Early Determination Research Articles

Differential impact of comorbidities and sex on pathophysiological pathways leading to heart failure with preserved ejection fraction

Abstract Background Heart failure (HF) with preserved ejection fraction (HFpEF) is a major public health problem worldwide, especially among the elderly. It is a complex syndrome characterised by multiple underlying comorbidities whose specific contribution is virtually impossible to disentangle in humans. As a result, treatment for HFpEF is still largely based on a "one-size-fits-all" approach, ignoring the specific pathophysiological substrate in each patient. Purpose we sought to identify the specific contribution of each HFpEF comorbidity to the development of this complex syndrome and to identify its earliest determinants and underlying mechanisms. Methods We used mouse models of ageing, obesity, hypertension, sleep apnoea, and hyperglycaemia to study the natural course of the syndrome and investigate the main determinants of HFpEF in each group separately and collectively. We followed the mice for up to 2.5 years and generated 100,000 individual data points (without omics), including echocardiography, vascular echography, lung ultrasound, histology and gene expression analyses in right and left ventricle, lung, liver and kidney. We developed new ad hoc statistical models to analyse all the longitudinal data. To identify the parameters that best determine the risk of HFpEF we used two complementary approaches: we first investigated features that could discriminate between mice with and without HFpEF and next, we investigated the changes associated with increased risk of HFpEF (time-to-HFpEF) among those animals that developed the syndrome. In addition, we used mass spectrometry proteomics to identify changes in protein expression and post-translational modification associated to HFpEF in each comorbidity. Results Age was the major contributor to HFpEF. Animals with HFpEF showed an increase in proteins involved in glycolysis, glycogen catabolism, and glutathione metabolism compared to those that did not develop HF, suggesting a change in metabolic substrate. The main parameters associated with HFpEF at old age started changing already at middle age. All comorbidities contributed to HFpEF through routes that were partially common but that were also characterised by distinct features. Changes in the right ventricle and in large vessels were strongly associated with the development of HFpEF in some comorbidities. Neither myocardial inflammation nor fibrosis were associated with HFpEF. Female mice followed a rather common route to HFpEF, including an association with kidney fibrosis and myocardial hypertrophy, while the development of the syndrome in mice was more comorbidity-determined. Conclusions Mice with different comorbidities follow at least partially different routes to HFpEF that are further affected by sex-dependent differences. Our results suggest that patients would benefit from a more tailored approach depending on their specific underlying pathology and gender.Main changes associated with HFpEF

A NOEMA Molecular Line Scan of the Hubble Deep Field North: Improved Constraints on the CO Luminosity Functions and Cosmic Density of Molecular Gas

We present measurements of the CO luminosity functions (LFs) and the evolution of the cosmic molecular gas density out to z ∼ 6 based on an 8.5 arcmin2 spectral scan survey at 3 mm of the iconic Hubble Deep Field North (HDF-N) observed with the NOrthern Extended Millimeter Array (NOEMA). We use matched filtering to search for line emission from galaxies and determine their redshift probability distributions exploiting the extensive multiwavelength data for the HDF-N. We identify the seven highest-fidelity sources as CO emitters at 1 < z < 6, including the well-known submillimeter galaxy HDF 850.1 at z = 5.18. Four high-fidelity 3 mm continuum sources are found to be radio galaxies at z ≤ 1, plus HDF 850.1. We constrain the CO LFs in the HDF-N out to z ∼ 6, including a first measurement of the CO(5–4) LF at 〈z〉 = 5.0. The relatively large area and depth of the NOEMA HDF-N survey extends the existing LFs at 1 < z < 4 above the knee, yielding a somewhat lower density by 0.15–0.4 dex at the overlap region for the CO(2–1) and CO(3–2) transitions, attributed to cosmic variance. We perform a joint analysis of the CO LFs in the HDF-N and Hubble Ultra Deep Field from ASPECS, finding that they can be well described by a single Schechter function. The evolution of the cosmic molecular gas density from a joint analysis is in good agreement with earlier determinations. This implies that the impact of cosmic field-to-field variance on the measurements is consistent with previous estimates, adding to the challenges for simulations that model galaxies from first principles.

