Thermodynamics of phantom black holes in Einstein-Maxwell-Dilaton theory

A thermodynamic analysis of the black hole solutions coming from the Einstein-Maxwell-Dilaton theory (EMD) in 4D is done. By consider the canonical and grand-canonical ensemble, we apply standard method as well as a recent method known as Geometrothermodynamics (GTD). We are particularly interested in the characteristics of the so called phantom black hole solutions. We will analyze the thermodynamics of these solutions, the points of phase transition and their extremal limit. Also the thermodynamic stability is analyzed. We obtain a mismatch of the between the results of the GTD method when compared with the ones obtained by the specific heat, revealing a weakness of the method, as well as possible limitations of its applicability to very pathological thermodynamic systems. We also found that normal and phantom solutions are locally and globally unstable, unless for certain values of the coupled constant of the EMD action. We also shown that the anti-Reissner-Nordstrom solution does not posses extremal limit nor phase transition points, contrary to the Reissner-Nordstrom case.Comment: 23 pages, version accepted for publication in Physical Review

Multimodal Treatment Eliminates Cancer Stem Cells and Leads to Long-Term Survival in Primary Human Pancreatic Cancer Tissue Xenografts.

Copyright: 2013 Hermann et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.PURPOSE: In spite of intense research efforts, pancreatic ductal adenocarcinoma remains one of the most deadly malignancies in the world. We and others have previously identified a subpopulation of pancreatic cancer stem cells within the tumor as a critical therapeutic target and additionally shown that the tumor stroma represents not only a restrictive barrier for successful drug delivery, but also serves as a paracrine niche for cancer stem cells. Therefore, we embarked on a large-scale investigation on the effects of combining chemotherapy, hedgehog pathway inhibition, and mTOR inhibition in a preclinical mouse model of pancreatic cancer. EXPERIMENTAL DESIGN: Prospective and randomized testing in a set of almost 200 subcutaneous and orthotopic implanted whole-tissue primary human tumor xenografts. RESULTS: The combined targeting of highly chemoresistant cancer stem cells as well as their more differentiated progenies, together with abrogation of the tumor microenvironment by targeting the stroma and enhancing tissue penetration of the chemotherapeutic agent translated into significantly prolonged survival in preclinical models of human pancreatic cancer. Most pronounced therapeutic effects were observed in gemcitabine-resistant patient-derived tumors. Intriguingly, the proposed triple therapy approach could be further enhanced by using a PEGylated formulation of gemcitabine, which significantly increased its bioavailability and tissue penetration, resulting in a further improved overall outcome. CONCLUSIONS: This multimodal therapeutic strategy should be further explored in the clinical setting as its success may eventually improve the poor prognosis of patients with pancreatic ductal adenocarcinoma

First absolute measurements of fast-ion losses in the ASDEX Upgrade tokamak

A new diagnostic technique that allows to obtain absolute fluxes of fast-ion losses measured with absolutely calibrated scintillator based fast-ion loss detectors (FILD) is presented here. First absolute fluxes of fast-ion losses have been obtained in the ASDEX Upgrade tokamak. An instrument function that includes the scintillator efficiency, collimator geometry, optical transmission and camera efficiency has been constructed. The scintillator response to deuterium ions in the relevant energy range of fast-ions has been characterized using a tandem accelerator. Absolute flux of neutral beam injection (NBI) prompt losses has been obtained in magnetohydrodynamic quiescent plasmas. The temporal evolution of the heat load measured with FILD follows that measured at the FILD entrance obtained with an Infra-Red camera looking at the FILD detector head. ASCOT simulations are in good agreement with the absolute heat load of NBI prompt losses measured with FILD.Ministerio de Economía, Industria y Competitividad RYC-2011-09152, FIS2015-69362-P, ENE2012-31087EUROfusion Consortium PCIG11-GA-2012- 321455Comunidad Europea de la Energía Atómica 63305

Microenvironmental hCAP-18/LL-37 promotes pancreatic ductal adenocarcinoma by activating its cancer stem cell compartment

This is the peer reviewed version of the following article: Microenvironmental hCAP-18/LL-37 promotes pancreatic ductal adenocarcinoma by activating its cancer stem cell compartment. Gut 64.12 (2015): 1921-1935 and which has been published in final form at http://dx.doi.org/10.1136/gutjnl-2014-308935OBJECTIVES: The tumour stroma/microenvironment not only provides structural support for tumour development, but more importantly it provides cues to cancer stem cells (CSCs) that regulate their self-renewal and metastatic potential. This is certainly true for pancreatic ductal adenocarcinomas (PDAC), where tumour-associated fibroblasts, pancreatic stellate cells and immune cells create an abundant paracrine niche for CSCs via microenvironment-secreted factors. Thus understanding the role that tumour stroma cells play in PDAC development and CSC biology is of utmost importance. DESIGN: Microarray analyses, tumour microarray immunohistochemical assays, in vitro co-culture experiments, recombinant protein treatment approaches and in vivo intervention studies were performed to understand the role that the immunomodulatory cationic antimicrobial peptide 18/LL-37 (hCAP-18/LL-37) plays in PDAC biology. RESULTS: We found that hCAP-18/LL-37 was strongly expressed in the stroma of advanced primary and secondary PDAC tumours and is secreted by immune cells of the stroma (eg, tumour-associated macrophages) in response to tumour growth factor-β1 and particularly CSC-secreted Nodal/ActivinA. Treatment of pancreatic CSCs with recombinant LL-37 increased pluripotency-associated gene expression, self-renewal, invasion and tumourigenicity via formyl peptide receptor 2 (FPR2)- and P2X purinoceptor 7 receptor (P2X7R)-dependent mechanisms, which could be reversed by inhibiting these receptors. Importantly, in a genetically engineered mouse model of K-Ras-driven pancreatic tumourigenesis, we also showed that tumour formation was inhibited by either reconstituting these mice with bone marrow from cathelicidin-related antimicrobial peptide (ie, murine homologue of hCAP-18/LL-37) knockout mice or by pharmacologically inhibiting FPR2 and P2X7R. CONCLUSIONS: Thus, hCAP-18/LL-37 represents a previously unrecognised PDAC microenvironment factor that plays a critical role in pancreatic CSC-mediated tumourigenesis.CH: ERC Advanced Investigator Grant (Pa-CSC 233460), European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 256974 (EPC-TM-NET) and n° 602783 (CAM-PaC), the Subdirección General de Evaluación y Fomento de la Investigación, Fondo de Investigación Sanitaria (PS09/02129 & PI12/02643) and the Programa Nacional de Internacionalización de la I+D, Subprogramma: FCCI 2009 (PLE2009-0105; both Ministerio de Economía y Competitividad (es), Spain), BSJr: Rámon y Cajal Merit Award from the Ministerio de Economía y Competitividad, Spain and Clinic and Laboratory Integration Program (CLIP) grant from the Cancer Research Institute, NY, NY. MC: La Caixa Predoctoral Fellowshi

A multi-layered view of chemical and biochemical engineering

The contents of this article are based on the results of discussions the corresponding author has had since 2015 with the co-authors, who are members of academia and industry in Europe, on the scope and significance of chemical and biochemical engineering as a discipline. The result is a multi-layered view of chemical and biochemical engineering where the inner-layer deals with the fundamental principles and their application; the middle-layer deals with consolidation and expansion of the principles through a combination of science and engineering, leading to the development of sustainable technologies; and the outer-layer deals with integration of knowledge and collaboration with other disciplines to achieve a more sustainable society. Through this multi-layered view several important issues with respect to education, research and practice are highlighted together with current and future challenges and opportunities

Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease