The factors limiting the conductivity of fluorine‐doped tin dioxide (FTO) produced via atmospheric pressure chemical vapor deposition are investigated. Modeling of the transport properties indicates ...that the measured Hall effect mobilities are far below the theoretical ionized impurity scattering limit. Significant compensation of donors by acceptors is present with a compensation ratio of 0.5, indicating that for every two donors there is approximately one acceptor. Hybrid density functional theory calculations of defect and impurity formation energies indicate the most probable acceptor‐type defects. The fluorine interstitial defect has the lowest formation energy in the degenerate regime of FTO. Fluorine interstitials act as singly charged acceptors at the high Fermi levels corresponding to degenerately n‐type films. X‐ray photoemission spectroscopy of the fluorine impurities is consistent with the presence of substitutional FO donors and interstitial Fi in a roughly 2:1 ratio in agreement with the compensation ratio indicated by the transport modeling. Quantitative analysis through Hall effect, X‐ray photoemission spectroscopy, and calibrated secondary ion mass spectrometry further supports the presence of compensating fluorine‐related defects.
Compensating acceptor defects dramatically reduce electronic performance of F:SnO2 transparent conductor grown by chemical vapor deposition. Electron carrier mobilities are seen to be greatly diminished from the theoretically predicted optimum. Using hybrid density functional theory calculations and experimental methods, and analysis, the defect responsible for self‐compensation in F:SnO2 is determined to be the fluorine interstitial.
Melanocortin receptors have emerged as important targets with a very unusual versatility, as their widespread distribution on multiple tissues (e.g. skin, adrenal glands, brain, immune cells, ...exocrine glands) together with the variety of physiological processes they control (pigmentation, cortisol release, satiety mechanism, inflammation, secretions), place this family of receptors as genuine therapeutic targets for many disorders. This review focuses in the journey of the development of melanocortin receptors as therapeutic targets from the discovery of their existence in the early 1990 s to the approval of the first few drugs of this class. Two major areas of development characterise the current state of melanocortin drug development: their role in obesity, recently culminated with the approval of setmelanotide, and their potential for the treatment of chronic inflammatory and autoimmune diseases like rheumatoid arthritis, multiple sclerosis or fibrosis. The pro-resolving nature of these drugs offers the advantage of acting by mimicking the way our body naturally resolves inflammation, expecting fewer side effects and a more balanced (i.e. non-immunosuppressive) response from them. Here we also review the approaches followed for the design and development of novel compounds, the importance of the GPCR nature of these receptors in the process of drug development, therapeutic value, current challenges and successes, and the potential for the implementation of precision medicine approaches through the incorporation of genetics advances.
•Melanocortin (MC) drugs act by binding to five different melanocortin receptors.•Their role in multiple organ systems and GPCR nature makes them very attractive as drug targets.•Several MC drugs have already been approved for treating various conditions.•New MC compounds are under clinical development for the treatment of additional indications.•Deeper understanding of GPCR signalling modulation and structure will help design improved MC drugs.
Pressures on freshwater biodiversity in Southeast Asia are accelerating yet the status and conservation needs of many of the region's threatened fish species are unclear. This impacts the ability to ...implement conservation activities and to understand the effects of infrastructure developments and other hydrological changes. We used Local Ecological Knowledge from fishing communities on the Mekong River in the Siphandone waterscape, Lao PDR to estimate mean and mode last capture dates of eight rare or culturally significant fish species in order to provide conservation monitoring baselines. One hundred and twenty fishermen, from six villages, were interviewed. All eight species had been captured, by at least one of the interviewees, within the waterscape within the past year. However the mean and mode last capture dates varied between the species. Larger species, and those with higher Red List threat status, were caught less recently than smaller species of less conservation concern. The status of the Critically Endangered Pangasius sanitwongsei (mean last capture date 116.4 months) is particularly worrying suggesting severe population decline although cultural issues may have caused this species to have been under-reported. This highlights that studies making use of Local Ecological Knowledge need to understand the cultural background and context from which data is collected. Nevertheless we recommend our approach, of stratified random interviews to establish mean last capture dates, may be an effective methodology for monitoring freshwater fish species of conservation concern within artisanal fisheries. If fishing effort remains relatively constant, or if changes in fishing effort are accounted for, differences over time in mean last capture dates are likely to represent changes in the status of species. We plan to repeat our interview surveys within the waterscape as part of a long-term fish-monitoring program.
