Gravitational-wave energy and other fluxes in ghost-free bigravity

One of the key ingredients for making binary waveform predictions in a beyond-GR theory of gravity is understanding the energy and angular momentum carried by gravitational waves and any other radiated fields. Identifying the appropriate energy functional is unclear in Hassan-Rosen bigravity, a ghost-free theory with one massive and one massless graviton. The difficulty arises from the new degrees of freedom and length scales which are not present in GR, rendering an Isaacson-style averaging calculation ambiguous. In this article we compute the energy carried by gravitational waves in bigravity starting from the action, using the canonical current formalism. The canonical current agrees with other common energy calculations in GR, and is unambiguous (modulo boundary terms), making it a convenient choice for quantifying the energy of gravitational waves in bigravity or any diffeomorphism-invariant theories of gravity. This calculation opens the door for future waveform modeling in bigravity to correctly include backreaction due to emission of gravitational waves.Comment: 18+4 pages, 2 figure

THYMOCYTES FROM MICE IMMUNIZED AGAINST AN ALLOGRAFT RENDER BONE-MARROW CELLS SPECIFICALLY CYTOTOXIC

Thymocytes from C57BL mice immunized with the DBA/2 lymphoma L5178Y exert in vitro an immunologically specific cytotoxic action against the target cells in the presence of bone-marrow cells. Neither the nonimmune bone marrow nor the immune thymocytes are by themselves cytotoxic. The cells in the bone marrow which take part in the cytotoxic action adhere to glass and are sensitive to anti-macrophage serum. These bone-marrow cells can also be rendered specifically cytotoxic by exposure to the supernatant obtained from a culture of immune thymocytes with the specific target cells. The thymocytes before they are confronted with the specific target cells are very radiosensitive; however, on coming into contact with the target cells, an immunologically specific increase in RNA synthesis occurs and thereafter the thymocytes' capacity to render bone-marrow cells cytotoxic is relatively radioresistant. Two classes of immune lymphocytes occur in mice immunized with allogeneic cells, those that are capable of killing target cells directly and those that produce a factor capable of rendering macrophages (or monocytes) specifically cytotoxic. In the thymus of immune animals only the latter are found while both categories are present in the spleen and lymph nodes of immune animals

The Efficacy of Peripheral Opioid Antagonists in Opioid-Induced Constipation and Postoperative Ileus: A Systematic Review of the Literature.

Opioid-induced constipation has a negative impact on quality of life for patients with chronic pain and can affect more than a third of patients. A related but separate entity is postoperative ileus, which is an abnormal pattern of gastrointestinal motility after surgery. Nonselective μ-opioid receptor antagonists reverse constipation and opioid-induced ileus but cross the blood-brain barrier and may reverse analgesia. Peripherally acting μ-opioid receptor antagonists target the μ-opioid receptor without reversing analgesia. Three such agents are US Food and Drug Administration approved. We reviewed the literature for randomized controlled trials that studied the efficacy of alvimopan, methylnaltrexone, and naloxegol in treating either opioid-induced constipation or postoperative ileus. Peripherally acting μ-opioid receptor antagonists may be effective in treating both opioid-induced bowel dysfunction and postoperative ileus, but definitive conclusions are not possible because of study inconsistency and the relatively low quality of evidence. Comparisons of agents are difficult because of heterogeneous end points and no head-to-head studies

THYMUS-DERIVED LYMPHOCYTES PRODUCE AN IMMUNOLOGICALLY SPECIFIC MACROPHAGEARMING FACTOR

Spleen cells from mice immunized with an allogeneic tumor when cultured with the specific tumor cells release into the supernatant a specific macrophage-arming factor(s) (SMAF) which binds nonspecifically to macrophages from both mice and rats and renders these cytotoxic to the specific tumor cells. SMAF also binds in an immunologically specific way to the target cells. SMAF-treated target cells grow normally in the absence of macrophages but are killed in the presence of normal macrophages. Thymus-derived cells are necessary for the production of SMAF since (a) after treatment with anti-θ serum immune spleen cells fail to release SMAF; (b) spleen cells from immunized T cell-deprived mice (thymectomized as adults followed by whole body irradiation and restored with bone marrow) fail to produce SMAF on stimulation with the specific target cells. While SMAF has the properties of a cytophilic antibody, it does not belong to one of the established classes of immunoglobulin since high activity is found after column separation in a fraction having a molecular weight between 50,000–60,000 daltons

