in which the Karyopherin proteins are dysregulated. The value of nuclear transporters in the diagnosis, prognosis and treatment of cancer is currently being elucidated with recent studies highlighting their potential as biomarkers and therapeutic targets