Breakdown of Strong-Coupling Perturbation Theory in Doped Mott Insulators

We show that doped Mott insulators, such as the copper-oxide superconductors, are asymptotically slaved in that the quasiparticle weight, $Z$, near half-filling depends critically on the existence of the high energy scale set by the upper Hubbard band. In particular, near half filling, the following dichotomy arises: $Z\ne 0$ when the high energy scale is integrated out but Z=0 in the thermodynamic limit when it is retained. Slavery to the high energy scale arises from quantum interference between electronic excitations across the Mott gap. Broad spectral features seen in photoemission in the normal state of the cuprates are argued to arise from high energy slavery.Comment: Published versio

Potential of ileal bile acid transporter inhibition as a therapeutic target in Alagille syndrome and progressive familial intrahepatic cholestasis

Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC) are rare, inherited cholestatic liver disorders that manifest in infants and children and are associated with impaired bile flow (ie cholestasis), pruritus and potentially fatal liver disease. There are no effective or approved pharmacologic treatments for these diseases (standard medical treatments are supportive only), and new, noninvasive options would be valuable. Typically, bile acids undergo biliary secretion and intestinal reabsorption (ie enterohepatic circulation). However, in these diseases, disrupted secretion of bile acids leads to their accumulation in the liver, which is thought to underlie pruritus and liver-damaging inflammation. One approach to reducing pathologic bile acid accumulation in the body is surgical biliary diversion, which interrupts the enterohepatic circulation (eg by diverting bile acids to an external stoma). These procedures can normalize serum bile acids, reduce pruritus and liver injury and improve quality of life. A novel, nonsurgical approach to interrupting the enterohepatic circulation is inhibition of the ileal bile acid transporter (IBAT), a key molecule in the enterohepatic circulation that reabsorbs bile acids from the intestine. IBAT inhibition has been shown to reduce serum bile acids and pruritus in trials of paediatric cholestatic liver diseases. This review explores the rationale of inhibition of the IBAT as a therapeutic target, describes IBAT inhibitors in development and summarizes the current data on interrupting the enterohepatic circulation as treatment for cholestatic liver diseases including ALGS and PFIC

Everolimus Exposure as a Predictor of Toxicity in Renal Cell Cancer Patients in the Adjuvant Setting: Results of a Pharmacokinetic Analysis for SWOG S0931 (EVEREST), a Phase III Study (NCT01120249).

BackgroundS0931 is assessing recurrence-free survival in renal cell carcinoma (RCC) patients randomized to receive everolimus (EVE) versus placebo for one year following nephrectomy. Due to a higher than expected dropout rate, we assessed EVE trough levels in the adjuvant setting to evaluate the relationship between EVE exposure and probability of toxicity.MethodsPatients received 10 mg daily EVE for nine 6-week cycles. Pre-dose whole blood samples were collected pre-cycle 2 and pre-cycle 3 and analyzed for EVE. Patients with pre-cycle 2 and/or pre-cycle 3 EVE results were used in the analysis. Patients were segregated into quartiles (Q) based on EVE levels and logistic regression was used to model the most common adverse event outcomes using EVE trough as a predictor. Hazard and odds ratios were adjusted for age, BMI and performance status.ResultsA total of 467 patients were included in this analysis. Quartiles normalized to an EVE dose of 10 mg/day were < 9.0, 9.0-12.9, 12.9-22.8, and > 22.8 ng/mL, respectively. EVE trough levels increased with increasing age (p < 0.001). Furthermore, EVE trough levels were higher in men than women (19.4 versus 15.4 ng/mL, p = 0.01). Risk of grade 2 + triglycerides was increased in Q2 and Q3 vs Q1 (OR = 2.08; p = 0.02 and OR = 2.63; p = 0.002). Risk of grade 2 + rash was increased in Q2 and Q4 vs Q1 (OR = 2.99; p = 0.01 and OR = 2.90; p = 0.02). There was also an increased risk of any grade 3 + tox in Q2 vs Q1 (OR = 1.71; p = 0.05).ConclusionsWe identified significant gender and age-related differences in EVE trough levels in patients receiving adjuvant treatment for RCC. Furthermore, our analysis identified significant associations between EVE exposure and probability of toxicity

Constitutional Analogies in the International Legal System

This Article explores issues at the frontier of international law and constitutional law. It considers five key structural and systemic challenges that the international legal system now faces: (1) decentralization and disaggregation; (2) normative and institutional hierarchies; (3) compliance and enforcement; (4) exit and escape; and (5) democracy and legitimacy. Each of these issues raises questions of governance, institutional design, and allocation of authority paralleling the questions that domestic legal systems have answered in constitutional terms. For each of these issues, I survey the international legal landscape and consider the salience of potential analogies to domestic constitutions, drawing upon and extending the writings of international legal scholars and international relations theorists. I also offer some preliminary thoughts about why some treaties and institutions, but not others, more readily lend themselves to analysis in constitutional terms. And I distinguish those legal and political issues that may generate useful insights for scholars studying the growing intersections of international and constitutional law from other areas that may be more resistant to constitutional analogies

Charge Fluctuations on Membrane Surfaces in Water

We generalize the predictions for attractions between over-all neutral surfaces induced by charge fluctuations/correlations to non-uniform systems that include dielectric discontinuities, as is the case for mixed charged lipid membranes in an aqueous solution. We show that the induced interactions depend in a non-trivial way on the dielectric constants of membrane and water and show different scaling with distance depending on these properties. The generality of the calculations also allows us to predict under which dielectric conditions the interaction will change sign and become repulsive

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of prostate carcinoma.

