Enhanced sensitivity to Wnts is an emerging hallmark of a subset of cancers, defined in part by mutations regulating the abundance of their receptors. Whether these mutations identify a clinical ...opportunity is an important question. Inhibition of Wnt secretion by blocking an essential post-translational modification, palmitoleation, provides a useful therapeutic intervention. We developed a novel potent, orally available PORCN inhibitor, ETC-1922159 (henceforth called ETC-159) that blocks the secretion and activity of all Wnts. ETC-159 is remarkably effective in treating RSPO-translocation bearing colorectal cancer (CRC) patient-derived xenografts. This is the first example of effective targeted therapy for this subset of CRC. Consistent with a central role of Wnt signaling in regulation of gene expression, inhibition of PORCN in RSPO3-translocated cancers causes a marked remodeling of the transcriptome, with loss of cell cycle, stem cell and proliferation genes, and an increase in differentiation markers. Inhibition of Wnt signaling by PORCN inhibition holds promise as differentiation therapy in genetically defined human cancers.
Context.
Shadows in scattered light images of protoplanetary disks are a common feature and support the presence of warps or misalignments between disk regions. These warps are possibly caused by an ...inclined (sub-)stellar companion embedded in the disk.
Aims.
We aim to study the morphology of the protoplanetary disk around the Herbig Ae star HD 139614 based on the first scattered light observations of this disk, which we model with the radiative transfer code
MCMax3D
.
Methods.
We obtained
J
- and
H
-band observations that show strong azimuthal asymmetries in polarized scattered light with VLT/SPHERE. In the outer disk, beyond ~30 au, a broad shadow spans a range of ~240 deg in position angle, in the east. A bright ring at ~16 au also shows an azimuthally asymmetric brightness, with the faintest side roughly coincidental with the brightest region of the outer disk. Additionally, two arcs are detected at ~34 and ~50 au. We created a simple four-zone approximation to a warped disk model of HD 139614 in order to qualitatively reproduce these features. The location and misalignment of the disk components were constrained from the shape and location of the shadows they cast.
Results.
We find that the shadow on the outer disk covers a range of position angles too wide to be explained by a single inner misaligned component. Our model requires a minimum of two separate misaligned zones – or a continuously warped region – to cast this broad shadow on the outer disk. A small misalignment of ~4° between adjacent components can reproduce most of the observed shadow features.
Conclusions.
Multiple misaligned disk zones, potentially mimicking a warp, can explain the observed broad shadows in the HD 139614 disk. A planetary mass companion in the disk, located on an inclined orbit, could be responsible for such a feature and for the dust-depleted gap responsible for a dip in the SED.
Context. Protoplanetary disks show large diversity regarding their morphology and dust composition. With mid-infrared interferometry the thermal emission of disks can be spatially resolved, and the ...distribution and properties of the dust within can be studied. Aims. Our aim is to perform a statistical analysis on a large sample of 82 disks around low- and intermediate-mass young stars, based on mid-infrared interferometric observations. We intend to study the distribution of disk sizes, variability, and the silicate dust mineralogy. Methods. Archival mid-infrared interferometric data from the MIDI instrument on the Very Large Telescope Interferometer are homogeneously reduced and calibrated. Geometric disk models are used to fit the observations to get spatial information about the disks. An automatic spectral decomposition pipeline is applied to analyze the shape of the silicate feature. Results. We present the resulting data products in the form of an atlas, containing N band correlated and total spectra, visibilities, and differential phases. The majority of our data can be well fitted with a continuous disk model, except for a few objects, where a gapped model gives a better match. From the mid-infrared size–luminosity relation we find that disks around T Tauri stars are generally colder and more extended with respect to the stellar luminosity than disks around Herbig Ae stars. We find that in the innermost part of the disks (r ≲ 1 au) the silicate feature is generally weaker than in the outer parts, suggesting that in the inner parts the dust is substantially more processed. We analyze stellar multiplicity and find that in two systems (AB Aur and HD 72106) data suggest a new companion or asymmetric inner disk structure. We make predictions for the observability of our objects with the upcoming Multi-AperTure mid-Infrared SpectroScopic Experiment (MATISSE) instrument, supporting the practical preparations of future MATISSE observations of T Tauri stars.
