Using stochastically-generated subcolumns to represent cloud structure in a large-scale model

A new method for representing subgrid-scale cloud structure, in which each model column is decomposed into a set of subcolumns, has been introduced into the Geophysical Fluid Dynamics Laboratory's global climate model AM2. Each subcolumn in the decomposition is homogeneous but the ensemble reproduces the initial profiles of cloud properties including cloud fraction, internal variability (if any) in cloud condensate, and arbitrary overlap assumptions that describe vertical correlations. These subcolumns are used in radiation and diagnostic calculations, and have allowed the introduction of more realistic overlap assumptions. This paper describes the impact of these new methods for representing cloud structure in instantaneous calculations and long-term integrations. Shortwave radiation computed using subcolumns and the random overlap assumption differs in the global annual average by more than 4 W/m{sup 2} from the operational radiation scheme in instantaneous calculations; much of this difference is counteracted by a change in the overlap assumption to one in which overlap varies continuously with the separation distance between layers. Internal variability in cloud condensate, diagnosed from the mean condensate amount and cloud fraction, has about the same effect on radiative fluxes as does the ad hoc tuning accounting for this effect in the operational radiation scheme. Long simulations with the new model configuration show little difference from the operational model configuration, while statistical tests indicate that the model does not respond systematically to the sampling noise introduced by the approximate radiative transfer techniques introduced to work with the subcolumns

Anemia prevalence and etiology among women, men, and children in Ethiopia: a study protocol for a national population-based survey.

BACKGROUND: Anemia remains a public health challenge in Ethiopia, affecting an estimated 56% of children under age 5 years, 23% of women of reproductive age and 18% of adult men. However, anemia etiology and the relative contribution of underlying risk factors for anemia remains unclear and has hindered implementation of anemia control programs. METHODS/DESIGN: Anemia Etiology in Ethiopia (AnemEE) is a population-based cross-sectional survey of six regions of Ethiopia that includes children, women of reproductive age, and men from regionally representative households. The survey will include detailed assessment of anemia, iron, inflammatory and nutritional biomarkers, diet, comorbidities, and other factors. The objectives of AnemEE are 1) to generate evidence for decision-making on the etiology of anemia in Ethiopia among men, women and children and 2) to simulate the potential effect of iron fortification and other interventions on the prevalence of anemia and risk of iron overload. DISCUSSION: AnemEE will provide the most comprehensive evaluation of anemia etiology in Ethiopia to date due to its detailed assessment of diet, biomarkers, infections and other risk factors in a population-based sample. By generating evidence and simulating potential interventions, AnemEE will inform the development of high-impact anemia control programs and policies. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04002466 . Registered on 28 June 2019. Retrospectively registered

Tetraspanin CD151 plays a key role in skin squamous cell carcinoma

Here we provide the first evidence that tetraspanin CD151 can support de novo carcinogenesis. During two-stage mouse skin chemical carcinogenesis, CD151 reduces tumor lag time and increases incidence, multiplicity, size, and progression to malignant squamous cell carcinoma (SCC), while supporting both cell survival during tumor initiation and cell proliferation during the promotion phase. In human skin SCC, CD151 expression is selectively elevated compared to other skin cancer types. CD151 support of keratinocyte survival and proliferation may depend on activation of transcription factor STAT3, a regulator of cell proliferation and apoptosis. CD151 also supports PKCα-α6β4 integrin association and PKC-dependent β4 S1424 phosphorylation, while regulating α6β4 distribution. CD151-PKCα effects on integrin β4 phosphorylation and subcellular localization are consistent with epithelial disruption to a less polarized, more invasive state. CD151 ablation, while minimally affecting normal cell and normal mouse functions, markedly sensitized mouse skin and epidermoid cells to chemicals/drugs including DMBA (mutagen) and camptothecin (topoisomerase inhibitor), as well as to agents targeting EGFR, PKC, Jak2/Tyk2, and STAT3. Hence, CD151 ‘co-targeting’ may be therapeutically beneficial. These findings not only support CD151 as a potential tumor target, but also should apply to other cancers utilizing CD151-laminin-binding integrin complexes

