Equilibrium solutions of the shallow water equations

A statistical method for calculating equilibrium solutions of the shallow water equations, a model of essentially 2-d fluid flow with a free surface, is described. The model contains a competing acoustic turbulent {\it direct} energy cascade, and a 2-d turbulent {\it inverse} energy cascade. It is shown, nonetheless that, just as in the corresponding theory of the inviscid Euler equation, the infinite number of conserved quantities constrain the flow sufficiently to produce nontrivial large-scale vortex structures which are solutions to a set of explicitly derived coupled nonlinear partial differential equations.Comment: 4 pages, no figures. Submitted to Physical Review Letter

Magneto-optical Kerr Effect Studies of Square Artificial Spin Ice

We report a magneto-optical Kerr effect study of the collective magnetic response of artificial square spin ice, a lithographically-defined array of single-domain ferromagnetic islands. We find that the anisotropic inter-island interactions lead to a non-monotonic angular dependence of the array coercive field. Comparisons with micromagnetic simulations indicate that the two perpendicular sublattices exhibit distinct responses to island edge roughness, which clearly influence the magnetization reversal process. Furthermore, such comparisons demonstrate that disorder associated with roughness in the island edges plays a hitherto unrecognized but essential role in the collective behavior of these systems.Comment: Physical Review B, Rapid Communications (in press

The Renormalization Group Improvement of the QCD Static Potentials

We resum the leading ultrasoft logs of the singlet and octet static QCD potentials within potential NRQCD. We then obtain the complete three-loop renormalization group improvement of the singlet QCD static potential. The discrepancies between the perturbative evaluation and the lattice results at short distances are slightly reduced.Comment: 9 pages, LaTeX, 1 figure. Journal version. Minor changes in the tex

Monitoring retinal changes with optical coherence tomography predicts neuronal loss in experimental autoimmune encephalomyelitis.

BACKGROUND:Retinal optical coherence tomography (OCT) is a clinical and research tool in multiple sclerosis, where it has shown significant retinal nerve fiber (RNFL) and ganglion cell (RGC) layer thinning, while postmortem studies have reported RGC loss. Although retinal pathology in experimental autoimmune encephalomyelitis (EAE) has been described, comparative OCT studies among EAE models are scarce. Furthermore, the best practices for the implementation of OCT in the EAE lab, especially with afoveate animals like rodents, remain undefined. We aimed to describe the dynamics of retinal injury in different mouse EAE models and outline the optimal experimental conditions, scan protocols, and analysis methods, comparing these to histology to confirm the pathological underpinnings. METHODS:Using spectral-domain OCT, we analyzed the test-retest and the inter-rater reliability of volume, peripapillary, and combined horizontal and vertical line scans. We then monitored the thickness of the retinal layers in different EAE models: in wild-type (WT) C57Bl/6J mice immunized with myelin oligodendrocyte glycoprotein peptide (MOG35-55) or with bovine myelin basic protein (MBP), in TCR2D2 mice immunized with MOG35-55, and in SJL/J mice immunized with myelin proteolipid lipoprotein (PLP139-151). Strain-matched control mice were sham-immunized. RGC density was counted on retinal flatmounts at the end of each experiment. RESULTS:Volume scans centered on the optic disc showed the best reliability. Retinal changes during EAE were localized in the inner retinal layers (IRLs, the combination of the RNFL and the ganglion cell plus the inner plexiform layers). In WT, MOG35-55 EAE, progressive thinning of IRL started rapidly after EAE onset, with 1/3 of total loss occurring during the initial 2 months. IRL thinning was associated with the degree of RGC loss and the severity of EAE. Sham-immunized SJL/J mice showed progressive IRL atrophy, which was accentuated in PLP-immunized mice. MOG35-55-immunized TCR2D2 mice showed severe EAE and retinal thinning. MBP immunization led to very mild disease without significant retinopathy. CONCLUSIONS:Retinal neuroaxonal damage develops quickly during EAE. Changes in retinal thickness mirror neuronal loss and clinical severity. Monitoring of the IRL thickness after immunization against MOG35-55 in C57Bl/6J mice seems the most convenient model to study retinal neurodegeneration in EAE