Millions of people in Southern Africa are deprived of basic human rights such as the right to education and work because of the large and growing unmet demand for assistive technologies (AT). ...Evidence is needed to better characterize the lack of AT access.
This study serves to identify the sociodemographic factors that are associated with access to AT in two countries in Southern Africa, Botswana and Swaziland. To achieve this aim, logistics regression was applied to a subset of variables from two Living Conditions Studies, nationally representative surveys that were conducted in Southern Africa (2014 and 2010).
In Botswana, 44% of people who needed AT did not receive it, while in Swaziland the unmet need was 67%. Among the sociodemographic variables tested, the type of disability was the most important factor in determining AT access in both countries. The likelihood of AT access was highest in both countries for those who had mobility limitations (i.e., difficulty walking/climbing stairs) Botswana: 6.4 odds ratio (OR) = 6.4., 95% confidence internal (CI) (3.6-11.3); Swaziland: OR = 3.2, CI (1.4-7.3), in comparison to those with non-mobility types of disabilities.
These findings provide support for governments and other stakeholders in the AT sector to prioritize AT to address the large unmet demand, and expand the range of AT products provided so that people with hearing, seeing, self-care, communication and cognition difficulties have equal access to AT as those with mobility impairments. A step toward achieving these aims is to inventory AT product types that are commonly covered through the public sector in each country, and identify common gaps (e.g., daily living aids). Advancing the AT sector as a whole within Southern Africa will require large scale qualitative studies that achieve a comprehensive understanding of the bottlenecks in regional AT supply, procurement, and delivery systems.
A 50 kyr‐long exceptionally well‐dated and highly resolved stalagmite oxygen (δ18O) and carbon (δ13C) isotope record from Sofular Cave in northwestern Turkey helps to further improve the dating of ...Greenland Interstadials (GI) 1, and 3–12. Timing of most GI in the Sofular record is consistent within ±10 to 300 years with the “iconic” Hulu Cave record. Larger divergences (>500 years) between Sofular and Hulu are only observed for GI 4 and 7. The Sofular record differs from the most recent NGRIP chronology by up to several centuries, whereas age offsets do not increase systematically with depth. The Sofular record also reveals a rapid and sensitive climate and ecosystem response in the eastern Mediterranean to GI, whereas a phase lag of ∼100 years between climate and full ecosystem response is evident. Finally, results of spectral analyses of the Sofular isotope records do not support a 1,470‐year pacing of GI.
Microalgae have been considered as one of the most promising biomass feedstocks for various industrial applications such as biofuels, animal/aquaculture feeds, food supplements, nutraceuticals, and ...pharmaceuticals. Several biotechnological challenges associated with algae cultivation, including the small size and negative surface charge of algal cells as well as the dilution of its cultures, need to be circumvented, which increases the cost and labor. Therefore, efficient biomass recovery or harvesting of diverse algal species represents a critical bottleneck for large-scale algal biorefinery process. Among different algae harvesting techniques (e.g., centrifugation, gravity sedimentation, screening, filtration, and air flotation), the flocculation-based processes have acquired much attention due to their promising efficiency and scalability. This review covers the basics and recent research trends of various flocculation techniques, such as auto-flocculation, bio-flocculation, chemical flocculation, particle-based flocculation, and electrochemical flocculation, and also discusses their advantages and disadvantages. The challenges and prospects for the development of eco-friendly and economical algae harvesting processes have also been outlined here.
The source and seasonality of rainfall in southern Arabia during the early‐ to mid‐Holocene and preceding humid periods are controversial because fossil lacustrine sediments provide solely indirect ...information on the amount of rainfall. Hydrogen and oxygen isotope measurements on fluid inclusion water trapped in Holocene and Pleistocene stalagmites from Hoti Cave in Northern Oman are direct indicators of the isotopic composition of paleoprecipitation. Isotope values of fluid inclusions formed during peak interglacial periods plot along monsoonal water lines and are indicative of a southern monsoonal moisture source. The last monsoon‐dominated period lasting from ∼10,100 to 6,300 years before present was terminated within a few decades in southeastern Arabia. The subsequent reduction in rainfall amount and change from predominantly summer to predominantly winter rainfall had a profound impact on human communities living in this area and triggered migration from inland to coastal areas where resources were more abundant.
