Pancreatic ductal adenocarcinoma is a devastating disease with poor outcome, generally characterized by an excessive stroma component. The purpose of this study was to develop a simple and ...reproducible in vitro 3D-assay employing the main constituents of pancreatic ductal adenocarcinoma, namely pancreatic stellate and cancer cells.
A spheroid assay, directly co-culturing human pancreatic stellate cells with human pancreatic tumour cells in 3D was established and characterized by electron microscopy, immunohistochemistry and real-time RT-PCR. In order to facilitate the cell type-specific crosstalk analysis by real-time RT-PCR, we developed a novel in vitro 3D co-culture model, where the participating cell types were from different species, human and mouse, respectively. Using species-specific PCR primers, we were able to investigate the crosstalk between stromal and cancer cells without previous cell separation and sorting.
We found clear evidence for mutual influence, such as increased proliferation and a shift towards a more mesenchymal phenotype in cancer cells and an activation of pancreatic stellate cells towards the myofibroblast phenotype. Using a heterospecies approach, which we coined virtual sorting, confirmed the findings we made initially in the human-human spheroids.
We developed and characterized different easy to set up 3D models to investigate the crosstalk between cancer and stroma cells for pancreatic cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this paper we first make a review of the past annual production of electricity and the cumulative installed capacity for photovoltaic (PV) and concentrating solar power (CSP) technologies. This ...together with the annual costs of PV modules and CSP systems allows us the determination of the experience curves and the corresponding learning rates. Then, we go over a rigorous exposition of the methodology employed for the calculation of the value of the levelized cost of electricity (LCOE) for PV and CSP. Based on this knowledge, we proceed to establish a mathematical model which yields closed-form analytical expressions for the present value of the LCOE, as well as its future evolution (2010–2050) based on the International Energy Agency roadmaps for the cumulative installed capacity. Next, we explain in detail how specific values are assigned to the twelve independent variables which enter the LCOE formula: solar resource, discount and learning rates, initial cost and lifetime of the system, operational and maintenance costs, etc. With all this background, and making use of a simple computer simulation program, we can generate the following: sensitivity analysis curves, graphs on the evolution of the LCOE in the period 2010–2050, and calculations of the years at which grid parities will be reached. These representations prove to be very useful in energy planning policies, like tariff-in schemes, tax exemptions, etc., and in making investment decisions, since they allow, for a given location, to directly compare the costs of PV vs CSP power generation technologies for the period 2010–2050. Among solar technologies, PV seems always more appropriate for areas located in middle to high latitudes of the Earth, while CSP systems, preferably with thermal storage incorporated, yield their best performance in arid areas located at relatively low latitudes.
The main object of this paper consists in the development of a mathematical closed-form expression for the evaluation, in the period 2010–2050, of the levelized costs of energy (LCOE) of ...concentrating solar power (CSP) electricity. For this purpose, the LCOE is calculated using a life-cycle cost method, based on the net present value, the discounted cash flow technique and the technology learning curve approach. By this procedure, the LCOE corresponding to CSP electricity is calculated as a function of ten independent variables. Among these parameters, special attention has been put on the evaluation of the available solar resource, the analysis of the IEA predicted values for the cumulative installed capacity, the initial (2010) cost of the system, the discount and learning rates, etc. One significant contribution of our work is that the predicted evolution of the LCOEs strongly depend, not only on the particular values of the cumulative installed capacity function in the targeted years, but mainly on the specific curved time-paths which are followed by this function. The results obtained in this work are shown both graphically and numerically. Finally, the implications that the results could have in energy planning policies and grid parity calculations are discussed.
► A mathematical closed expression has been developed for calculating the evolution of CSP electricity costs. ► Our technique for the prediction of CSP electricity costs and grid parities is based on IEA Roadmaps. ► The time-table (2010–2050) of cumulative installed CSP capacity is key to electricity cost predictions. ► CSP grid parities can occur within next decade for sites with proper solar resources.
We report ac susceptibility and continuous wave and pulsed EPR experiments performed on GdW10 and GdW30 polyoxometalate clusters, in which a Gd3+ ion is coordinated to different polyoxometalate ...moieties. Despite the isotropic character of gadolinium as a free ion, these molecules show slow magnetic relaxation at very low temperatures, characteristic of single molecule magnets. For T≲200 mK, the spin-lattice relaxation becomes dominated by pure quantum tunneling events, with rates that agree quantitatively with those predicted by the Prokof'ev and Stamp model Phys. Rev. Lett. 80, 5794 (1998). The sign of the magnetic anisotropy, the energy level splittings, and the tunneling rates strongly depend on the molecular structure. We argue that GdW30 molecules are also promising spin qubits with a coherence figure of merit Q(M)≳50.
We present a sample of 10 low-mass active galactic nuclei (AGNs) selected from the 40-month Nuclear Spectroscopic Telescope Array (NuSTAR) serendipitous survey. The sample is selected to have robust ...NuSTAR detections at , to be at , and to have optical r-band magnitudes at least 0.5 mag fainter than an galaxy at its redshift. The median values of absolute magnitude, stellar mass, and 2-10 X-ray luminosity of our sample are , , and erg s−1, respectively. Five objects have detectable broad H emission in their optical spectra, indicating black hole masses of . We find that of the galaxies in our sample do not show AGN-like optical narrow emission lines, and one of the 10 galaxies in our sample, J115851+4243.2, shows evidence for heavy X-ray absorption. This result implies that a non-negligible fraction of low-mass galaxies might harbor accreting massive black holes that are missed by optical spectroscopic surveys and X-ray surveys. The mid-IR colors of our sample also indicate that these optically normal low-mass AGNs cannot be efficiently identified with typical AGN selection criteria based on Wide Field Infrared Survey Explorer colors. While the hard ( keV) X-ray-selected low-mass AGN sample size is still limited, our results show that sensitive NuSTAR observations are capable of probing faint hard X-ray emission originating from the nuclei of low-mass galaxies out to moderate redshift ( ), thus providing a critical step in understanding AGN demographics in low-mass galaxies.