Gravity darkening and tidally perturbed stellar pulsation in the misaligned exoplanet system WASP-33

Aims. WASP-33 is one of the few δ Sct stars with a known planetary companion. By analyzing the stellar oscillations, we search for possible star-planet interactions in the pattern of the pulsation. Methods. We made use of the Transit and Light Curve Modeller to solve the light curve from the Transiting Exoplanet Survey Satellite. We include gravity darkening in our analysis. Results. The stellar oscillation pattern of WASP-33 clearly shows signs of several tidally perturbed modes. We find that there are peaks in the frequency spectrum that are at or near the 3rd, 12th, and 25th orbital harmonics (forb ∼ 0.82 d−1). Also, there is a prominent overabundance of pulsational frequencies rightward of the orbital harmonics, a characteristic of a tidally perturbed stellar pulsation, which is an outcome of star-planet interactions in the misaligned system. There are peaks in both the δ Sct and γ Dor ranges of the Fourier spectrum, implying that WASP-33 is a γ Dor – δ Sct hybrid pulsator. The transit light curves are best fitted by a gravity-darkened stellar model, and the planet parameters are consistent with earlier determinations.

A Post-Conjunction Re-Evaluation of the Calibration and Long-term Evolution of the STEREO-A Heliospheric Imagers

In two earlier articles (Tappin, Eyles and Davies in Solar Phys. 290, 2143, 2015, and Solar Phys. 292, 28, 2017), we used the stellar photometry to determine the calibration parameters and long-term trends of the Heliospheric Imagers (HI) on board the Solar Terrestrial Relations Observatory (STEREO). In this article we provide an update on these determinations for the ahead spacecraft (STEREO-A) to incorporate the interval after solar superior conjunction (when STEREO-B was non-operational). We describe the modifications needed to our photometry procedures to accommodate the reduced pointing stability following the switch-off of the spacecraft gyros shortly prior to conjunction. We find a small revision to the absolute levels is required. We also show that the very low rates of degradation (less than 0.2% per year) found in the earlier determinations have continued beyond solar conjunction.

Ages and Masses of Star Clusters in M33: a Multiwavelength Study

Abstract We combine archival images for the nearby galaxy M33 (Triangulum Galaxy) from the ultraviolet (UV) to the infrared to derive ages, masses, and extinctions for the young star cluster population, and compare our physical parameters with published ones. Our goal is to test the robustness of clusters ages and masses, and possibly improve on existing ones both by expanding the wavelength range of the spectral-energy distribution (SED) fits and by using more recent population synthesis models. The rationale for this experiment is to verify the sensitivity of the clusters physical parameters to observational setups and model choices that span those commonly found in the literature. We derive the physical parameters of 137 clusters, using SEDs measured in eight UV-to-I bands, including Hα, from GALEX and ground-based images. We also add the 24 μm image from the Spitzer Space Telescope to help break some age degeneracies. We find that our derived cluster ages show significant differences with earlier determinations, while the masses remain relatively insensitive to the fitting approach adopted. We also highlight an already known difficulty in recovering old, low-extinction clusters, as SED-fitting codes tend to prefer younger, higher extinction solutions when the extinction is a free parameter. We publish updated ages, masses, and extinctions, with uncertainties for all sample star clusters, together with their photometry. Given the proximity of M33, this represents an important population to secure for the study of star formation and cluster evolution in spirals.