Plain Language Summary
During the Quaternary period, the Arabian Peninsula experienced short intervals of enhanced rainfall, turning the Arabian Desert into a savannah‐type landscape with abundant lakes and wetlands. These intervals are well‐documented in lake sediments and cave deposits throughout Arabia, whereas the source of rainfall is uncertain. Ancient rainwater trapped in fluid inclusions in stalagmites from Hoti Cave, Northern Oman, allows us to determine moisture source changes over the last 350,000 years before present. Using new analytical methods to extract the water from fluid inclusions and measure its hydrogen and oxygen isotopic composition, we are able to show that greatly enhanced rainfall was caused by an intensification and greater northward extension of the African and Indian monsoons into Arabia. For the last humid period between ∼10,500 and 6,300 years before present, stalagmites from Hoti Cave reveal an abrupt termination of the monsoon‐dominated period, a sharp decline in precipitation and change from a summer‐ to winter‐dominated rainfall regime in southeastern Arabia. As a result, human communities were severely affected by this major climatic change and forced to migrate from inland to coastal areas, where water and resources were more abundant.
Key Points
Hydrogen and oxygen isotopes in fluid inclusions in stalagmites from Hoti Cave, Northern Oman, reveal changes in the source of rainfall
Rainfall during the early and middle Holocene originated from the Indian Ocean and was associated with the Indian summer monsoon
A change in the seasonality and reduction in rainfall at ∼6,300 years before present had a profound impact on communities in Northern Oman
ABSTRACT
The inner regions of protoplanetary discs (from ∼0.1 to 10 au) are the expected birthplace of planets, especially telluric. In those high-temperature regions, solids can experience cyclical ...annealing, vapourisation, and recondensation. Hot and warm dusty grains emit mostly in the infrared domain, notably in N-band (8–13 μm). Studying their fine chemistry through mid-infrared spectro-interferometry with the new Very Large Telescope Interferometer (VLTI) instrument Multi AperTure mid-Infrared SpectroScopic Experiment (MATISSE), which can spatially resolve these regions, requires detailed dust chemistry models. Using radiative transfer, we derived infrared spectra of a fiducial static protoplanetary disc model with different inner-disc (<1 au) dust compositions. The latter were derived from condensation sequences computed at local thermodynamic equilibrium (LTE) for three initial C/O ratios: subsolar (C/O = 0.4), solar (C/O = 0.54), and supersolar (C/O = 1). The three scenarios return very different N-band spectra, especially when considering the presence of sub-micron-sized dust grains. MATISSE should be able to detect these differences and trace the associated sub-au-scale radial changes. We propose a first interpretation of N-band ‘inner-disc’ spectra obtained with the former VLTI instrument MID-infrared Interferometric instrument (MIDI) on three Herbig stars (HD 142527, HD 144432, HD 163296) and one T Tauri star (AS 209). Notably, we could associate a supersolar (‘carbon-rich’) composition for HD 142527 and a subsolar (‘oxygen-rich’) one for HD 1444432. We show that the inner-disc mineralogy can be very specific and not related to the dust composition derived from spatially unresolved mid-infrared spectroscopy. We highlight the need for including more complex chemistry when interpreting solid-state spectroscopic observations of the inner regions of discs, and for considering dynamical aspects for future studies.
► Comparison between Ce(III) and Ce(IV) salts as inhibitors of AA2024 corrosion. ► Both of cerium salts could react as corrosion activators or inhibitors as well. ► Oxides/hydroxides formed during ...inhibition by Ce(III) cover all cathodic sites. ► Ce(III) deposits contain Ce3+ and Ce4+ species but these of Ce(IV) have only Ce3+. ► The inhibition efficiencies of Ce(III) solutions are higher than those of Ce(IV).
The corrosion protection of the AA2024 aluminum alloy in 0.01M NaCl solutions of Ce(III) and Ce(IV) ammonium nitrates was studied. The inhibition efficiency was evaluated applying linear sweep voltammetry (LSV) and electrochemical impedance spectroscopy (EIS). Superficial analytical techniques (optical microscopy, SEM, EDS and XPS) were applied for elucidation of the inhibition mechanism. The results showed that both cerium salts could behave either as inhibitors or activators of the corrosion process depending on the experimental conditions. The solutions of Ce(III) salt revealed better inhibitive ability than those of Ce(IV) in a relatively large range of conditions.
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