Vacuum polarization for lukewarm black holes

We compute the renormalized expectation value of the square of a quantum scalar field on a Reissner-Nordström–de Sitter black hole in which the temperatures of the event and cosmological horizons are equal (“lukewarm” black hole). Our numerical calculations for a thermal state at the same temperature as the two horizons indicate that this renormalized expectation value is regular on both the event and cosmological horizons. We are able to show analytically, using an approximation for the field modes near the horizons, that this is indeed the case

Polynomial Time Algorithms for Branching Markov Decision Processes and Probabilistic Min(Max) Polynomial Bellman Equations

We show that one can approximate the least fixed point solution for a multivariate system of monotone probabilistic max(min) polynomial equations, referred to as maxPPSs (and minPPSs, respectively), in time polynomial in both the encoding size of the system of equations and in log(1/epsilon), where epsilon > 0 is the desired additive error bound of the solution. (The model of computation is the standard Turing machine model.) We establish this result using a generalization of Newton's method which applies to maxPPSs and minPPSs, even though the underlying functions are only piecewise-differentiable. This generalizes our recent work which provided a P-time algorithm for purely probabilistic PPSs. These equations form the Bellman optimality equations for several important classes of infinite-state Markov Decision Processes (MDPs). Thus, as a corollary, we obtain the first polynomial time algorithms for computing to within arbitrary desired precision the optimal value vector for several classes of infinite-state MDPs which arise as extensions of classic, and heavily studied, purely stochastic processes. These include both the problem of maximizing and mininizing the termination (extinction) probability of multi-type branching MDPs, stochastic context-free MDPs, and 1-exit Recursive MDPs. Furthermore, we also show that we can compute in P-time an epsilon-optimal policy for both maximizing and minimizing branching, context-free, and 1-exit-Recursive MDPs, for any given desired epsilon > 0. This is despite the fact that actually computing optimal strategies is Sqrt-Sum-hard and PosSLP-hard in this setting. We also derive, as an easy consequence of these results, an FNP upper bound on the complexity of computing the value (within arbitrary desired precision) of branching simple stochastic games (BSSGs)

Hepatic heparan sulfate is a master regulator of hepcidin expression and iron homeostasis in human hepatocytes and mice.

Hepcidin is a liver-derived peptide hormone that controls systemic iron homeostasis. Its expression is regulated by the bone morphogenetic protein 6 (BMP6)/SMAD1/5/8 pathway and by the proinflammatory cytokine interleukin 6 (IL6). Proteoglycans that function as receptors of these signaling proteins in the liver are commonly decorated by heparan sulfate, but the potential role of hepatic heparan sulfate in hepcidin expression and iron homeostasis is unclear. Here, we show that modulation of hepatic heparan sulfate significantly alters hepcidin expression and iron metabolism both in vitro and in vivo Specifically, enzymatic removal of heparan sulfate from primary human hepatocytes, CRISPR/Cas9 manipulation of heparan sulfate biosynthesis in human hepatoma cells, or pharmacological manipulation of heparan sulfate-protein interactions using sodium chlorate or surfen dramatically reduced baseline and BMP6/SMAD1/5/8-dependent hepcidin expression. Moreover inactivation of the heparan sulfate biosynthetic gene N-deacetylase and N-sulfotransferase 1 (Ndst1) in murine hepatocytes (Ndst1 f/f AlbCre +) reduced hepatic hepcidin expression and caused a redistribution of systemic iron, leading to iron accumulation in the liver and serum of mice. Manipulation of heparan sulfate had a similar effect on IL6-dependent hepcidin expression in vitro and suppressed IL6-mediated iron redistribution induced by lipopolysaccharide in vivo These results provide compelling evidence that hepatocyte heparan sulfate plays a key role in regulating hepcidin expression and iron homeostasis in mice and in human hepatocytes

Kinks Dynamics in One-Dimensional Coupled Map Lattices

We examine the problem of the dynamics of interfaces in a one-dimensional space-time discrete dynamical system. Two different regimes are studied : the non-propagating and the propagating one. In the first case, after proving the existence of such solutions, we show how they can be described using Taylor expansions. The second situation deals with the assumption of a travelling wave to follow the kink propagation. Then a comparison with the corresponding continuous model is proposed. We find that these methods are useful in simple dynamical situations but their application to complex dynamical behaviour is not yet understood.Comment: 17pages, LaTex,3 fig available on cpt.univ-mrs.fr directory pub/preprints/94/dynamical-systems/94-P.307

