•We observed a stellar occultation by Pluto on May 4, 2013.•The atmospheric pressure on Pluto at 1275 km was found to be 2.7 +/- 0.2 microbars from that event.•The only volatile transport models that ...are consistent with this new data have a high thermal inertia.•The high thermal inertia models have a global and collisional atmosphere throughout Pluto’s year.
Combining stellar occultation observations probing Pluto’s atmosphere from 1988 to 2013, and models of energy balance between Pluto’s surface and atmosphere, we find the preferred models are consistent with Pluto retaining a collisional atmosphere throughout its 248-year orbit. The occultation results show an increasing atmospheric pressure with time in the current epoch, a trend present only in models with a high thermal inertia and a permanent N2 ice cap at Pluto’s north rotational pole.
Aims. We report on the measurement and investigation of pulsed high-energy γ-ray emission from the Vela pulsar, PSR B0833−45, based on observations with the largest telescope of H.E.S.S., CT5, in ...monoscopic mode, and on data obtained with the Fermi-LAT. Methods. Data from 40.3 h of observations carried out with the H.E.S.S. II array from 2013 to 2015 have been used. A dedicated very low-threshold event reconstruction and analysis pipeline was developed to achieve the lowest possible energy threshold. Eight years of Fermi-LAT data were analysed and also used as reference to validate the CT5 telescope response model and analysis methods. Results. A pulsed γ-ray signal at a significance level of more than 15σ is detected from the P2 peak of the Vela pulsar light curve. Of a total of 15 835 events, more than 6000 lie at an energy below 20 GeV, implying a significant overlap between H.E.S.S. II-CT5 and the Fermi-LAT. While the investigation of the pulsar light curve with the LAT confirms characteristics previously known up to 20 GeV in the tens of GeV energy range, CT5 data show a change in the pulse morphology of P2, i.e. an extreme sharpening of its trailing edge, together with the possible onset of a new component at 3.4σ significance level. Assuming a power-law model for the P2 spectrum, an excellent agreement is found for the photon indices (Γ ≃ 4.1) obtained with the two telescopes above 10 GeV and an upper bound of 8% is derived on the relative offset between their energy scales. Using data from both instruments, it is shown however that the spectrum of P2 in the 10–100 GeV has a pronounced curvature; this is a confirmation of the sub-exponential cut-off form found at lower energies with the LAT. This is further supported by weak evidence of an emission above 100 GeV obtained with CT5. In contrast, converging indications are found from both CT5 and LAT data for the emergence of a hard component above 50 GeV in the leading wing (LW2) of P2, which possibly extends beyond 100 GeV. Conclusions. The detection demonstrates the performance and understanding of CT5 from 100 GeV down to the sub-20 GeV domain, i.e. unprecedented low energy for ground-based γ-ray astronomy. The extreme sharpening of the trailing edge of the P2 peak found in the H.E.S.S. II light curve of the Vela pulsar and the possible extension beyond 100 GeV of at least one of its features, LW2, provide further constraints to models of γ-Ray emission from pulsars.
Abstract
Magnetic fields in galaxies and galaxy clusters are believed to be the result of the amplification of intergalactic seed fields during the formation of large-scale structures in the ...universe. However, the origin, strength, and morphology of this intergalactic magnetic field (IGMF) remain unknown. Lower limits on (or indirect detection of) the IGMF can be obtained from observations of high-energy gamma rays from distant blazars. Gamma rays interact with the extragalactic background light to produce electron−positron pairs, which can subsequently initiate electromagnetic cascades. The gamma-ray signature of the cascade depends on the IGMF since it deflects the pairs. Here we report on a new search for this cascade emission using a combined data set from the Fermi Large Area Telescope and the High Energy Stereoscopic System. Using state-of-the-art Monte Carlo predictions for the cascade signal, our results place a lower limit on the IGMF of
B
> 7.1 × 10
−16
G for a coherence length of 1 Mpc even when blazar duty cycles as short as 10 yr are assumed. This improves on previous lower limits by a factor of 2. For longer duty cycles of 10
4
(10
7
) yr, IGMF strengths below 1.8 × 10
−14
G (3.9 × 10
−14
G) are excluded, which rules out specific models for IGMF generation in the early universe.
Here we present a novel hyperpolarization method, Chemical Reaction-Induced Multi-molecular Polarization (CRIMP), which could be applied to the study of several in vivo processes simultaneously ...including glycolysis, TCA cycle, fatty acid synthesis and pH mapping. Through the use of non-enzymatic decarboxylation, we generate four hyperpolarized imaging agents from hyperpolarized 1,2-(13)C pyruvic acid.