Prostate cancer is the most commonly diagnosed malignancy and second leading cause of cancer death among men in the United States. In recent years, several new agents, including cancer immunotherapies, have been approved or are currently being investigated in late-stage clinical trials for the management of advanced prostate cancer. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel, including physicians, nurses, and patient advocates, to develop consensus recommendations for the clinical application of immunotherapy for prostate cancer patients. To do so, a systematic literature search was performed to identify high-impact papers from 2006 until 2014 and was further supplemented with literature provided by the panel. Results from the consensus panel voting and discussion as well as the literature review were used to rate supporting evidence and generate recommendations for the use of immunotherapy in prostate cancer patients. Sipuleucel-T, an autologous dendritic cell vaccine, is the first and currently only immunotherapeutic agent approved for the clinical management of metastatic castrate resistant prostate cancer (mCRPC). The consensus panel utilized this model to discuss immunotherapy in the treatment of prostate cancer, issues related to patient selection, monitoring of patients during and post treatment, and sequence/combination with other anti-cancer treatments. Potential immunotherapies emerging from late-stage clinical trials are also discussed. As immunotherapy evolves as a therapeutic option for the treatment of prostate cancer, these recommendations will be updated accordingly

CHANG-ES XI: Circular Polarization in the Cores of Nearby Galaxies

We detect 5 galaxies in the CHANG-ES (Continuum Halos in Nearby Galaxies -- an EVLA Survey) sample that show circular polarization (CP) at L-band in our high resolution data sets. Two of the galaxies (NGC~4388 and NGC~4845) show strong Stokes $V/I\,\equiv\,m_C\,\sim\,2$\%, two (NGC~660 and NGC~3628) have values of $m_C\sim \,0.3$\%, and NGC~3079 is a marginal detection at $m_C\sim \,0.2$\%. The two strongest $m_C$ galaxies also have the most luminous X-ray cores and the strongest internal absorption in X-rays. We have expanded on our previous Faraday conversion interpretation and analysis and provide analytical expressions for the expected $V$ signal for a general case in which the cosmic ray electron energy spectral index can take on any value. We provide examples as to how such expressions could be used to estimate magnetic field strengths and the lower energy cutoff for CR electrons. Four out of our detections are {\it resolved}, showing unique structures, including a {\it jet} in NGC~4388 and a CP `conversion disk' in NGC~4845. The conversion disk is inclined to the galactic disk but is perpendicular to a possible outflow direction. Such CP structures have never before been seen in any galaxy to our knowledge. None of the galaxy cores show linear polarization at L-band. Thus CP may provide a unique probe of physical conditions deep into radio AGNs.Comment: 30 pages, 4 figures, accepted to MNRA

CHANG-ES IV: Radio continuum emission of 35 edge-on galaxies observed with the Karl G. Jansky Very Large Array in D-configuration, Data Release 1

We present the first part of the observations made for the Continuum Halos in Nearby Galaxies, an EVLA Survey (CHANG-ES) project. The aim of the CHANG-ES project is to study and characterize the nature of radio halos, their prevalence as well as their magnetic fields, and the cosmic rays illuminating these fields. This paper reports observations with the compact D configuration of the Karl G. Jansky Very Large Array (VLA) for the sample of 35 nearby edge-on galaxies of CHANG-ES. With the new wide bandwidth capabilities of the VLA, an unprecedented sensitivity was achieved for all polarization products. The beam resolution is an average of 9.6" and 36" with noise levels reaching approximately 6 and 30 microJy per beam for C- and L-bands, respectively (robust weighting). We present intensity maps in these two frequency bands (C and L), with different weightings, as well as spectral index maps, polarization maps, and new measurements of star formation rates (SFRs). The data products described herein are available to the public in the CHANG-ES data release available at www.queensu.ca/changes. We also present evidence of a trend among galaxies with larger halos having higher SFR surface density, and we show, for the first time, a radio continuum image of the median galaxy, taking advantage of the collective signal-to-noise ratio of 30 of our galaxies. This image shows clearly that a typical spiral galaxy is surrounded by a halo of magnetic fields and cosmic rays.Comment: 70 pages, of which 35 pages present the data of each galax

Percolating Reaction-Diffusion Waves (PERWAVES) — Sounding Rocket Combustion Experiments

Percolating reaction–diffusion waves in disordered random media are encountered in many branches of modern science, ranging from physics and biology to material science and combustion. Most disordered reaction–diffusion systems, however, have complex morphologies and reaction kinetics that complicate the study of the dynamics. Flames in suspensions of heterogeneously reacting metal-fuel particles is a rare example of a reaction–diffusion wave with a simple structure formed by point-like heat sources having well-defined ignition temperature thresholds and combustion times. Particle sedimentation and natural convection can be suppressed in the free-fall conditions of sounding rocket experiments, enabling the properties of percolating flames in suspensions to be observed, studied, and compared with emerging theoretical models. The current paper describes the design of the European Space Agency PERWAVES microgravity combustion apparatus, built by the Airbus Defense and Space team from Bremen in collaboration with the scientific research teams from McGill University and the Technical University of Eindhoven, and discusses the results of two sounding-rocket flight experiments. The apparatus allows multiple flame experiments in quartz glass tubes filled with uniform suspensions of 25-micron iron particles in oxygen/xenon gas mixtures. The experiments performed during the MAXUS-9 (April 2017) and TEXUS-56 (November 2019) sounding rocket flights have confirmed flame propagation in the discrete mode, which is a pre-requisite for percolating-flame behavior, and have allowed observation of the flame structure in the vicinity of the propagation threshold