In recent years, studies of cancer development and recurrence have been influenced by the cancer stem cells (CSCs)/cancer-initiating cells (CICs) hypothesis. According to this, cancer is sustained by ...highly positioned, chemoresistant cells with extensive capacity of self renewal, which are responsible for disease relapse after chemotherapy. Growth of cancer cells as three-dimensional non-adherent spheroids is regarded as a useful methodology to enrich for cells endowed with CSC-like features. We have recently reported that cell cultures derived from malignant pleural effusions (MPEs) of patients affected by adenocarcinoma of the lung are able to efficiently form spheroids in non-adherent conditions supplemented with growth factors. By expression profiling, we were able to identify a set of genes whose expression is significantly upregulated in lung tumor spheroids versus adherent cultures. One of the most strongly upregulated gene was stearoyl-CoA desaturase (SCD1), the main enzyme responsible for the conversion of saturated into monounsaturated fatty acids. In the present study, we show both by RNA interference and through the use of a small molecule inhibitor that SCD1 is required for lung cancer spheroids propagation both in stable cell lines and in MPE-derived primary tumor cultures. Morphological examination and image analysis of the tumor spheroids formed in the presence of SCD1 inhibitors showed a different pattern of growth characterized by irregular cell aggregates. Electron microscopy revealed that the treated spheroids displayed several features of cellular damage and immunofluorescence analysis on optical serial sections showed apoptotic cells positive for the M30 marker, most of them positive also for the stemness marker ALDH1A1, thus suggesting that the SCD1 inhibitor is selectively killing cells with stem-like properties. Furthermore, SCD1-inhibited lung cancer cells were strongly impaired in their in vivo tumorigenicity and ALDH1A1 expression. These results suggest that SCD1 is a critical target in lung cancer tumor-initiating cells.
The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the ...surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30-80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy-corrected for geometrical effects-is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.
The emission of radio waves from air showers has been attributed to the so-called geomagnetic emission process. At frequencies around 50 MHz this process leads to coherent radiation which can be ...observed with rather simple setups. The direction of the electric field induced by this emission process depends only on the local magnetic field vector and on the incoming direction of the air shower. We report on measurements of the electric field vector where, in addition to this geomagnetic component, another component has been observed that cannot be described by the geomagnetic emission process. The data provide strong evidence that the other electric field component is polarized radially with respect to the shower axis, in agreement with predictions made by Askaryan who described radio emission from particle showers due to a negative charge excess in the front of the shower. Our results are compared to calculations which include the radiation mechanism induced by this charge-excess process.
On September 14, 2015 the Advanced LIGO detectors observed their first gravitational wave (GW) transient GW150914. This was followed by a second GW event observed on December 26, 2015. Both events ...were inferred to have arisen from the merger of black holes in binary systems. Such a system may emit neutrinos if there are magnetic fields and disk debris remaining from the formation of the two black holes. With the surface detector array of the Pierre Auger Observatory we can search for neutrinos with energy Eν above 100 PeV from pointlike sources across the sky with equatorial declination from about −65° to +60°, and, in particular, from a fraction of the 90% confidence-level inferred positions in the sky of GW150914 and GW151226. A targeted search for highly inclined extensive air showers, produced either by interactions of downward-going neutrinos of all flavors in the atmosphere or by the decays of tau leptons originating from tau-neutrino interactions in the Earth’s crust (Earth-skimming neutrinos), yielded no candidates in the Auger data collected within ±500 s around or 1 day after the coordinated universal time (UTC) of GW150914 and GW151226, as well as in the same search periods relative to the UTC time of the GW candidate event LVT151012. From the nonobservation we constrain the amount of energy radiated in ultrahigh-energy neutrinos from such remarkable events.
