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

Microalgae production in fresh market wastewater and its utilization as a protein substitute in formulated fish feed for oreochromis spp.

Rapid growing of human population has led to increasing demand of aquaculture production. Oreochromis niloticus or known as tilapia is one of the most globally cultured freshwater fish due to its great adaptation towards extreme environment. Besides, farming of tilapia not only involves small scales farming for local consumption but also larger scales for international market which contributes to a foreign currency earning. Extensive use of fishmeal as feed for fish and for other animals indirectly caused an increasing depletion of the natural resource and may consequently cause economic and environmental unstable. Microalgae biomass seems to be a promising feedstock in aquaculture industry. It can be used for many purposes such as live food for fish larvae and dried microalgae to substitute protein material in fish feed. The microalgae replacement in fish feed formulation as protein alternative seem potentially beneficial for long term aqua-business sustainability. The present chapter discussed the potential of microalgae as an alternative nutrition in fish feed formulations, specifically Tilapia

Direct constraint on the distance of y2 Velorum from AMBER/VLTI observations

In this work, we present the first AMBER observations, of the Wolf-Rayet and O (WR+O) star binary system y2 Velorum. The AMBER instrument was used with the telescopes UT2, UT3, and UT4 on baselines ranging from 46m to 85m. It delivered spectrally dispersed visibilities, as well as differential and closure phases, with a resolution R = 1500 in the spectral band 1.95-2.17 micron. We interpret these data in the context of a binary system with unresolved components, neglecting in a first approximation the wind-wind collision zone flux contribution. We show that the AMBER observables result primarily from the contribution of the individual components of the WR+O binary system. We discuss several interpretations of the residuals, and speculate on the detection of an additional continuum component, originating from the free-free emission associated with the wind-wind collision zone (WWCZ), and contributing at most to the observed K-band flux at the 5% level. The expected absolute separation and position angle at the time of observations were 5.1±0.9mas and 66±15° respectively. However, we infer a separation of 3.62+0.11-0.30 mas and a position angle of 73+9-11°. Our analysis thus implies that the binary system lies at a distance of 368+38-13 pc, in agreement with recent spectrophotometric estimates, but significantly larger than the Hipparcos value of 258+41-31 pc

Near-Infrared interferometry of Eta Carinae with high spatial and spectral resolution using the VLTI and the AMBER instrument

We present the first NIR spectro-interferometry of the LBV Eta Carinae. The K band observations were performed with the AMBER instrument of the ESO Very Large Telescope Interferometer using three 8.2m Unit Telescopes with baselines from 42 to 89m. The aim of this work is to study the wavelength dependence of Eta Car's optically thick wind region with a high spatial resolution of 5 mas (11 AU) and high spectral resolution. The medium spectral resolution observations (R=1,500) were performed in the wavelength range around both the HeI 2.059 micron and the Br gamma 2.166 micron emission lines, the high spectral resolution observations (R=12,000) only in the Br gamma line region. In the K-band continuum, a diameter of 4.0 +/-0.2 mas (Gaussian FWHM, fit range 28-89m) was measured for Eta Car's optically thick wind region. If we fit Hillier et al. (2001) model visibilities to the observed AMBER visibilities, we obtain 50 % encircled-energy diameters of 4.2, 6.5 and 9.6mas in the 2.17 micron continuum, the HeI, and the Br gamma emission lines, respectively. In the continuum near the Br gamma line, an elongation along a position angle of 120+/-15 degrees was found, consistent with previous VLTI/VINCI measurements by van Boekel et al. (2003). We compare the measured visibilities with predictions of the radiative transfer model of Hillier et al. (2001), finding good agreement. Furthermore, we discuss the detectability of the hypothetical hot binary companion. For the interpretation of the non-zero differential and closure phases measured within the Br gamma line, we present a simple geometric model of an inclined, latitude-dependent wind zone. Our observations support theoretical models of anisotropic winds from fast-rotating, luminous hot stars with enhanced high-velocity mass loss near the polar regions.Comment: 22 pages, 14 figures, 2 tables; A&A in pres

Constraining the wind launching region in Herbig Ae stars: AMBER/VLTI spectroscopy of HD 104237

Astronomy and Astrophysics, 464, pp. 55-58, http://dx.doi.org./10.1051/0004-6361:20065719International audienc

A Profitability Analysis for an Aggregator in the Ancillary Services Market: An Italian Case Study

The integration of renewable energy sources into the energy system requires both new investment in network infrastructures, and the introduction of new models of energy management. In this framework, new structures of collaborations were born: the aggregator is one of them. It involves grouping different players of the power system, acting, however, as a single entity both when it participates in the electricity markets and sells services to the operator. In this work, a new methodology to determine the optimal revenue of a Unità Virtuali Abilitate Miste (UVAM), which is an Italian virtual energy unit managed by an aggregator, is proposed. The methodology is articulated in several steps, the core of which is represented by the two models: (1) a cost–benefit analysis in order to identify the main costs/benefits that impact on the UVAM’ revenues; and (2) a decision-making model based on the sensitive analysis to capture the optimal interaction between users and aggregator. The results show how, on varying the parameter costs depending on the aggregator-users’ strategy, it is possible to obtain different optimal “working-points”. Finally, the analysis identifies two main cost factors that impact on the optimal revenue: the Energy Management Platform and the Communication costs, confirming the importance of these parameters in the general economy of UVAM

Interferometric data reduction with AMBER/VLTI. Principle, estimators, and illustration