Gas-phase metallicity gradients of TNG50 star-forming galaxies

We present the radial gas-phase, mass-weighted metallicity profiles and gradients of the TNG50 star-forming galaxy population measured at redshifts z = 0-3. We investigate the redshift evolution of gradients and examine relations between gradient (negative) steepness and galaxy properties. We find that TNG50 gradients are predominantly negative at all redshifts, although we observe significant diversity among these negative gradients. We determine that the gradients of all galaxies grow more negative with redshift at a roughly constant rate of approximately -0.02 dex kpc-1/Δz. This rate does not vary significantly with galaxy mass. We observe a weak negative correlation between gradient (negative) steepness and galaxy stellar mass at z < 2. However, when we normalize gradients by a characteristic radius defined by the galactic star formation distribution, we find that these normalized gradients do not vary significantly with either stellar mass or redshift. We place our results in the context of previous simulations and show that TNG50 high-redshift gradients are more negative than those of models featuring burstier feedback, which may further highlight high-redshift gradients as important discriminators of galaxy formation models. We also find that z = 0 and z = 0.5 TNG50 gradients are consistent with the gradients observed in galaxies at these redshifts, although the preference for flat gradients observed in redshift z ≥ 1 galaxies is not present in TNG50. If future JWST (James Webb Space Telescope) and ELT (Extremely Large Telescope) observations validate these flat gradients, it may indicate a need for simulation models to implement more powerful radial gas mixing within the ISM (interstellar medium), possibly via turbulence and/or stronger winds

Household-level double burden of malnutrition in Ethiopia: a comparison of Addis Ababa and the rural district of Kersa.

OBJECTIVE: To examine the prevalence of and factors associated with different forms of household-level double burden of malnutrition (DBM) in Ethiopia. DESIGN: We defined DBM using anthropometric measures for adult overweight (BMI ≥ 25 kg/m2), child stunting (height-for-age Z-score <-2 sd) and overweight (weight-for-height Z-score ≥2 sd). We considered sixteen biological, environmental, behavioural and socio-demographic factors. Their association with DBM forms was assessed using generalised linear models. SETTING: We used data from two cross-sectional studies in an urban (Addis Ababa, January-February 2018), and rural setting (Kersa District, June-September 2019). PARTICIPANTS: Five hundred ninety-two urban and 862 rural households with an adult man, adult woman and child <5 years. RESULTS: In Addis Ababa, overweight adult and stunted child was the most prevalent DBM form (9 % (95 % CI 7, 12)). Duration of residence in Addis Ababa (adjusted OR (aOR) 1·03 (95 % CI 1·00, 1·06)), Orthodox Christianity (aOR 1·97 (95 % CI 1·01, 3·85)) and household size (aOR 1·24 (95 % CI 1·01, 1·54)) were associated factors. In Kersa, concurrent child overweight and stunting was the most prevalent DBM form (11 % (95 % CI 9, 14)). Housing quality (aOR 0·33 (95 % CI 0·20, 0·53)), household wealth (aOR 1·92 (95 % CI 1·18, 3·11) and sanitation (aOR 2·08 (95 % CI 1·07, 4·04)) were associated factors. After adjusting for multiple comparisons, only housing quality remained a significant factor. CONCLUSIONS: DBM prevalence was low among urban and rural Ethiopian households. Environmental, socio-economic and demographic factors emerged as potential associated factors. However, we observed no common associated factors among urban and rural households

Attenuated total reflection-FT-IR spectroscopic imaging of protein crystallization

Protein crystallization is of strategic and commercial relevance in the post-genomic era because of its pivotal role in structural proteomics projects. Although protein structures are crucial for understanding the function of proteins and to the success of rational drug design and other biotechnology applications, obtaining high quality crystals is a major bottleneck to progress. The major means of obtaining crystals is by massive-scale screening of a target protein solution with numerous crystallizing agents. However, when crystals appear in these screens, one cannot easily know if they are crystals of protein, salt, or any other molecule that happens to be present in the trials. We present here a method based on Attenuated Total Reflection (ATR)-FT-IR imaging that reliably identifies protein crystals through a combination of chemical specificity and the visualizing capability of this approach, thus solving a major hurdle in protein crystallization. ATR-FT-IR imaging was successfully applied to study the crystallization of thaumatin and lysozyme in a high-throughput manner, simultaneously from six different solutions. This approach is fast as it studies protein crystallization in situ and provides an opportunity to examine many different samples under a range of conditions

Tetraspanin CD151 is a novel prognostic marker in poor outcome endometrial cancer