Von Hippel Lindau (VHL) inactivation, which is common in clear cell renal cell carcinoma (ccRCC), leads directly to the disruption of oxygen homoeostasis. VHL works through hypoxia-inducible factors ...(HIFs). Within this VHL-HIF system, prolyl hydroxylases (PHDs) are the intermediary proteins that initiate the degradation of HIFs. PHD isoform 3's (PHD3) role in ccRCC growth in vivo is poorly understood. Using viral transduction, we knocked down the expression of PHD3 in the human ccRCC cell line UMRC3. Compared with control cells transduced with scrambled vector (UMRC3-SC cells), PHD3-knockdown cells (UMRC3-PHD3KD cells) showed increased cell invasion, tumor growth, and response to sunitinib. PHD3 knockdown reduced HIF2α expression and increased phosphorylated epidermal growth factor (EGFR) expression in untreated tumor models. However, following sunitinib treatment, expression of HIF2α and phosphorylated EGFR were equivalent in both PHD3 knockdown and control tumors. PHD3 knockdown changed the overall redox state of the cell as seen by the increased concentration of glutathione in PHD3 knockdown tumors relative to control tumors. UMRC3-PHD3KD cells had increased proliferation in cell culture when grown in the presence of hydrogen peroxide compared to UMRC3-SC control cells. Our findings illustrate (1) the variable effect of PHD3 on HIF2α expression, (2) an inverse relationship between PHD3 expression and tumor growth in ccRCC animal models, and (3) the role of PHD3 in maintaining the redox state of UMRC3 cells and their proliferative rate under oxidative stress.
Context. The broadband spectral energy distributions (SED) of blazars show two distinct components which in leptonic models are associated with synchrotron and synchrotron self-Compton (SSC) emission ...of highly relativistic electrons. In some sources the SSC component dominates the synchrotron peak by one or more orders of magnitude implying that the electrons mainly cool by inverse Compton collisions with their self-made synchrotron photons. Therefore, the linear synchrotron loss of electrons, which is normally invoked in emission models, has to be replaced by a nonlinear loss rate depending on an energy integral of the electron distribution. This modified electron cooling changes significantly the emerging radiation spectra. Aims. It is the purpose of this work to apply this new cooling scenario to relativistic power-law distributed electrons, which are injected instantaneously into the jet. Methods. We assume a spherical, uniform, nonthermal source, where the distribution of the electrons is spatially and temporally isotropic throughout the source. We will first solve the differential equation of the volume-averaged differential number density of the electrons, and then discuss their temporal evolution. Since any non-linear cooling will turn into linear cooling after some time, we also calculated the electron number density for a combined cooling scenario consisting of both the linear and non-linear cooling. For all cases, we will also calculate analytically the emerging optically thin time-integrated synchrotron intensity spectrum, also named the fluence, and compare it to a numerical solution. Results. The first result is that the combined cooling scenario depends critically on the value of the injection parameter α0. For values α0 ≪ 1 the electrons cool mainly linear, while in the opposite case the cooling begins non-linear and becomes linear for later times. Secondly, in all cased we find that for small normalized frequencies f < 1 the fluence spectra F(f) exhibit power-laws with constant spectral indices F(f) ~ f − ϑ. We find for purely linear cooling ϑSYN = 1/2, and for purely non-linear cooling ϑSSC = 3/2. In the combined cooling scenario we obtain for the small injection parameter ϑ1 = 1/2, and for the large injection parameter ϑ2 = 3/2, which becomes ϑ1 = 1/2 for very small frequencies. These identical behaviors, as compared to the existing calculations for monoenergetically injected electrons, prove that the spectral behavior of the total synchrotron fluence is independent from the functional form of the energy injection spectrum.
When it concerns cancer care and cancer therapy, drug resistance is more than an obstacle to successful treatment; it is a major cause of frustration in our attempts to optimize drug development ...versus therapy development. Importantly, overcoming the challenges of drug resistance may provide invaluable clues about the origin and nature of cancer. From this perspective, we discuss how chemoresistance and chemosensitivity in cancer therapy could be directly linked to the stem cell origin of cancer. A stem cell theory of cancer stipulates that both normal stem cells and cancer stem cells are similarly endowed with robust efflux pumps, potent antiapoptotic mechanisms, redundant DNA repair systems, and abundant antioxidation reserves. Cancer stem cells, like their normal stem cell counterparts, are equipped with the same drug resistance phenotypes (e.g., ABC transporters, anti-apoptotic pathways, and DNA repair mechanisms). Drug resistance, like other cancer hallmarks (e.g., tumor heterogeneity and cancer dormancy), could be intrinsically ingrained and innately embedded within malignancy. We elaborate that cellular context and the microenvironment may attenuate the effects of cancer treatments. We examine the role of circadian rhythms and the value of chronotherapy to maximize efficacy and minimize toxicity. We propose that a stem cell theory of drug resistance and drug sensitivity will ultimately empower us to enhance drug development and enable us to improve therapy development in patient care.
ABSTRACT
We report on the detection of very high energy (VHE; E > 100 GeV) γ-ray emission from the BL Lac objects KUV 00311−1938 and PKS 1440−389 with the High Energy Stereoscopic System (H.E.S.S.). ...H.E.S.S. observations were accompanied or preceded by multiwavelength observations with Fermi/LAT, XRT and UVOT onboard the Swift satellite, and ATOM. Based on an extrapolation of the Fermi/LAT spectrum towards the VHE γ-ray regime, we deduce a 95 per cent confidence level upper limit on the unknown redshift of KUV 00311−1938 of $z$ < 0.98 and of PKS 1440−389 of $z$ < 0.53. When combined with previous spectroscopy results, the redshift of KUV 00311−1938 is constrained to 0.51 ≤ $z$ < 0.98 and of PKS 1440−389 to 0.14 ⪅ $z$ < 0.53.
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