Maximal Entanglement, Collective Coordinates and Tracking the King

Maximal entangled states (MES) provide a basis to two d-dimensional particles Hilbert space, d=prime $\ne 2$. The MES forming this basis are product states in the collective, center of mass and relative, coordinates. These states are associated (underpinned) with lines of finite geometry whose constituent points are associated with product states carrying Mutual Unbiased Bases (MUB) labels. This representation is shown to be convenient for the study of the Mean King Problem and a variant thereof, termed Tracking the King which proves to be a novel quantum communication channel. The main topics, notions used are reviewed in an attempt to have the paper self contained.Comment: 8. arXiv admin note: substantial text overlap with arXiv:1206.3884, arXiv:1206.035

The properties of the Malin 1 galaxy giant disk: A panchromatic view from the NGVS and GUViCS surveys

Low surface brightness galaxies (LSBGs) represent a significant percentage of local galaxies but their formation and evolution remain elusive. They may hold crucial information for our understanding of many key issues (i.e., census of baryonic and dark matter, star formation in the low density regime, mass function). The most massive examples - the so called giant LSBGs - can be as massive as the Milky Way, but with this mass being distributed in a much larger disk. Malin 1 is an iconic giant LSBG, perhaps the largest disk galaxy known. We attempt to bring new insights on its structure and evolution on the basis of new images covering a wide range in wavelength. We have computed surface brightness profiles (and average surface brightnesses in 16 regions of interest), in six photometric bands (FUV, NUV, u, g, i, z). We compared these data to various models, testing a variety of assumptions concerning the formation and evolution of Malin 1. We find that the surface brightness and color profiles can be reproduced by a long and quiet star-formation history due to the low surface density; no significant event, such as a collision, is necessary. Such quiet star formation across the giant disk is obtained in a disk model calibrated for the Milky Way, but with an angular momentum approximately 20 times larger. Signs of small variations of the star-formation history are indicated by the diversity of ages found when different regions within the galaxy are intercompared.For the first time, panchromatic images of Malin 1 are used to constrain the stellar populations and the history of this iconic example among giant LSBGs. Based on our model, the extreme disk of Malin 1 is found to have a long history of relatively low star formation (about 2 Msun/yr). Our model allows us to make predictions on its stellar mass and metallicity.Comment: Accepted in Astronomy and Astrophysic

Commercializing Biomedical Research Through Securitization Techniques

Biomedical innovation has become riskier, more expensive and more difficult to finance with traditional sources such as private and public equity. Here we propose a financial structure in which a large number of biomedical programs at various stages of development are funded by a single entity to substantially reduce the portfolio's risk. The portfolio entity can finance its activities by issuing debt, a critical advantage because a much larger pool of capital is available for investment in debt versus equity. By employing financial engineering techniques such as securitization, it can raise even greater amounts of more-patient capital. In a simulation using historical data for new molecular entities in oncology from 1990 to 2011, we find that megafunds of $5–15 billion may yield average investment returns of 8.9–11.4% for equity holders and 5–8% for 'research-backed obligation' holders, which are lower than typical venture-capital hurdle rates but attractive to pension funds, insurance companies and other large institutional investors

Regularized fitted Q-iteration: application to planning

We consider planning in a Markovian decision problem, i.e., the problem of finding a good policy given access to a generative model of the environment. We propose to use fitted Q-iteration with penalized (or regularized) least-squares regression as the regression subroutine to address the problem of controlling model-complexity. The algorithm is presented in detail for the case when the function space is a reproducing kernel Hilbert space underlying a user-chosen kernel function. We derive bounds on the quality of the solution and argue that data-dependent penalties can lead to almost optimal performance. A simple example is used to illustrate the benefits of using a penalized procedure

Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease

OBJECTIVE: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines. STUDY DESIGN: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention. RESULTS: There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications. CONCLUSIONS: More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management

Drug Repurposing: Far Beyond New Targets for Old Drugs

Repurposing drugs requires finding novel therapeutic indications compared to the ones for which they were already approved. This is an increasingly utilized strategy for finding novel medicines, one that capitalizes on previous investments while derisking clinical activities. This approach is of interest primarily because we continue to face significant gaps in the drug–target interactions matrix and to accumulate safety and efficacy data during clinical studies. Collecting and making publicly available as much data as possible on the target profile of drugs offer opportunities for drug repurposing, but may limit the commercial applications by patent applications. Certain clinical applications may be more feasible for repurposing than others because of marked differences in side effect tolerance. Other factors that ought to be considered when assessing drug repurposing opportunities include relevance to the disease in question and the intellectual property landscape. These activities go far beyond the identification of new targets for old drugs