Rotating Shallow Water Dynamics: Extra Invariant and the Formation of Zonal Jets

We show that rotating shallow water dynamics possesses an approximate (adiabatic-type) positive quadratic invariant, which exists not only at mid-latitudes (where its analogue in the quasigeostrophic equation has been previously investigated), but near the equator as well (where the quasigeostrophic equation is inapplicable). Deriving the extra invariant, we find "small denominators" of two kinds: (1) due to the triad resonances (as in the case of the quasigeostrophic equation) and (2) due to the equatorial limit, when the Rossby radius of deformation becomes infinite. We show that the "small denominators" of both kinds can be canceled. The presence of the extra invariant can lead to the generation of zonal jets. We find that this tendency should be especially pronounced near the equator. Similar invariant occurs in magnetically confined fusion plasmas and can lead to the emergence of zonal flows.Comment: 29 pages, 4 figure

Comparison of Vaginal Hysterectomy Techniques and Interventions for Benign Indications: A Systematic Review

OBJECTIVE: To create evidence-based clinical practice guidelines based on a systematic review of published literature regarding the risks and benefits of available preoperative, intraoperative, and postoperative technical steps and interventions at the time of vaginal hysterectomy for benign indications. DATA SOURCES: We systematically searched the literature to identify studies that compared technical steps or interventions during the preoperative, intraoperative, and postoperative periods surrounding vaginal hysterectomy. We searched MEDLINE, Cochrane Central Register of Controlled Trials, Health Technology Assessments, and ClinicalTrials.gov from their inception until April 10, 2016, using the MeSH term "Hysterectomy, Vaginal" and associated text words. We included comparative studies, single-group studies, and systematic reviews published in English. METHODS OF STUDY SELECTION: We double-screened 4,250 abstracts, identifying 60 eligible studies. Discrepancies were adjudicated by a third reviewer. We followed standard systematic review methodology and the Grades for Recommendation, Assessment, Development and Evaluation approach to evaluate the evidence and generate guideline recommendations. TABULATION, INTEGRATION, AND RESULTS: Because of limited literature, only 16 perioperative risks, technical steps, and interventions were identified: obesity, large uteri, prior surgery, gonadotropin-releasing hormone agonists, vaginal antisepsis, bilateral salpingo-oophorectomy, morcellation, apical closure, uterine sealers, hemostatic injectants, hot cone, retractor, cystoscopy, vaginal packing, bladder management, and accustimulation. We organized and reported these as four domains: patient selection, preoperative, intraoperative, and postoperative. We did not identify any patient characteristics precluding a vaginal approach; chlorhexidine or povidone is appropriate for vaginal antisepsis; vasopressin decreases blood loss by 130 cc; tissue-sealing devices decrease blood loss by 44 cc and operative time by 15 minutes with uncertain complication implications; vertical cuff closure results in 1-cm increased vaginal length; either peritoneum or epithelium can be used for colpotomy closure; and routine vaginal packing is not advised. CONCLUSION: Minimal data exist to guide surgeons with respect to planning and performing a vaginal hysterectomy. This study identifies available information and future areas for investigation

Exploring the influence of ancient and historic megaherbivore extirpations on the global methane budget

