Applications of Human Tissue-Engineered Blood Vessel Models to Study the Effects of Shed Membrane Microparticles from T-Lymphocytes on Vascular Function

Microparticles (MPs) are membrane vesicles harboring cell surface proteins and containing cytoplasmic components of the original cell. High levels of circulating MPs have been detected in pathological states associated with vascular dysfunction. We took advantage of the self-assembly method of tissue engineering to produce in vitro three vascular constructs from human vascular smooth muscle cells and fibroblasts to investigate the role of the adventitia in the modulation of vascular tone by MPs, comparing the contractile response of each of these constructs to histamine. The first two were composed of an adventitia (tissue-engineered vascular adventitia (TEVA)) or a media (tissue-engineered vascular media (TEVM)) solely, and the third one contained a media and an adventitia (tissue-engineered vascular media and adventitia (TEVMA)). In the three constructs, the results show that histamine induces contraction insensitive to blockade of inducible nitric oxide (NO) synthase (iNOS) and cyclooxygenase-2 (COX-2) and not affected by MP treatment. MPs decreased NO production and nuclear factor (NF)-κB expression but did not affect superoxide anion (O2−) release in TEVA. MPs enhanced NF-κB expression but did not affect iNOS and COX-2 expression or NO or O2− release in TEVM. In TEVMA, MPs did not enhance NF-κB expression, but COX-2 expression was higher, and O2− release was lower. Thus, MPs affected NO, O2−, NF-κB, and COX-2 in a subtle fashion to maintain the contractile response to histamine. The use of tissue-engineered vascular constructs results in a better understanding of the effect of MPs on human adventitia and media

IceCube expectations for two high-energy neutrino production models at active galactic nuclei

We have determined the currently allowed regions of the parameter spaces of two representative models of diffuse neutrino flux from active galactic nuclei (AGN): one by Koers & Tinyakov (KT) and another by Becker & Biermann (BB). Our observable has been the number of upgoing muon-neutrinos expected in the 86-string IceCube detector, after 5 years of exposure, in the range 10^5 < E/GeV < 10^8. We have used the latest estimated discovery potential of the IceCube-86 array at the 5-sigma level to determine the lower boundary of the regions, while for the upper boundary we have used either the AMANDA upper bound on the neutrino flux or the more recent preliminary upper bound given by the half-completed IceCube-40 array (IC40). We have varied the spectral index of the proposed power-law fluxes, alpha, and two parameters of the BB model: the ratio between the boost factors of neutrinos and cosmic rays, Gamma_nu/Gamma_{CR}, and the maximum redshift of the sources that contribute to the cosmic-ray flux, zCRmax. For the KT model, we have considered two scenarios: one in which the number density of AGN does not evolve with redshift and another in which it evolves strongly, following the star formation rate. Using the IC40 upper bound, we have found that the models are visible in IceCube-86 only inside very thin strips of parameter space and that both of them are discarded at the preferred value of alpha = 2.7 obtained from fits to cosmic-ray data. Lower values of alpha, notably the values 2.0 and 2.3 proposed in the literature, fare better. In addition, we have analysed the capacity of IceCube-86 to discriminate between the models within the small regions of parameter space where both of them give testable predictions. Within these regions, discrimination at the 5-sigma level or more is guaranteed.Comment: 24 pages, 6 figures, v2: new IceCube-40 astrophysical neutrino upper bound and IceCube-86 discovery potential used, explanation of AGN flux models improved, only upgoing neutrinos used, conclusions strengthened. Accepted for publication in JCA

Molecular mechanisms of the cardiovascular protective effects of polyphenols

Epidemiological studies have reported a greater reduction in cardiovascular risk and metabolic disorders associated with diets rich in polyphenols. The antioxidant effects of polyphenols are attributed to the regulation of redox enzymes by reducing reactive oxygen species production from mitochondria, NADPH oxidases and uncoupled endothelial NO synthase in addition to also up-regulating multiple antioxidant enzymes. Although data supporting the effects of polyphenols in reducing oxidative stress are promising, several studies have suggested additional mechanisms in the health benefits of polyphenols. Polyphenols from red wine increase endothelial NO production leading to endothelium-dependent relaxation in conditions such as hypertension, stroke or the metabolic syndrome. Numerous molecules contained in fruits and vegetables can activate sirtuins to increase lifespan and silence metabolic and physiological disturbances associated with endothelial NO dysfunction. Although intracellular pathways involved in the endothelial effects of polyphenols are partially described, the molecular targets of these polyphenols are not completely elucidated. We review the novel aspects of polyphenols on several targets that could trigger the health benefits of polyphenols in conditions such as metabolic and cardiovascular disturbances