Differential expression of prognostic proteomic markers in primary tumour, venous tumour thrombus and metastatic renal cell cancer tissue and correlation with patient outcome.

Renal cell carcinoma (RCC) is the most deadly of urological malignancies. Metastatic disease affects one third of patients at diagnosis with a further third developing metastatic disease after extirpative surgery. Heterogeneity in the clinical course ensures predicting metastasis is notoriously difficult, despite the routine use of prognostic clinico-pathological parameters in risk stratification. With greater understanding of pathways involved in disease pathogenesis, a number of biomarkers have been shown to have prognostic significance, including Ki67, p53, vascular endothelial growth factor receptor 1 (VEGFR1) and ligand D (VEGFD), SNAIL and SLUG. Previous pathway analysis has been from study of the primary tumour, with little attention to the metastatic tumours which are the focus of targeted molecular therapies. As such, in this study a tissue microarray from 177 patients with primary renal tumour, renal vein tumour thrombus and/or RCC metastasis has been created and used with Automated Quantitative Analysis (AQUA) of immunofluorescence to study the prognostic significance of these markers in locally advanced and metastatic disease. Furthermore, this has allowed assessment of differential protein expression between the primary tumours, renal vein tumour thrombi and metastases. The results demonstrate that clinico-pathological parameters remain the most significant predictors of cancer specific survival; however, high VEGFR1 or VEGFD can predict poor cancer specific survival on univariate analysis for locally advanced and metastatic disease. There was significantly greater expression of Ki67, p53, VEGFR1, SLUG and SNAIL in the metastases compared with the primary tumours and renal vein tumour thrombi. With the exception of p53, these differences in protein expression have not been shown previously in RCC. This confirms the importance of proliferation, angiogenesis and epithelial to mesenchymal transition in the pathogenesis and metastasis of RCC. Importantly, this work highlights the need for further pathway analysis of metastatic tumours for overcoming drug resistance and developing new therapies

Amphotericin forms an extramembranous and fungicidal sterol sponge.

For over 50 years, amphotericin has remained the powerful but highly toxic last line of defense in treating life-threatening fungal infections in humans with minimal development of microbial resistance. Understanding how this small molecule kills yeast is thus critical for guiding development of derivatives with an improved therapeutic index and other resistance-refractory antimicrobial agents. In the widely accepted ion channel model for its mechanism of cytocidal action, amphotericin forms aggregates inside lipid bilayers that permeabilize and kill cells. In contrast, we report that amphotericin exists primarily in the form of large, extramembranous aggregates that kill yeast by extracting ergosterol from lipid bilayers. These findings reveal that extraction of a polyfunctional lipid underlies the resistance-refractory antimicrobial action of amphotericin and suggests a roadmap for separating its cytocidal and membrane-permeabilizing activities. This new mechanistic understanding is also guiding development of what are to our knowledge the first derivatives of amphotericin that kill yeast but not human cells

Dynamics of defect formation

A dynamic symmetry-breaking transition with noise and inertia is analyzed. Exact solution of the linearized equation that describes the critical region allows precise calculation (exponent and prefactor) of the number of defects produced as a function of the rate of increase of the critical parameter. The procedure is valid in both the overdamped and underdamped limits. In one space dimension, we perform quantitative comparison with numerical simulations of the nonlinear nonautonomous stochastic partial differential equation and report on signatures of underdamped dynamics.Comment: 4 pages, LaTeX, 4 figures. Submitted to Physical Revie