Globally, large-bodied wild mammals are in peril. Because “megamammals” have a disproportionate influence on vegetation, trophic interactions, and ecosystem function, declining populations are of considerable conservation concern. However, this is not new; trophic downgrading occurred in the past, including the African rinderpest epizootic of the 1890s, the massive Great Plains bison kill-off in the 1860s, and the terminal Pleistocene extinction of megafauna. Examining the consequences of these earlier events yields insights into contemporary ecosystem function. Here, we focus on changes inmethane emissions, produced as a byproduct of enteric fermentation by herbivores. Although methane is ∼200 times less abundant than carbon dioxide in the atmosphere, the greater efficiency of methane in trapping radiation leads to a significant role in radiative forcing of climate. Using global datasets of late Quaternary mammals, domestic livestock, and human population from the United Nations as well as literature sources, we develop a series of allometric regressions relating mammal body mass to population density and CH4 production, which allows estimation of methane production by wild and domestic herbivores for each historic or ancient time period. We find the extirpation ofmegaherbivores reduced global enteric emissions between 2.2–69.6 Tg CH4 y−1 during the various time periods, representing a decrease of 0.8–34.8% of the overall inputs to tropospheric input. Our analyses suggest that large-bodied mammals have a greater influence on methane emissions than previously appreciated and, further, that changes in the source pool from herbivores can influence global biogeochemical cycles and, potentially, climate

ErbB2 Signaling Increases Androgen Receptor Expression in Abiraterone-Resistant Prostate Cancer

Purpose: ErbB2 signaling appears to be increased and may enhance AR activity in a subset of CRPC, but agents targeting ErbB2 have not been effective. This study was undertaken to assess ErbB2 activity in abiraterone-resistant prostate cancer (PCa), and determine whether it may contribute to androgen receptor (AR) signaling in these tumors. Experimental Design: AR activity and ErbB2 signaling were examined in the radical prostatectomy specimens from a neoadjuvant clinical trial of leuprolide plus abiraterone, and in the specimens from abiraterone-resistant CRPC xenograft models. The effect of ErbB2 signaling on AR activity was determined in two CRPC cell lines. Moreover, the effect of combination treatment with abiraterone and an ErbB2 inhibitor was assessed in a CRPC xenograft model. Results: We found that ErbB2 signaling was elevated in residual tumor following abiraterone treatment in a subset of patients, and was associated with higher nuclear AR expression. In xenograft models, we similarly demonstrated that ErbB2 signaling was increased and associated with AR reactivation in abiraterone-resistant tumors, while ERBB2 message level was not changed. Mechanistically, we show that ErbB2 signaling and subsequent activation of the PI3K/AKT signaling stabilizes AR protein. Inhibitors targeting ErbB2/PI3K/AKT pathway disrupt AR transcriptional activity. Furthermore, concomitantly treating CRPC xenograft with abiraterone and an ErbB2 inhibitor, lapatinib, blocked AR reactivation and suppressed tumor progression. Conclusions: ErbB2 signaling is elevated in a subset of abiraterone-resistant prostate cancer patients and stabilizes AR protein. Combination therapy with abiraterone and ErbB2 antagonists may be effective for treating the subset of CRPC with elevated ErbB2 activity

Supraphysiologic Testosterone Therapy in the Treatment of Prostate Cancer: Models, Mechanisms and Questions

Since Huggins defined the androgen-sensitive nature of prostate cancer (PCa), suppression of systemic testosterone (T) has remained the most effective initial therapy for advanced disease although progression inevitably occurs. From the inception of clinical efforts to suppress androgen receptor (AR) signaling by reducing AR ligands, it was also recognized that administration of T in men with castration-resistant prostate cancer (CRPC) could result in substantial clinical responses. Data from preclinical models have reproducibly shown biphasic responses to T administration, with proliferation at low androgen concentrations and growth inhibition at supraphysiological T concentrations. Many questions regarding the biphasic response of PCa to androgen treatment remain, primarily regarding the mechanisms driving these responses and how best to exploit the biphasic phenomenon clinically. Here we review the preclinical and clinical data on high dose androgen growth repression and discuss cellular pathways and mechanisms likely to be involved in mediating this response. Although meaningful clinical responses have now been observed in men with PCa treated with high dose T, not all men respond, leading to questions regarding which tumor characteristics promote response or resistance, and highlighting the need for studies designed to determine the molecular mechanism(s) driving these responses and identify predictive biomarkers