Lorentz breaking Effective Field Theory and observational tests

Analogue models of gravity have provided an experimentally realizable test field for our ideas on quantum field theory in curved spacetimes but they have also inspired the investigation of possible departures from exact Lorentz invariance at microscopic scales. In this role they have joined, and sometime anticipated, several quantum gravity models characterized by Lorentz breaking phenomenology. A crucial difference between these speculations and other ones associated to quantum gravity scenarios, is the possibility to carry out observational and experimental tests which have nowadays led to a broad range of constraints on departures from Lorentz invariance. We shall review here the effective field theory approach to Lorentz breaking in the matter sector, present the constraints provided by the available observations and finally discuss the implications of the persisting uncertainty on the composition of the ultra high energy cosmic rays for the constraints on the higher order, analogue gravity inspired, Lorentz violations.Comment: 47 pages, 4 figures. Lecture Notes for the IX SIGRAV School on "Analogue Gravity", Como (Italy), May 2011. V.3. Typo corrected, references adde

Performance study of a 3 x 1 x 1 m(3) dual phase liquid Argon Time Projection Chamber exposed to cosmic rays

This work would not have been possible without the support of the Swiss National Science Foundation, Switzerland; CEA and CNRS/IN2P3, France; KEK and the JSPS program, Japan; Ministerio de Ciencia e Innovacion in Spain under grants FPA2016-77347-C2, SEV-2016-0588 and MdM-2015-0509, Comunidad de Madrid, the CERCA program of the Generalitat de Catalunya and the fellowship (LCF/BQ/DI18/11660043) from "La Caixa" Foundation (ID 100010434); the Programme PNCDI III, CERN-RO, under Contract 2/2020, Romania; the U.S. Department of Energy under Grant No. DE-SC0011686. This project has received funding from the European Union's Horizon 2020 Research and Innovation program under Grant Agreement no. 654168. The authors are also grateful to the French government operated by the National Research Agency (ANR) for the LABEX Enigmass, LABEX Lyon Institute of Origins (ANR-10-LABX-0066) of the Universite de Lyon for its financial support within the program "Investissements d'Avenir" (ANR-11-IDEX-0007).We report the results of the analyses of the cosmic ray data collected with a 4 tonne (3x1x1 m(3)) active mass (volume) Liquid Argon Time-Projection Chamber (TPC) operated in a dual-phase mode. We present a detailed study of the TPC's response, its main detector parameters and performance. The results are important for the understanding and further developments of the dual-phase technology, thanks to the verification of key aspects, such as the extraction of electrons from liquid to gas and their amplification through the entire one square metre readout plain, gain stability, purity and charge sharing between readout views.Swiss National Science Foundation (SNSF)French Atomic Energy CommissionCentre National de la Recherche Scientifique (CNRS)High Energy Accelerator Research Organization (KEK)Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of ScienceSpanish Government FPA2016-77347-C2 SEV-2016-0588MdM-2015-0509Comunidad de MadridCERCA program of the Generalitat de CatalunyaLa Caixa Foundation LCF/BQ/DI18/11660043 100010434Programme PNCDI III, RomaniaCERN-RO, Romania 2/2020United States Department of Energy (DOE) SC0011686European Commission 654168Universite de Lyon ANR-10-LABX-0066 ANR-11-IDEX-000

Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE) Conceptual Design Report Volume 2: The Physics Program for DUNE at LBNF

The Physics Program for the Deep Underground Neutrino Experiment (DUNE) at the Fermilab Long-Baseline Neutrino Facility (LBNF) is described