Specification of the patterning of a ductal tree during branching morphogenesis of the submandibular gland

The development of ductal structures during branching morphogenesis relies on signals that specify ductal progenitors to set up a pattern for the ductal network. Here, we identify cellular asymmetries defined by the F-actin cytoskeleton and the cell adhesion protein ZO-1 as the earliest determinants of duct specification in the embryonic submandibular gland (SMG). Apical polarity protein aPKCζ is then recruited to the sites of asymmetry in a ZO-1-dependent manner and collaborates with ROCK signaling to set up apical-basal polarity of ductal progenitors and further define the path of duct specification. Moreover, the motor protein myosin IIB, a mediator of mechanical force transmission along actin filaments, becomes localized to vertices linking the apical domains of multiple ductal epithelial cells during the formation of ductal lumens and drives duct maturation. These studies identify cytoskeletal, junctional and polarity proteins as the early determinants of duct specification and the patterning of a ductal tree during branching morphogenesis of the SMG.

First Consistent Determination of the Basic Reproduction Number for the First Covid-19 Wave in 71 Countries from the SIR-Epidemics Model with a Constant Ratio of Recovery to Infection Rate

The box-shaped serial interval distribution and the analytical solution of the Susceptible Infectious-Recovered (SIR)-epidemics model with a constant time-independent ratio of the recovery (μ0) to infection rate (a0) are used to calculate the effective reproduction factor and the basic reproduction number R0. The latter depends on the positively valued net infection number x = 13.5(a0 − μ0) as R0(x) = x(1 − e−x)−1 which for all values of x is greater unity. This dependence differs from the simple relation R0 = a0/μ0. With the earlier determination of the values of k and a0 of the Covid-19 pandemic waves in 71 countries the net infection rates and the basic reproduction numbers for these countries are calculated.

Ionized Gas in the NGC 3077 Galaxy

The nearby dwarf galaxy NGC 3077 is known for its peculiar morphology, which includes numerous dust lanes and emission-line regions. The interstellar medium in this galaxy is subject to several perturbing factors. These are primarily the central starburst and tidal structures in the M 81 group. We present a comprehensive study of the state of ionization, kinematics, and chemical composition of ionized gas in NGC 3077, including both star-forming regions and diffuse ionized gas (DIG) at the periphery. We study gas motions in the H$\alpha$ line via high-resolution ($R\approx15\,000$) 3D spectroscopy with the scanning Fabry-Perot interferometer installed into SCORPIO-2 instrument attached to the 6-m telescope of the SAO RAS. Images in the main optical emission lines were acquired with MaNGaL photometer with a tunable filter at the 2.5-m telescope of the Caucasian Mountain Observatory of SAI MSU. We also used SCORPIO-2 to perform long-slit spectroscopy of the galaxy with a resolution of $R\approx1\,000$. Our estimate of the gas metallicity, $Z=0.6Z_\odot$, is significantly lower than the earlier determination, but agrees with the "luminosity--metallicity" dependence. Spatially resolved diagnostic diagrams of the emission-line ratios do not show correlations between the gas ionization state and its velocity dispersion, and this is most likely due to strong ionization by young stars, whereas the contribution of shocks to the excitation of emission lines is less important. We also studied the locations of multicomponent H$\alpha$ profiles and provide arguments suggesting that they are mostly associated with individual kinematic components along the line of sight and not with expanding shells as it was believed earlier. We also observe there a combination of wind outflow from star-forming regions and accretion from interstellar gas clouds in the M 81 group.

Transport coefficients from in-medium quarkonium dynamics

The in medium dynamics of heavy particles are governed by transport coefficients. The heavy quark momentum diffusion coefficient, $\kappa$, is an object of special interest in the literature, but one which has proven notoriously difficult to estimate, despite the fact that it has been computed by weak-coupling methods at next-to-leading order accuracy, and by lattice simulations of the pure SU(3) gauge theory. Another coefficient, $\gamma$, has been recently identified. It can be understood as the dispersive counterpart of $\kappa$. Little is known about $\gamma$. Both $\kappa$ and $\gamma$ are, however, of foremost importance in heavy quarkonium physics as they entirely determine the in and out of equilibrium dynamics of quarkonium in a medium, if the evolution of the density matrix is Markovian, and the motion, quantum Brownian; the medium could be a strongly or weakly coupled plasma. In this paper, using the relation between $\kappa$, $\gamma$ and the quarkonium in medium width and mass shift respectively, we evaluate the two coefficients from existing 2+1 flavor lattice QCD data. The resulting range for $\kappa$ is consistent with earlier determinations, the one for $\gamma$ is the first non-perturbative determination of this quantity.