Southeast Asia, a region supporting more threatened species than any other comparable continental area, is in the midst of a conservation crisis. Hunting constitutes the greatest current threat to ...the region’s threatened vertebrates and has resulted in many areas of largely intact forest losing much of their former vertebrate diversity and abundance. Though numerous hunting methods are used, capture with home-made snares is a major driver of this defaunation. Snares are cheaply constructed and easy to set but can be difficult to detect and are highly damaging to vertebrate populations due to their indiscriminate and wasteful nature. The primary response to snaring is the removal of snares by patrol teams: more than 200,000 snares were removed from just five of the region’s protected areas between 2010 and 2015. However due to the low opportunity costs of replacing snares, removal alone is largely ineffective. Without the proactive search, arrest and prosecution of snare-setters, along with incentives not to hunt, snares will continue to be replaced. Legislative reform that criminalises the possession of snares, and the materials used for their construction, inside and immediately adjacent to protected areas is also required. Consistent enforcement of such legislation is essential. This must be combined with longer-term demand reduction activities aimed at changing cultural attitudes and behaviors related to the consumption of wildlife products in Southeast Asia.
We statistically evaluated the relative orientation between gas column density structures, inferred from Herschel submillimetre observations, and the magnetic field projected on the plane of sky, ...inferred from polarized thermal emission of Galactic dust observed by the Balloon-borne Large-Aperture Submillimetre Telescope for Polarimetry (BLASTPol) at 250, 350, and 500 μm, towards the Vela C molecular complex. First, we find very good agreement between the polarization orientations in the three wavelength-bands, suggesting that, at the considered common angular resolution of 3.́0 that corresponds to a physical scale of approximately 0.61 pc, the inferred magnetic field orientation is not significantly affected by temperature or dust grain alignment effects. Second, we find that the relative orientation between gas column density structures and the magnetic field changes progressively with increasing gas column density, from mostly parallel or having no preferred orientation at low column densities to mostly perpendicular at the highest column densities. This observation is in agreement with previous studies by the Planck collaboration towards more nearby molecular clouds. Finally, we find a correspondencebetween (a) the trends in relative orientation between the column density structures and the projected magnetic field; and (b) the shape of the column density probability distribution functions (PDFs). In the sub-regions of Vela C dominated by one clear filamentary structure, or “ridges”, where the high-column density tails of the PDFs are flatter, we find a sharp transition from preferentially parallel or having no preferred relative orientation at low column densities to preferentially perpendicular at highest column densities. In the sub-regions of Vela C dominated by several filamentary structures with multiple orientations, or “nests”, where the maximum values of the column density are smaller than in the ridge-like sub-regions and the high-column density tails of the PDFs are steeper, such a transition is also present, but it is clearly less sharp than in the ridge-like sub-regions. Both of these results suggest that the magnetic field is dynamically important for the formation of density structures in this region.
THE STRUCTURE OF THE LOCAL HOT BUBBLE Liu, W.; Chiao, M.; Collier, M. R. ...
The Astrophysical journal,
01/2017, Letnik:
834, Številka:
1
Journal Article
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ABSTRACT Diffuse X-rays from the Local Galaxy (DXL) is a sounding rocket mission designed to quantify and characterize the contribution of Solar Wind Charge eXchange (SWCX) to the Diffuse X-ray ...Background and study the properties of the Local Hot Bubble (LHB). Based on the results from the DXL mission, we quantified and removed the contribution of SWCX to the diffuse X-ray background measured by the ROSAT All Sky Survey. The "cleaned" maps were used to investigate the physical properties of the LHB. Assuming thermal ionization equilibrium, we measured a highly uniform temperature distributed around kT = 0.097 keV 0.013 keV (FWHM) 0.006 keV (systematic). We also generated a thermal emission measure map and used it to characterize the three-dimensional (3D) structure of the LHB, which we found to be in good agreement with the structure of the local cavity measured from dust and gas.
The representation of the nitrogen (N) cycle in Earth system models (ESMs) is strongly motivated by the constraint N poses on the sequestration of anthropogenic carbon (C). Models typically implement ...a stoichiometric relationship between C and N in which external supply and assimilation by organisms are adjusted to maintain their internal stoichiometry. N limitation of primary productivity thus occurs if the N supply from uptake and fixation cannot keep up with the construction of tissues allowed by C assimilation. This basic approach, however, presents considerable challenges in how to faithfully represent N limitation. Here, we review how N limitation is currently implemented and evaluated in ESMs and highlight challenges and opportunities in their future development. At or near steady state, N limitation is governed by the magnitude of losses from the plant‐unavailable pool vs. N fixation and there are considerable differences in how models treat both processes. In nonsteady‐state systems, the accumulation of N in pools with slow turnover rates reduces N available for plant uptake and can be challenging to represent when initializing ESM simulations. Transactional N limitation occurs when N is incorporated into various vegetation and soil pools and becomes available to plants only after it is mineralized, the dynamics of which depends on how ESMs represent decomposition processes in soils. Other challenges for ESMs emerge when considering seasonal to interannual climatic oscillations as they create asynchronies between C and N demand, leading to transient alternations between N surplus and deficit. Proper evaluation of N dynamics in ESMs requires conceptual understanding of the main levers that trigger N limitation, and we highlight key measurements and observations that can help constrain these levers. Two of the biggest challenges are the mechanistic representation of plant controls on N availability and turnover, including N fixation and organic matter decomposition processes.