In-Vivo Biodistribution and Safety of 99mTc-LLP2A-HYNIC in Canine Non-Hodgkin Lymphoma

Theranostic agents are critical for improving the diagnosis and treatment of non-Hodgkin Lymphoma (NHL). The peptidomimetic LLP2A is a novel peptide receptor radiotherapy candidate for treating NHL that expresses the activated α4β1 integrin. Tumor-bearing dogs are an excellent model of human NHL with similar clinical characteristics, behavior, and compressed clinical course. Canine in vivo imaging studies will provide valuable biodistribution and affinity information that reflects a diverse clinical population of lymphoma. This may also help to determine potential dose-limiting radiotoxicity to organs in human clinical trials. To validate this construct in a naturally occurring model of NHL, we performed in-vivo molecular targeted imaging and biodistribution in 3 normal dogs and 5 NHL bearing dogs. 99mTc-LLP2A-HYNIC-PEG and 99mTc-LLP2A-HYNIC were successfully synthesized and had very good labeling efficiency and radiochemical purity. 99mTc-LLP2A-HYNIC and 99mTc-LLP2A-HYNIC-PEG had biodistribution in keeping with their molecular size, with 99mTc-LLP2A-HYNIC-PEG remaining longer in the circulation, having higher tissue uptake, and having more activity in the liver compared to 99mTc-LLP2A-HYNIC. 99mTc-LLP2A-HYNIC was mainly eliminated through the kidneys with some residual activity. Radioactivity was reduced to near-background levels at 6 hours after injection. In NHL dogs, tumor showed moderately increased activity over background, with tumor activity in B-cell lymphoma dogs decreasing after chemotherapy. This compound is promising in the development of targeted drug-delivery radiopharmaceuticals and may contribute to translational work in people affected by non-Hodgkin lymphoma

Severe Rhabdomyolysis Due To Adipsic Hypernatremia After Craniopharyngioma Surgery.

The association of diabetes insipidus and adipsia after craniopharyngioma surgery has high morbidity. Hypernatremia can be caused by adipsia and be aggravated by diabetes insipidus. Rhabdomyolysis rarely occurs. This is the first report of a diabetic patient with craniopharyngioma who developed diabetes insipidus and adipsia after surgery, evolving with severe hypernatremia that caused considerable rhabdomyolysis. The importance of the evaluation of muscle integrity when under hypernatremic states is pointed out. Although adipsia may have a simple solution through volunteer water ingestion, serious consequences such as repeated severe hypernatremia episodes and intense rhabdomyolysis with high morbidity could occur, if adipsia is not diagnosed.511175-

The Fulling-Unruh effect in general stationary accelerated frames

We study the generalized Unruh effect for accelerated reference frames that include rotation in addition to acceleration. We focus particularly on the case where the motion is planar, with presence of a static limit in addition to the event horizon. Possible definitions of an accelerated vacuum state are examined and the interpretation of the Minkowski vacuum state as a thermodynamic state is discussed. Such athermodynamic state is shown to depend on two parameters, the acceleration temperature and a drift velocity, which are determined by the acceleration and angular velocity of the accelerated frame. We relate the properties of Minkowski vacuum in the accelerated frame to the excitation spectrum of a detector that is stationary in this frame. The detector can be excited both by absorbing positive energy quanta in the "hot" vacuum state and by emitting negative energy quanta into the "ergosphere" between the horizon and the static limit. The effects are related to similar effects in the gravitational field of a rotating black hole.Comment: Latex, 39 pages, 5 figure

Precision delivery of RAS-inhibiting siRNA to KRAS driven cancer via peptide-based nanoparticles

Over 95% of pancreatic adenocarcinomas (PDACs), as well as a large fraction of other tumor types, such as colorectal adenocarcinoma, are driven by KRAS activation. However, no direct RAS inhibitors exist for cancer therapy. Furthermore, the delivery of therapeutic agents of any kind to PDAC in particular has been hindered by the extensive desmoplasia and resultant drug delivery challenges that accompanies these tumors. Small interfering RNA (siRNA) is a promising modality for anti-neoplastic therapy due to its precision and wide range of potential therapeutic targets. Unfortunately, siRNA therapy is limited by low serum half-life, vulnerability to intracellular digestion, and transient therapeutic effect. We assessed the ability of a peptide based, oligonucleotide condensing, endosomolytic nanoparticle (NP) system to deliver siRNA to KRAS-driven cancers. We show that this peptide-based NP is avidly taken up by cancer cell