Classical Setting and Effective Dynamics for Spinfoam Cosmology

We explore how to extract effective dynamics from loop quantum gravity and spinfoams truncated to a finite fixed graph, with the hope of modeling symmetry-reduced gravitational systems. We particularize our study to the 2-vertex graph with N links. We describe the canonical data using the recent formulation of the phase space in terms of spinors, and implement a symmetry-reduction to the homogeneous and isotropic sector. From the canonical point of view, we construct a consistent Hamiltonian for the model and discuss its relation with Friedmann-Robertson-Walker cosmologies. Then, we analyze the dynamics from the spinfoam approach. We compute exactly the transition amplitude between initial and final coherent spin networks states with support on the 2-vertex graph, for the choice of the simplest two-complex (with a single space-time vertex). The transition amplitude verifies an exact differential equation that agrees with the Hamiltonian constructed previously. Thus, in our simple setting we clarify the link between the canonical and the covariant formalisms.Comment: 38 pages, v2: Link with discretized loop quantum gravity made explicit and emphasize

Cosmological quantum entanglement

We review recent literature on the connection between quantum entanglement and cosmology, with an emphasis on the context of expanding universes. We discuss recent theoretical results reporting on the production of entanglement in quantum fields due to the expansion of the underlying spacetime. We explore how these results are affected by the statistics of the field (bosonic or fermionic), the type of expansion (de Sitter or asymptotically stationary), and the coupling to spacetime curvature (conformal or minimal). We then consider the extraction of entanglement from a quantum field by coupling to local detectors and how this procedure can be used to distinguish curvature from heating by their entanglement signature. We review the role played by quantum fluctuations in the early universe in nucleating the formation of galaxies and other cosmic structures through their conversion into classical density anisotropies during and after inflation. We report on current literature attempting to account for this transition in a rigorous way and discuss the importance of entanglement and decoherence in this process. We conclude with some prospects for further theoretical and experimental research in this area. These include extensions of current theoretical efforts, possible future observational pursuits, and experimental analogues that emulate these cosmic effects in a laboratory setting.Comment: 23 pages, 2 figures. v2 Added journal reference and minor changes to match the published versio

PCR-DGGE assessment of the bacterial diversity of breast milk in women with lactational infectious mastitis

<p>Abstract</p> <p>Background</p> <p>Infectious mastitis is a common condition during lactation and in fact, represents one of the main causes leading to a precocious weaning. The number of studies dealing with lactational mastitis is low and, up to now, the etiological diagnosis is frequently made on the basis of unspecific clinical signs. The aim of this study was to investigate the microbial diversity of breast milk in 20 women with lactational mastitis employing culture-dependent and culture-independent (PCR-DGGE) approaches.</p> <p>Methods</p> <p>Breast milk samples were cultured in different media to investigate the presence of bacteria and/or yeasts, and a total of 149 representative isolates were identified to the species level by 16S rRNA gene PCR sequencing. The microorganisms recovered were compared with those found by PCR-DGGE analysis. To identify the DGGE profiles two reference markers of different microbial species were constructed. Sequence analysis of unknown bands was also performed.</p> <p>Results</p> <p>Staphylococci were the dominant bacterial group and <it>Staphylococcus epidermidis </it>was the dominant species. In a lower number of samples, other bacteria (mainly streptococci and a few gram-negative species) were also identified. Globally, PCR-DGGE results showed a good correlation with those obtained by culture-based methods. However, although DNA bands corresponding to different lactic acid bacteria were detected, such bacteria could not be isolated from the milk samples.</p> <p>Conclusion</p> <p>Staphylococci seem to be the main etiological agents of human lactational mastitis. The combined use of culture and molecular techniques allowed a better characterization of the bacterial diversity in milk from women suffering from infectious mastitis. Our results suggest that this condition could be the result of a disbiotic process where some of the bacterial species usually present in human milk outgrow (staphylococci) while others disappear (lactobacilli or lactococci).</p

Prognostic importance of DNA from human papillomavirus in patients with oral squamous cell carcinoma