Parameter Determination for the Eclipsing Long-Period Dwarf Nova EX Dra from Photometric Observations during Different Activity States of the System

The results of a long-term photometric observations of the cataclysmic variable EX Dra acquired between 2014 and 2016 at the Crimean Station of the Sternberg Astronomical Institute (24 nights, more than 10 500 measurements) are presented. The observations were performed using CCD photometers mounted on 50-cm and 60-cm telescopes in the visible and red, during both quiescence and the active state. For completeness, photometric observations obtained at the Ondrejov Observatory in 2010 in the V and R Johnson filters are also used in the analysis. The new observations of EX Dra are used to derive the orbital period of the system, which agrees well with earlier determinations. A combined model that takes into account the radiation fluxes from the gaseous stream and a hot spot on the lateral surface of the accretion disk is used to determine the parameters of the system components (white dwarf, red dwarf, accretion disk and hot spot, and gaseous stream). Variations of the parameters when the system changes from one activity state to the other are considered. Six light curves displaying unsatisfactory agreement between the observed and theoretical light curves can be successfully fitted using a version of the combined model that includes hot spots on the secondary’s surface. This model is able to qualitatively reproduce a secondary minima in the light curves that exhibits shifts of this minimum from phase 0.5. The parameters of dark spots on the red-dwarf surface were determined. The data obtained indicate that the outbursts in the EX Dra system are related to instability of the matter outflow from the secondary.

Hydrogen Limits Carbon in Liquid Iron

AbstractMelting experiments were performed on the Fe‐C‐H system to 127 GPa in a laser‐heated diamond anvil cell. On the basis of in situ and ex situ sample characterizations, we found that the solubility of carbon in liquid Fe correlates inversely with hydrogen concentration at ~60 GPa and ~3500 K, indicating that liquid Fe preferentially incorporates hydrogen rather than carbon under conditions with abundant C and H. While large amounts of both C and H may have been delivered to the growing Earth, C‐poor/H‐rich metals were likely added to the protocore in the late stages of core formation. We also obtained a melting curve of FeHx (x &gt; 1) far beyond the pressure range in earlier determinations. Its liquidus temperature was found to be 2380 K at 135 GPa, lower than those of Fe alloyed with the other possible core light elements. Relatively low core temperature is thus supported by the presence of hydrogen.

Intense C III] λλ1907,1909 emission from a strong Lyman continuum emitting galaxy

We have obtained the first complete ultraviolet (UV) spectrum of a strong Lyman continuum (LyC) emitter at low redshift – the compact, low-metallicity, star-forming galaxy J1154+2443 – with a Lyman continuum escape fraction of 46% discovered recently. The Space Telescope Imaging Spectrograph spectrum shows strong Lyα and C III] λ1909 emission, as well as O III] λ1666. Our observations show that strong LyC emitters can have UV emission lines with a high equivalent width (e.g. EW(C III]) = 11.7 ± 2.9 Å rest-frame), although their equivalent widths should be reduced due to the loss of ionizing photons. The intrinsic ionizing photon production efficiency of J1154+2443 is high, log(ξ0ion = 25.56 erg−1 Hz), comparable to that of other recently discovered z ~ 0.3−0.4 LyC emitters. Combining our measurements and earlier determinations from the literature, we find a trend of increasing ξ0ion with increasing C III] λ1909 equivalent width, which can be understood by a combination of decreasing stellar population age and metallicity. Simple ionization and density-bounded photoionization models can explain the main observational features including the UV spectrum of J1154+2443.