Metaphors in Nanomedicine: The Case of Targeted Drug Delivery

International audienceThe promises of nanotechnology have been framed by a variety of metaphors, that not only channel the attention of the public, orient the questions asked by researchers, and convey epistemic choices closely linked to ethical preferences. In particular, the image of the 'therapeutic missile' commonly used to present targeted drug delivery devices emphasizes precision, control, surveillance and efficiency. Such values are highly praised in the current context of crisis of pharmaceutical innovation where military metaphors foster a general mobilization of resources from multiple fields of cutting-edge research. The missile metaphor, reminiscent of Paul Ehrlich's 'magic bullet', has framed the problem in simple terms: how to deliver the right dose in the right place at the right moment? Chemists, physicists and engineers who design multi-functional devices operating in vitro can think in such terms, as long as the devices are not actually operating through the messy environment of the body. A close look at what has been done and what remains to be done suggests that the metaphor of the "therapeutic missile" is neither sufficient, nor even necessary. Recent developments in nanomedicine suggest that therapeutic efficacy cannot be obtained without negotiating with the biological milieu and taking advantage of what it affords. An 'oïkological' approach seems more appropriate, more heuristic and more promising than the popular missile. It is based on the view of organism as an oikos that has to be carefully managed. The dispositions of nanocapsules have to be coupled with the affordances of the environment. As it requires dealing with nanoparticles as relational entities (defined by their potential for interactions) rather than as stable substances (defined by intrinsic properties) this metaphor eventually might well change research priorities in nanotechnology in general

Learning near-optimal policies with Bellman-residual minimization based fitted policy iteration and a single sample path

We consider the problem of finding a near-optimal policy in continuous space, discounted Markovian Decision Problems given the trajectory of some behaviour policy. We study the policy iteration algorithm where in successive iterations the action-value functions of the intermediate policies are obtained by picking a function from some fixed function set (chosen by the user) that minimizes an unbiased finite-sample approximation to a novel loss function that upper-bounds the unmodified Bellman-residual criterion. The main result is a finite-sample, high-probability bound on the performance of the resulting policy that depends on the mixing rate of the trajectory, the capacity of the function set as measured by a novel capacity concept that we call the VC-crossing dimension, the approximation power of the function set and the discounted-average concentrability of the future-state distribution. To the best of our knowledge this is the first theoretical reinforcement learning result for off-policy control learning over continuous state-spaces using a single trajectory

Shaping a screening file for maximal lead discovery efficiency and effectiveness: elimination of molecular redundancy

High Throughput Screening (HTS) is a successful strategy for finding hits and leads that have the opportunity to be converted into drugs. In this paper we highlight novel computational methods used to select compounds to build a new screening file at Pfizer and the analytical methods we used to assess their quality. We also introduce the novel concept of molecular redundancy to help decide on the density of compounds required in any region of chemical space in order to be confident of running successful HTS campaigns

In Children with Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis is Associated with Advanced Fibrosis

Background & Aims Focal zone 1 steatosis, although rare in adults with nonalcoholic fatty liver disease (NAFLD), does occur in children with NAFLD. We investigated whether focal zone 1 steatosis and focal zone 3 steatosis are distinct subphenotypes of pediatric NAFLD. We aimed to determine associations between the zonality of steatosis and demographic, clinical, and histologic features in children with NAFLD. Methods We performed a cross-sectional study of baseline data from 813 children (age <18 years; mean age, 12.8 ± 2.7 years). The subjects had biopsy-proven NAFLD and were enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network. Liver histology was reviewed using the Nonalcoholic Steatohepatitis Clinical Research Network scoring system. Results Zone 1 steatosis was present in 18% of children with NAFLD (n = 146) and zone 3 steatosis was present in 32% (n = 244). Children with zone 1 steatosis were significantly younger (10 vs 14 years; P < .001) and a significantly higher proportion had any fibrosis (81% vs 51%; P < .001) or advanced fibrosis (13% vs 5%; P < .001) compared with children with zone 3 steatosis. In contrast, children with zone 3 steatosis were significantly more likely to have steatohepatitis (30% vs 6% in children with zone 1 steatosis; P < .001). Conclusions Children with zone 1 or zone 3 distribution of steatosis have an important subphenotype of pediatric NAFLD. Children with zone 1 steatosis are more likely to have advanced fibrosis and children with zone 3 steatosis are more likely to have steatohepatitis. To achieve a comprehensive understanding of pediatric NAFLD, studies of pathophysiology, natural history, and response to treatment should account for the zonality of steatosis