An endocrine-disrupting chemical (EDC) is an exogenous chemical, or mixture of chemicals, that can interfere with any aspect of hormone action. The potential for deleterious effects of EDC must be ...considered relative to the regulation of hormone synthesis, secretion, and actions and the variability in regulation of these events across the life cycle. The developmental age at which EDC exposures occur is a critical consideration in understanding their effects. Because endocrine systems exhibit tissue-, cell-, and receptor-specific actions during the life cycle, EDC can produce complex, mosaic effects. This complexity causes difficulty when a static approach to toxicity through endocrine mechanisms driven by rigid guidelines is used to identify EDC and manage risk to human and wildlife populations. We propose that principles taken from fundamental endocrinology be employed to identify EDC and manage their risk to exposed populations. We emphasize the importance of developmental stage and, in particular, the realization that exposure to a presumptive “safe” dose of chemical may impact a life stage when there is normally no endogenous hormone exposure, thereby underscoring the potential for very low-dose EDC exposures to have potent and irreversible effects. Finally, with regard to the current program designed to detect putative EDC, namely, the Endocrine Disruptor Screening Program, we offer recommendations for strengthening this program through the incorporation of basic endocrine principles to promote further understanding of complex EDC effects, especially due to developmental exposures.
Abstract
We describe the selection of galaxies targeted in eight low-redshift clusters (APMCC0917, A168, A4038, EDCC442, A3880, A2399, A119 and A85; 0.029 < z < 0.058) as part of the Sydney-AAO ...Multi-Object Integral field spectrograph Galaxy Survey (SAMI-GS). We have conducted a redshift survey of these clusters using the AAOmega multi-object spectrograph on the 3.9-m Anglo-Australian Telescope. The redshift survey is used to determine cluster membership and to characterize the dynamical properties of the clusters. In combination with existing data, the survey resulted in 21 257 reliable redshift measurements and 2899 confirmed cluster member galaxies. Our redshift catalogue has a high spectroscopic completeness (∼94 per cent) for rpetro ≤ 19.4 and cluster-centric distances R < 2R200. We use the confirmed cluster member positions and redshifts to determine cluster velocity dispersion, R200, virial and caustic masses, as well as cluster structure. The clusters have virial masses 14.25 ≤ log(M200/M⊙) ≤ 15.19. The cluster sample exhibits a range of dynamical states, from relatively relaxed-appearing systems, to clusters with strong indications of merger-related substructure. Aperture- and point spread function matched photometry are derived from Sloan Digital Sky Survey and VLT Survey Telescope/ATLAS imaging and used to estimate stellar masses. These estimates, in combination with the redshifts, are used to define the input target catalogue for the cluster portion of the SAMI-GS. The primary SAMI-GS cluster targets have R <R200, velocities |vpec| < 3.5σ200 and stellar masses $9.5 \le {\rm log({\it M}}^*_{{\rm approx}}/$M⊙)≤12. Finally, we give an update on the SAMI-GS progress for the cluster regions.
There is a need for novel approaches to control pathologies with overexuberant inflammatory reactions. Targeting melanocortin (MC) receptors represents a promising therapy for obesity and chronic ...inflammation, but lack of selectivity and safety concerns limit development. A new way to increase selectivity of biological effects entails the identification of biased agonists. In this study, we characterize the small molecule AP1189 as a biased agonist at receptors MC1 and MC3. Although not provoking canonical cAMP generation, AP1189 addition to MC1 or MC3, but not empty vector, transfected HEK293 cells caused ERK1/2 phosphorylation, a signaling responsible for the proefferocytic effect evoked in mouse primary macrophages. Added to macrophage cultures, AP1189 reduced cytokine release, an effect reliant on both MC1 and MC3 as evident from the use of Mc1r(-/-) and Mc3r(-/-) macrophages. No melanogenesis was induced by AP1189 in B16-F10 melanocytes. In vivo, oral AP1189 elicited anti-inflammatory actions in peritonitis and, upon administration at the peak of inflammation, accelerated the resolution phase by ∼3-fold. Finally, given the clinical efficacy of adrenocorticotropin in joint diseases, AP1189 was tested in experimental inflammatory arthritis, where this biased agonist afforded significant reduction of macroscopic and histological parameters of joint disruption. These proof-of-concept analyses with AP1189, an active oral anti-inflammatory and resolution-promoting compound, indicate that biased agonism at MC receptors is an innovative, viable approach to yield novel anti-inflammatory molecules endowed with a more favorable safety profile.
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