Statistical approach of pion parton distributions from Drell–Yan process

The quantum statistical approach proposed more than one decade ago was used to determine the parton distributions for the proton by considering a large set of accurate Deep Inelastic Scattering experimental results. We propose to extend this work to extract the parton distributions for the pion by using data on lepton pair production from various experiments. This global next-to-leading order QCD analysis leads to a good description of several Drell–Yan π−W data. The resulting parton distributions are compared with earlier determinations. We will also discuss the difference between nucleon and pion structure in the same approach.

Assessment of the upper respiratory tract in patients eligible for treatment with transverse maxillary expansion

Transverse maxillary hypoplasia may negatively affect respiration. Maxillary narrowing has to be treated early. An appliance for Rapid Maxillary Expansion (RME) is the most common method, and it aims to expand the skeletal base and maintain this width until a new bone has been formed to fill in the fissure. Aim. Comparison of the results of measurements of bone structures and of the upper airways on lateral teleroentgenograms of the head in patients with transverse maxillary hypoplasia and in patients with normal dimensions of the maxilla. Material and methods. The study was carried out in a group of 20 people with maxillary narrowing (10 girls and 10 boys) aged 7 to 10 years. The control group consisted of 20 lateral teleroentgenograms of patients (9 girls and 11 boys) of similar age treated for other malocclusions. The structures of the facial skeleton and the upper respiratory tract were assessed in teleroentgenograms after earlier determination of measurement points and planes according to selected parameters of the McNamara and Preston et al. methodology. The obtained results were analysed statistically using the Mann-Whitney's test. Results. Angular measurements showed statistically significantly smaller SNA and SNB angles in the study group compared to the control group. The analysis of linear measurements indicated a statistically significant larger dimension of the actual length of the midfacial segment (Co-A) and distance between the Sella point and the posterior nasal spine (PNS-S), and a smaller dimension of the posterior facial height (PFH) in the study group compared to the control group. The highest differences in upper respiratory tract measurements were noted in the Ba-ho-PNS angle, which was lower in the study group. The result was not statistically significant. Conclusions. No significant differences in cephalometric measurements of the upper airways were observed. There is a need to extend studies to include groups of patients with features of night apnoea and maxillary narrowing. &lt;b&gt;(Dargiewicz E, Szarmach IJ, Sawczuk M. Assessment of the upper respiratory tract in patients eligible for treatment with transverse maxillary expansion. Orthod Forum 2018; 14: 97-105)&lt;/b&gt;

The Dependence of Convective Core Overshooting on Stellar Mass: Additional Binary Systems and Improved Calibration

Abstract Many current stellar evolution models assume some dependence of the strength of convective core overshooting on mass for stars more massive than 1.1–1.2 M ☉, but the adopted shapes for that relation have remained somewhat arbitrary for lack of strong observational constraints. In previous work, we compared stellar evolution models to well-measured eclipsing binaries to show that, when overshooting is implemented as a diffusive process, the fitted free parameter f ov rises sharply up to about 2 M ☉, and remains largely constant thereafter. Here, we analyze a new sample of eight binaries selected to be in the critical mass range below 2 M ☉ where f ov is changing the most, nearly doubling the number of individual stars in this regime. This interval is important because the precise way in which f ov changes determines the shape of isochrones in the turnoff region of ∼1–5 Gyr clusters, and can thus affect their inferred ages. It also has a significant influence on estimates of stellar properties for exoplanet hosts, on stellar population synthesis, and on the detailed modeling of interior stellar structures, including the calculation of oscillation frequencies that are observable with asteroseismic techniques. We find that the derived f ov values for our new sample are consistent with the trend defined by our earlier determinations, and strengthen the relation. This provides an opportunity for future series of models to test the new prescription, grounded on observations, against independent observations that may constrain overshooting in a different way.