Survival of patients with oral squamous cell carcinoma (OSCC) is generally low, with the likelihood of locoregional recurrence or disease progression (LR/DP). Knowledge of prognostic factors for survival is key to achieving an understanding and increased survival. The present study aimed to identify prognostic factors for patients with OSCC, especially the presence of DNA from human papillomavirus (HPV). Retrospective cohort study including 119 patients with OSCC treated at the National Cancer Institute in Mexico City (2009-2013). Clinical information was obtained from patient records including LR/DP. Formalin-fixed, paraffin-embedded tissues were obtained and used for detecting DNA from different types of HPV. Potential prognostic factors for Overall Survival (OS) were analyzed using the Cox proportional hazards model. After model adjustment, factors associated with longer OS were a pre-treatment platelet count above 400,000/mm3 (HR=0.09, p=0.026) and response to primary treatment (HR=0.26, p=0.001). HPV DNA was present in 23 (19.3%) of the patients and importantly, type 16 found in 19 of them. Although survival of HPV-positive patients was longer, difference was not significant. However, among patients with LR/DP, HPV positivity was significantly associated with increased survival (HR=0.23, p=0.034). Importantly, survival was significantly different for HPV-positive patients with LR/DP > 6 months (HR=0.20, p=0.002), had higher absolute lymphocyte count at start of treatment (HR=0.50, p=0.028) or had local rescue treatment (HR=0.24, p=0.019). Although HPV positivity was not associated with a longer OS of OSCC patients, a better prognosis was significantly associated with HPV positivity and recurring or progressing disease, particularly with HPV type 16

Preclinical development of a humanized chimeric antigen receptor against B-cell maturation antigen for multiple myeloma

Multiple myeloma is a prevalent and incurable disease, despite the development of new and effective drugs. The recent development of chimeric antigen receptor (CAR)T cells has shown impressive results in the treatment of patients with relapsed or refractory hematologic B-cell malignancies. In recent years, B-cell maturation antigen (BCMA) has appeared as a promising antigen to target using a variety of immunotherapy treatments, including CART cells, for patients with multiple myeloma. To this end, we generated clinical-grade murine CART cells directed against BCMA, named ARI2m cells. Having demonstrated its efficacy, and in an attempt to avoid the immune rejection of CART cells by the patient, the single chain variable fragment was humanized, creating ARI2h cells. ARI2h cells showed comparable in vitro and in vivo efficacy to that of ARI2m cells, and superiority in cases of high tumor burden disease. In terms of inflammatory response, ARI2h cells produced less tumor necrosis factor-αand were associated with a milder in vivo toxicity profile. Large-scale expansion of both ARI2m and ARI2h cells was efficiently conducted following Good Manufacturing Practice guidelines, obtaining the target CART-cell dose required for treatment of multiple myeloma patients. Moreover, we demonstrated that soluble BCMA and BCMA released in vesicles both affect CAR-BCMA activity. In summary, this study sets the bases for the implementation of a clinical trial (EudraCT code: 2019-001472-11) to study the efficacy of ARI2h-cell treatment for patients with multiple myeloma

Holomorphic Simplicity Constraints for 4d Spinfoam Models

Within the framework of spinfoam models, we revisit the simplicity constraints reducing topological BF theory to 4d Riemannian gravity. We use the reformulation of SU(2) intertwiners and spin networks in term of spinors, which has come out from both the recently developed U(N) framework for SU(2) intertwiners and the twisted geometry approach to spin networks and spinfoam boundary states. Using these tools, we are able to perform a holomorphic/anti-holomorphic splitting of the simplicity constraints and define a new set of holomorphic simplicity constraints, which are equivalent to the standard ones at the classical level and which can be imposed strongly on intertwiners at the quantum level. We then show how to solve these new holomorphic simplicity constraints using coherent intertwiner states. We further define the corresponding coherent spin network functionals and introduce a new spinfoam model for 4d Riemannian gravity based on these holomorphic simplicity constraints and whose amplitudes are defined from the evaluation of the new coherent spin networks.Comment: 27 page