Alignment in star-debris disc systems seen by Herschel Greaves, J. S; Kennedy, G. M; Thureau, N ...
Monthly notices of the Royal Astronomical Society. Letters,
02/2014, Letnik:
438, Številka:
1
Journal Article, Web Resource
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Many nearby main-sequence stars have been searched for debris using the far-infrared Herschel satellite, within the DEBRIS, DUNES and Guaranteed-Time Key Projects. We discuss here 11 stars of ...spectral types A-M where the stellar inclination is known and can be compared to that of the spatially resolved dust belts. The discs are found to be well aligned with the stellar equators, as in the case of the Sun's Kuiper belt, and unlike many close-in planets seen in transit surveys. The ensemble of stars here can be fitted with a star-disc tilt of 10°. These results suggest that proposed mechanisms for tilting the star or disc in fact operate rarely. A few systems also host imaged planets, whose orbits at tens of au are aligned with the debris discs, contrary to what might be expected in models where external perturbers induce tilts.
In higher plants ammonium (NH4+) assimilation occurs mainly through the glutamine synthetase/glutamate synthase (GS/GOGAT) pathway. Nevertheless, when plants are exposed to stress conditions, such as ...excess of ammonium, the contribution of alternative routes of ammonium assimilation such as glutamate dehydrogenase (GDH) and asparagine synthetase (AS) activities might serve as detoxification mechanisms. In this work, the in vivo functions of these pathways were studied after supplying an excess of ammonium to tomato (Solanum lycopersicum L. cv. Agora Hybrid F1) roots previously adapted to grow under either nitrate or ammonium nutrition. The short-term incorporation of labelled ammonium (15NH4+) into the main amino acids was determined by GC–MS in the presence or absence of methionine sulphoximine (MSX) and azaserine (AZA), inhibitors of GS and GOGAT activities, respectively. Tomato roots were able to respond rapidly to excess ammonium by enhancing ammonium assimilation regardless of the previous nutritional regime to which the plant was adapted to grow. The assimilation of 15NH4+ could take place through pathways other than GS/GOGAT, since the inhibition of GS and GOGAT did not completely impede the incorporation of the labelled nitrogen into major amino acids. The in vivo formation of Asn by AS was shown to be exclusively Gln-dependent since the root was unable to incorporate 15NH4+ directly into Asn. On the other hand, an in vivo aminating capacity was revealed for GDH, since newly labelled Glu synthesis occurred even when GS and/or GOGAT activities were inhibited. The aminating GDH activity in tomato roots responded to an excess ammonium supply independently of the previous nutritional regime to which the plant had been subjected.
Sweet perception promotes food intake, whereas that of bitterness is inhibitory. Surprisingly, the expression of sweet G protein-coupled taste receptor (GPCTR) subunits (T1R2 and T1R3) and bitter ...GPCTRs (T2R116, T2R118, T2R138 and T2R104), as well as the α-subunits of the associated signalling complex (αGustducin, Gα14 and αTransducin), in oral and extra-oral tissues from lean and obese mice, remains poorly characterized. We focused on the impact of obesity on taste receptor expression in brain areas involved in energy homeostasis, namely the hypothalamus and brainstem. We demonstrate that many of the GPCTRs and α-subunits are co-expressed in these tissues and that obesity decreases expression of T1R3, T2R116, Gα14, αTrans and TRPM5. In vitro high levels of glucose caused a prominent down-regulation of T1R2 and Gα14 expression in cultured hypothalamic neuronal cells, leptin caused a transient down-regulation of T1R2 and T1R3 expression. Intriguingly, expression differences were also observed in other extra-oral tissues of lean and obese mice, most strikingly in the duodenum where obesity reduced the expression of most bitter and sweet receptors. In conclusion, obesity influences components of sweet and bitter taste sensing in the duodenum as well as regions of the mouse brain involved in energy homeostasis, including hypothalamus and brainstem.
The aim of the present randomized trial was to compare high-dose therapy (HDT) with continued conventional chemotherapy in patients with multiple myeloma (MM) who responded to the initial treatment. ...From May 1994 to October 1999, 216 patients (122 men/94 women; stage II or III; Eastern Cooperative Oncology Group ECOG score less than 3) entered the study. Initial chemotherapy consisted of 4 cycles of alternating vincristine, BCNU, melphalan, cyclophosphamide, prednisone/vincristine, BCNU, Adriamycin, dexamethasone (VBMCP/VBAD). Responding patients were randomly assigned to receive 8 additional cycles of VBMCP/VBAD, intensification with melphalan 200 mg/m2, or melphalan 140 mg/m2 plus 12 Gy fractionated total body irradiation (TBI). One-hundred sixty-four patients were randomly assigned, 83 to continued chemotherapy and 81 to HDT. The complete remission (CR) rate was significantly higher with HDT (30% vs 11%; P = .002). However, progression-free survival (PFS) was not significantly different between HDT and conventional therapy (median, 42 vs 33 months; P = not significant NS), and overall survival (OS) was similar in both groups (median, 61 vs 66 months). Finally, survival after relapse was identical in the 2 arms (15.9 vs 16.4 months). In conclusion, these results show that HDT intensification, when given to myeloma patients who have responded to the initial chemotherapy, significantly increases the CR rate but has no significant impact on PFS or OS.
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