Detection of the rapid variability in the Q2237+0305 quasar

Rapid intrinsic variability has been detected for the first time in the Einstein Cross QSO 2237+0305, a radio quiet flat spectrum quasar at z=1.7 that is quadruply lensed by a foreground galaxy at z=0.04. The observed short-period event at the time scale of several days and with amplitudes of about 0.1-0.2 mag can be traced in the light curves of the 2004 observing season for all macroimages and in all the three filters (V, R and I). The accuracy of the existing estimates of the time delays in Q2237+0305 is insufficient to either confirm or disprove the estimations of time delays based on the lens models of this system, especially taking into account the presence of strong microlensing events. The detected short-period variations in the Q2237+0305 light curves have made possible to obtain new estimates of the time delays, which are more accurate as compared to the earlier determinations by other authors.

Rate Constant of the Reaction between CH3O2 Radicals and OH Radicals Revisited.

The reaction between CH3O2 and OH radicals has been studied in a laser photolysis cell using the reaction of F atoms with CH4 and H2O for the simultaneous generation of both radicals, with F atoms generated through 248 nm photolysis of XeF2. An experimental setup combining cw-Cavity Ring Down Spectroscopy (cw-CRDS) and high repetition rate laser-induced fluorescence (LIF) to a laser photolysis cell has been used. The absolute concentration of CH3O2 was measured by cw-CRDS, while the relative concentration of OH(v = 0) radicals was determined by LIF. To remove dubiety from the quantification of CH3O2 by cw-CRDS in the near-infrared, its absorption cross section has been determined at 7489.16 cm-1 using two different methods. A rate constant of k1 = (1.60 ± 0.4) × 10-10 cm3 s-1 has been determined at 295 K, nearly a factor of 2 lower than an earlier determination from our group ((2.8 ± 1.4) × 10-10 cm3 s-1) using CH3I photolysis as a precursor. Quenching of electronically excited I atoms (from CH3I photolysis) in collision with OH(v = 0) is suspected to be responsible for a bias in the earlier, fast rate constant.

Changes in dermal matrix in the absence of Rac1 in keratinocytes.

Keratinocytes, in response to irritants, secrete pro-inflammatory mediators which recruit and activate immune and mesenchymal cells, including fibroblasts, to repair the skin. Fibroblasts respond by synthesising collagen and promoting the crosslinking extracellular matrix (ECM). We recently showed that the deletion of Rac1 in keratinocytes causes heightened inflammation due to aberrant crosstalk with immune cells. Indeed, the skin of these mice shows a higher inflammatory response to the induction of irritant contact dermatitis (ICD), and also even to treatment with a vehicle alone, compared with controls. As inflammation is intimately linked with fibrotic disease in the skin, this raised the question as to whether this deletion may also affect the deposition and arrangement of the dermal ECM. This study assessed the effects of Rac1 deletion in keratinocytes and of the heightened inflammatory status by induction of ICD on the tissue localisation and arrangements of dermal collagen. Qualitative analysis did not reveal evidence for the formation of pathologies in the dermis. However, quantitative analysis did reveal some perturbations in the dermal matrix, namely that only the combination of the lack of Rac1 and ICD affects the architectural organisation of the dermal collagen, and that a higher inflammatory state in the tissue (i.e. when Rac1 is deleted in the keratinocytes or ICD is induced in the skin, or a combination of both) influences the diameter of the collagen fibrils. It is proposed that this increase in the diameter of collagen fibrils due to inflammation may serve as pre-fibrotic marker enabling earlier determination of fibrosis and earlier treatment. This study has revealed previously unknown effects on the ECM due to the deletion of Rac1 in keratinocytes.