This is the author accepted manuscript. The final version is available from EDP Sciences via the DOI in this record.Aims. In this paper, we present an innovative data reduction method for single-mode interferometry. It has been specifically developed for the AMBER instrument, the three-beam combiner of the Very Large Telescope Interferometer, but it can be derived for any single-mode interferometer. Methods. The algorithm is based on a direct modelling of the fringes in the detector plane. As such, it requires a preliminary calibration of the instrument in order to obtain the calibration matrix that builds the linear relationship between the interferogram and the interferometric observable, which is the complex visibility. Once the calibration procedure has been performed, the signal processing appears to be a classical least-square determination of a linear inverse problem. From the estimated complex visibility, we derive the squared visibility, the closure phase, and the spectral differential phase. Results. The data reduction procedures have been gathered into the so-called amdlib software, now available for the community, and are presented in this paper. Furthermore, each step in this original algorithm is illustrated and discussed from various on-sky observations conducted with the VLTI, with a focus on the control of the data quality and the effective execution of the data reduction procedures. We point out the present limited performances of the instrument due to VLTI instrumental vibrations which are difficult to calibrate.The AMBER project4 was founded by the French Centre National de la Recherche Scientifique (CNRS), the Max Planck Institute für Radioastronomie (MPIfR) in Bonn, the Osservatorio Astrofisico di Arcetri (OAA) in Firenze, the French Region “Provence Alpes Côte D’Azur” and the European Southern Observatory (ESO). The CNRS funding has been made through the Institut National des Sciences de l’Univers (INSU) and its Programmes Nationaux (ASHRA, PNPS, PNP). The OAA co-authors acknowledge partial support from MIUR grants to the Arcetri Observatory: A LBT interferometric arm, and analysis of VLTI interferometric data and From Stars to Planets: accretion, disk evolution and planet formation and from INAF grants to the Arcetri Observatory Stellar and Extragalactic Astrophysics with Optical Interferometry. C. Gil work was supported in part by the Fundação para a Ciência e a Tecnologia through project POCTI/CTE-AST/55691/2004 from POCTI, with funds from the European program FEDER

Sex does not influence the long-term outcome of matrix-assisted autologous chondrocyte transplantation

Purpose: Regenerative techniques for articular cartilage lesions demonstrated heterogeneous clinical results. Several factors may influence the outcome, with sex being one of the most debated. This study aimed at quantifying the long-term influence of sex on the clinical outcome obtained with a regenerative procedure for knee chondral lesions. Methods: Matrix-assisted autologous chondrocyte transplantation (MACT) was used to treat 235 knees which were prospectively evaluated with the International Knee Documentation Committee (IKDC), EuroQol visual analogue scale, and Tegner scores at 14-year mean follow-up. A multilevel analysis was performed with the IKDC subjective scores standardised according to the age/sex category of each patient and/or the selection of a match-paired subgroup to compare homogeneous men and women patients. Results: At 14 years, men and women showed a failure rate of 10.7% and 28.8%, respectively (p < 0.0005). An overall improvement was observed in both sexes. Women had more patellar lesions and men more condylar lesions (p = 0.001), and the latter also presented a higher preinjury activity level (p < 0.0005). Men had significantly higher IKDC subjective scores at all follow-ups (at 14 years: 77.2 ± 18.9 vs. 62.8 ± 23.1; p < 0.0005). However, the analysis of homogeneous match-paired populations of men and women, with standardised IKDC subjective scores, showed no differences between men and women (at 14 years: −1.6 ± 1.7 vs. −1.9 ± 1.6). Conclusion: Men and women treated with MACT for knee chondral lesions presented a significant improvement and stable long-term results. When both sexes are compared with homogeneous match-paired groups, they have similar results over time. However, women present more often unfavourable lesion patterns, which proved more challenging in terms of long-term outcome after MACT. Level of Evidence: Level II

Constraining the wind launching region in Herbig Ae stars: AMBER/VLTI spectroscopy of HD 104237

This is the author accepted manuscript. The final version is available from EDP Sciences via the DOI in this record.Aims. We investigate the origin of the Brγ emission of the Herbig Ae star HD 104237 on Astronomical Unit (AU) scales. Methods. Using AMBER/VLTI at a spectral resolution R = 1500 we spatially resolve the emission in both the Brγ line and the adjacent continuum. Results. The visibility does not vary between the continuum and the Brγ line, even though the line is strongly detected in the spectrum, with a peak intensity 35% above the continuum. This demonstrates that the line and continuum emission have similar size scales. We assume that the K-band continuum excess originates in a “puffed-up” inner rim of the circumstellar disk, and discuss the likely origin of Brγ. Conclusions. We conclude that this emission most likely arises from a compact disk wind, launched from a region 0.2–0.5 AU from the star, with a spatial extent similar to that of the near infrared continuum emission region, i.e., very close to the inner rim location.This work has been partly supported by the MIUR COFIN grant 2003/027003-001 and 025227/2004 to the INAFOsservatorio Astrofisico di Arcetri. This project has benefited from funding from the French Centre National de la Recherche Scientifique (CNRS) through the Institut National des Sciences de l’Univers (INSU) and its Programmes Nationaux (ASHRA, PNPS). The authors from the French laboratories would like to thank the successive directors of the INSU/CNRS directors. C. Gil work was supported in part by the Fundac¸˜ao para a Ciˆencia e a Tecnologia through project POCTI/CTE-AST/55691/2004 from POCTI,with funds from the European program FEDER