BACKGROUND: Type II cancers account for 10% of endometrial cancers but 50% of recurrence. Response rates to chemotherapy at recurrence are poor and better prognostic markers are needed to guide therapy. CD151 is a small transmembrane protein that regulates cell migration and facilitates cancer metastasis. High CD151 expression confers poor prognosis in breast, pancreatic and colorectal cancer. The prognostic significance of tetraspanin CD151 expression in poor outcome endometrial cancers was evaluated, along with oestrogen receptor (ER), progesterone receptor (PR), p53, human epidermal growth factor receptor -2 (HER-2), and CD 151 staining compared with α6β1, α3β1 integrins, and E-cadherin. METHODS: Tissue microarray constructed from 156 poor outcome endometrial cancers, tested with immunohistochemistry and staining correlated with clinicopathological data were used. A total of 131 data sets were complete for analysis. RESULTS: Expression of CD151 was significantly higher in uterine papillary serous and clear cell carcinoma than in grade 3 endometrioid carcinoma, sarcoma or carcinosarcoma (P<0.001). In univariate analysis, age, stage, histology type and CD151 were significant for both recurrence free (RFS) and disease specific survival (DSS). In multivariate analyses, CD151 was significant for RFS and DSS (P=0.036 and 0.033, respectively) in triple negative (ER, PR and HER-2 negative) tumours (88/131). The HER-2, p53, ER and PR were not prognostic for survival. There was strong concordance of CD151 with E-cadherin (98%), but not with α6β1 (35%), α3β1 staining (60%). CONCLUSION: The CD151 is a novel marker in type 2 cancers that can guide therapeutic decisions. CD151 may have an important role in tumourigenesis in some histology types

The Sloan Digital Sky Survey Reverberation Mapping Project : systematic investigations of short-timescale CIV broad absorption line variability

We systematically investigate short-timescale (<10-day rest-frame) Civ broad absorption-line (BAL) variability to constrain quasar-wind properties and provide insights into BAL-variability mechanisms in quasars. We employ data taken by the Sloan Digital Sky Survey Reverberation Mapping (SDSS-RM) project, as the rapid cadence of these observations provides a novel opportunity to probe BAL variability on shorter rest-frame timescales than have previously been explored. In a sample of 27 quasars with a median of 58 spectral epochs per quasar, we have identified 15 quasars (55+18−14%), 19 of37 Civ BAL troughs (51+15−12%), and 54 of 1460 epoch pairs (3.7±0.5%) that exhibit significant CivBAL equivalent-width variability on timescales of less than 10 days in the quasar rest frame. These frequencies indicate that such variability is common among quasars and BALs, though somewhat rare among epoch pairs. Thus, models describing BALs and their behavior must account for variability on timescales down to less than a day in the quasar rest frame. We also examine a variety of spectral characteristics and find that in some cases, BAL variability is best described by ionization-state changes, while other cases are more consistent with changes in covering fraction or column density. We adopt a simple model to constrain the density and radial distance of two outflows appearing to vary by ionization-state changes, yielding outflow density lower limits consistent with previous work.PostprintPeer reviewe

Structural Basis for Certain Naturally Occurring Bioflavonoids to Function as Reducing Co-Substrates of Cyclooxygenase I and II

Recent studies showed that some of the dietary bioflavonoids can strongly stimulate the catalytic activity of cyclooxygenase (COX) I and II in vitro and in vivo, presumably by facilitating enzyme re-activation. In this study, we sought to understand the structural basis of COX activation by these dietary compounds.A combination of molecular modeling studies, biochemical analysis and site-directed mutagenesis assay was used as research tools. Three-dimensional quantitative structure-activity relationship analysis (QSAR/CoMFA) predicted that the ability of bioflavonoids to activate COX I and II depends heavily on their B-ring structure, a moiety known to be associated with strong antioxidant ability. Using the homology modeling and docking approaches, we identified the peroxidase active site of COX I and II as the binding site for bioflavonoids. Upon binding to this site, bioflavonoid can directly interact with hematin of the COX enzyme and facilitate the electron transfer from bioflavonoid to hematin. The docking results were verified by biochemical analysis, which reveals that when the cyclooxygenase activity of COXs is inhibited by covalent modification, myricetin can still stimulate the conversion of PGG(2) to PGE(2), a reaction selectively catalyzed by the peroxidase activity. Using the site-directed mutagenesis analysis, we confirmed that Q189 at the peroxidase site of COX II is essential for bioflavonoids to bind and re-activate its catalytic activity.These findings provide the structural basis for bioflavonoids to function as high-affinity reducing co-substrates of COXs through binding to the peroxidase active site, facilitating electron transfer and enzyme re-activation