Extracellular NK histones promote immune cell anti-tumor activity by inducing cell clusters through binding to CD138 receptor

Background: Natural killer (NK) cells are important anti-tumor cells of our innate immune system. Their anti-cancer activity is mediated through interaction of a wide array of activating and inhibitory receptors with their ligands on tumor cells. After activation, NK cells also secrete a variety of pro-inflammatory molecules that contribute to the final immune response by modulating other innate and adaptive immune cells. In this regard, external proteins from NK cell secretome and the mechanisms by which they mediate these responses are poorly defined. Methods: TRANS-stable-isotope labeling of amino acids in cell culture (TRANS-SILAC) combined with proteomic was undertaken to identify early materials transferred between cord blood-derived NK cells (CB-NK) and multiple myeloma (MM) cells. Further in vitro and in vivo studies with knock-down of histones and CD138, overexpression of histones and addition of exogenous histones were undertaken to confirm TRANS-SILAC results and to determine functional roles of this material transferred. Results: We describe a novel mechanism by which histones are actively released by NK cells early after contact with MM cells. We show that extracellular histones bind to the heparan sulfate proteoglycan CD138 on the surface of MM cells to promote the creation of immune-tumor cell clusters bringing immune and MM cells into close proximity, and thus facilitating not only NK but also T lymphocyte anti-MM activity. Conclusion: This study demonstrates a novel immunoregulatory role of NK cells against MM cells mediated by histones, and an additional role of NK cells modulating T lymphocytes activity that will open up new avenues to design future immunotherapy clinical strategies

Which DSM validated tools for diagnosing depression are usable in primary care research? A systematic literature review

IntroductionDepression occurs frequently in primary care. Its broad clinical variability makes it difficult to diagnose. This makes it essential that family practitioner (FP) researchers have validated tools to minimize bias in studies of everyday practice. Which tools validated against psychiatric examination, according to the major depression criteria of DSM-IV or 5, can be used for research purposes

In-flight thermal experiments for LISA pathfinder: simulating temperature noise at the inertial sensors

Thermal Diagnostics experiments to be carried out on board LISA Pathfinder (LPF) will yield a detailed characterisation of how temperature fluctuations affect the LTP (LISA Technology Package) instrument performance, a crucial information for future space based gravitational wave detectors as the proposed eLISA. Amongst them, the study of temperature gradient fluctuations around the test masses of the Inertial Sensors will provide as well information regarding the contribution of the Brownian noise, which is expected to limit the LTP sensitivity at frequencies close to 1 mHz during some LTP experiments. In this paper we report on how these kind of Thermal Diagnostics experiments were simulated in the last LPF Simulation Campaign (November, 2013) involving all the LPF Data Analysis team and using an end-to-end simulator of the whole spacecraft. Such simulation campaign was conducted under the framework of the preparation for LPF operations

The LISA pathfinder mission

ISA Pathfinder (LPF), the second of the European Space Agency's Small Missions for Advanced Research in Technology (SMART), is a dedicated technology validation mission for future spaceborne gravitational wave detectors, such as the proposed eLISA mission. LISA Pathfinder, and its scientific payload - the LISA Technology Package - will test, in flight, the critical technologies required for low frequency gravitational wave detection: it will put two test masses in a near-perfect gravitational free-fall and control and measure their motion with unprecedented accuracy. This is achieved through technology comprising inertial sensors, high precision laser metrology, drag-free control and an ultra-precise micro-Newton propulsion system. LISA Pathfinder is due to be launched in mid-2015, with first results on the performance of the system being available 6 months thereafter. The paper introduces the LISA Pathfinder mission, followed by an explanation of the physical principles of measurement concept and associated hardware. We then provide a detailed discussion of the LISA Technology Package, including both the inertial sensor and interferometric readout. As we approach the launch of the LISA Pathfinder, the focus of the development is shifting towards the science operations and data analysis - this is described in the final section of the paper