Here using the data of the Pierre Auger Observatory, we report on a search for signatures that would be suggestive of super-heavy particles decaying in the Galactic halo. From the lack of signal, we ...present upper limits for different energy thresholds above ≳108 GeV on the secondary by-product fluxes expected from the decay of the particles. Assuming that the energy density of these super-heavy particles matches that of dark matter observed today, we translate the upper bounds on the particle fluxes into tight constraints on the couplings governing the decay process as a function of the particle mass. Instantons, which are nonperturbative solutions to Yang-Mills equations, can give rise to decay channels otherwise forbidden and transform stable particles into metastable ones. Assuming such instanton-induced decay processes, we derive a bound on the reduced coupling constant of gauge interactions in the dark sector: αX ≲ 0.09, for 109 ≲ MX/GeV < 1019. Conversely, we obtain that, for instance, a reduced coupling constant αX = 0.09 excludes masses MX ≳ 3 x 1013 GeV . In the context of dark matter production from gravitational interactions alone during the reheating epoch, we derive constraints on the parameter space that involves, in addition to MX and αX, the Hubble rate at the end of inflation, the reheating efficiency, and the nonminimal coupling of the Higgs with curvature.
The determination of the primary energy of extensive air showers using the fluorescence detection technique requires an estimation of the energy carried away by particles that do not deposit all ...their energy in the atmosphere. This estimation is typically made using Monte Carlo simulations and thus depends on the assumed primary particle mass and on model predictions for neutrino and muon production. In this work we present a new method to obtain the invisible energy from events detected by the Pierre Auger Observatory. The method uses measurements of the muon number at ground level, and it allows us to significantly reduce the systematic uncertainties related to the mass composition and the high energy hadronic interaction models, and consequently to improve the estimation of the energy scale of the Pierre Auger Observatory.
We present a search for ultrarelativistic magnetic monopoles with the Pierre Auger observatory. Such particles, possibly a relic of phase transitions in the early Universe, would deposit a large ...amount of energy along their path through the atmosphere, comparable to that of ultrahigh-energy cosmic rays (UHECRs). The air-shower profile of a magnetic monopole can be effectively distinguished by the fluorescence detector from that of standard UHECRs. No candidate was found in the data collected between 2004 and 2012, with an expected background of less than 0.1 event from UHECRs. The corresponding 90% confidence level (C.L.) upper limits on the flux of ultrarelativistic magnetic monopoles range from 10−19(cm2 sr s)−1 for a Lorentz factor γ=109 to 2.5×10−21(cm2 sr s)−1 for γ=1012. These results-the first obtained with a UHECR detector-improve previously published limits by up to an order of magnitude.
Unilateral and solid-state nuclear magnetic resonance (NMR) analyses were performed on a parchment fragment of the Dead Sea Scroll (DSS). The analyzed sample belongs to the collection of ...non-inscribed and nontreated fragments of known archaeological provenance from the John Rylands University Library in Manchester. Therefore, it can be considered as original DSS material free from any contamination related to the post-discovery period. Considering the paramount significance of the DSS, noninvasive approaches and portable
in situ
nondestructive methods are of fundamental importance for the determination of composition, structure, and chemical–physical properties of the materials under study. NMR studies reveal low amounts of water content associated with very short proton relaxation times,
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, indicating a high level of deterioration of collagen molecules within scroll fragments. In addition,
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C cross-polarization magic-angle-spinning (CPMAS) NMR spectroscopy shows characteristic peaks of lipids whose presence we attribute to the production technology that did not involve liming. Extraction with chloroform led to the reduction of both lipid and protein signals in the
13
C CPMAS spectrum indicating probable involvement of lipids in parchment degradation processes. NMR absorption and relaxation measurements provide nondestructive, discriminative, and sensitive tools for studying the deterioration effects on the organization and properties of water and collagen within ancient manuscripts.
Fig
The state of deterioration of a Dead Sea scroll fragment was studied by means of
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H and
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C solid state NMR and proton
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relaxation measurements
We report a measurement of the energy spectrum of cosmic rays above 2.5×1018 eV based on 215030 events. New results are presented: at about 1.3×1019 eV, the spectral index changes from ...2.51±0.03(stat)±0.05(syst) to 3.05±0.05(stat)±0.10(syst), evolving to 5.1±0.3(stat)±0.1(syst) beyond 5×1019 eV, while no significant dependence of spectral features on the declination is seen in the accessible range. These features of the spectrum can be reproduced in models with energy-dependent mass composition. The energy density in cosmic rays above 5×1018 eV is 5.66±0.03(stat)±1.40(syst)×1053 erg Mpc-3.
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