Abstract 5223: A novel pro-angiogenic role for IDO1 in inflammatory tumor promotion

Abstract Chronic inflammation is a major contributing factor in cancer, but, due to the complex multifactorial nature of inflammation, there remains limited understanding of specific pathogenic determinants that might be targeted therapeutically. The tryptophan-catabolizing enzyme IDO1 (indoleamine 2,3-dioxygenase) has emerged as an intriguing, pro-tumorigenic regulator of immune function in this regard. Because IDO1 can be elevated in chronic inflammatory states even prior to the initiation of cancer, it may represent one of the earliest determinants directing the immune response towards supporting rather than eliminating tumors. Genetic studies in mice have clearly established the tumor-promoting role of IDO1, but what this actually entails remains uncertain. Here we present evidence to support the novel hypothesis that a principle means by which IDO1 facilitates tumorigenesis is by mitigating immune-based angiostasis. Tumor angiogenesis is characterized by excessive and disorganized blood vessel growth much like that induced by ischemia where immune cells have been shown to be important for limiting neovascularization. Likewise, an anti-angiogenic response may be a factor in tumor immunity. In particular, IFNγ, an inflammatory cytokine, long recognized as a major inducer of IDO1, has been shown to exert angiostatic activity against developing tumors, which was implicated in these studies as the primary mechanism for both CD4 and CD8 T cell dependent tumor rejection. Our recently reported finding that the loss of IDO1 resulted in diminished pulmonary vascularization (Smith, Cancer Discovery 2012) suggested the possibility that IDO1 might be working at cross purposes to limit IFNγ-mediated angiostasis. In this same study IDO1 loss was also associated with the attenuated induction of the pro-angiogenic inflammatory cytokine IL6. To directly investigate the role of IDO1 in pathologic angiogenesis, we have utilized an oxygen-induced retinopathy (OIR) model. As predicted, neovascularization in the OIR model was significantly reduced in Ido1-/- mice. Consistent with the hypothesis that IDO1 supports neovascularization primarily by counteracting the angiostatic activity of IFNγ, neovascularization in double knockout Ifng-/- Ido1-/- mice reverted back to wild type levels. Il6-/- mice, on the other hand, exhibited reduced neovascularization which was likewise reversed by the concurrent elimination of IFNγ. In conjunction with these angiogenesis studies, we have also examined pulmonary metastasis development by 4T1 breast carcinoma isografts. Loss of either IDO1 or IL6 resulted in resistance to pulmonary metastases that, in both cases, was abrogated by the concurrent loss of IFNγ. Taken together, these findings have led us to propose a conceptually novel working hypothesis that, in the context of an inflammatory cytokine milieu, IDO1 plays a key role in supporting tumor angiogenesis. Citation Format: Arpita Mondal, James B. DuHadaway, Erika Sutanto-Ward, Courtney Smith, George C. Prendergast, Arturo Bravo-Nuevo, Alexander J. Muller. A novel pro-angiogenic role for IDO1 in inflammatory tumor promotion. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5223. doi:10.1158/1538-7445.AM2015-5223

New constraints on the CH4vertical profile in Uranus and Neptune fromHerschelobservations

Dedicated line observations of CH4 rotational lines performed with Herschel /PACS and HIFI in 2009–2011 provide new inferences of the mean methane profile in the upper tropospheres and stratospheres of Uranus and Neptune. At Uranus, CH4 is found to be near saturation, with a ~9 × 10-4 tropopause/lower stratosphere mole fraction. This is nominally six times larger than inferred from Spitzer in 2007, although reconciliation may be possible if the CH4 abundance decreases sharply from ~100 to 2 mbar. This unexpected situation might reflect heterogeneous conditions in Uranus’ stratosphere, with local CH4 depletions and heating associated with downwelling motions. Higher CH4 abundances compared to values inferred under solstitial conditions by Voyager in 1989 suggest that atmospheric mixing is effectively subdued at high latitudes and/or is time-variable. At Neptune, the mid-stratosphere CH4 abundance is (1.15 ± 0.10) × 10-3 , in agreement with earlier determinations and indicative of either leakage through a warmer polar region or upwelling at low or middle latitudes. On both planets, spatially resolved observations of temperature and methane in the stratosphere are needed to further identify the physical processes at work.