Pharmacological levels of withaferin A (Withania somnifera) trigger clinically relevant anticancer effects specific to triple negative breast cancer cells

Withaferin A (WA) isolated from Withania somnifera (Ashwagandha) has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN) did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8), cell adhesion molecules (integrins, laminins), pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R) and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1). In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors in therapy-resistant triple negative breast cancer, WA-based therapeutic strategies targeting the uPA pathway hold promise for further (pre)clinical development to defeat aggressive metastatic breast cancer

Bridging Alone: Religious Conservatism, Marital Homogamy, and Voluntary Association Membership

This study characterizes social insularity of religiously conservative American married couples by examining patterns of voluntary associationmembership. Constructing a dataset of 3938 marital dyads from the second wave of the National Survey of Families and Households, the author investigates whether conservative religious homogamy encourages membership in religious voluntary groups and discourages membership in secular voluntary groups. Results indicate that couples’ shared affiliation with conservative denominations, paired with beliefs in biblical authority and inerrancy, increases the likelihood of religious group membership for husbands and wives and reduces the likelihood of secular group membership for wives, but not for husbands. The social insularity of conservative religious groups appears to be reinforced by homogamy—particularly by wives who share faith with husbands

Radio Continuum and Methanol Observations of DR21(OH)

We report high sensitivity sub-arcsecond angular resolution observations of the massive star forming region DR21(OH) at 3.6, 1.3, and 0.7 cm obtained with the Very Large Array. In addition, we conducted observations of CH3OH 44 GHz masers. We detected more than 30 new maser components in the DR21(OH) region. Most of the masers appear to trace a sequence of bow-shocks in a bipolar outflow. The cm continuum observations reveal a cluster of radio sources; the strongest emission is found toward the molecular core MM1. The radio sources in MM1 are located about 5" north of the symmetry center of the CH3OH outflow, and therefore, they are unlikely to be associated with the outflow. Instead, the driving source of the outflow is likely located in the MM2 core. Although based on circumstantial evidence, the radio continuum from MM1 appears to trace free-free emission from shock-ionized gas in a jet. The orientation of the putative jet in MM1 is approximately parallel to the CH3OH outflow and almost perpendicular to the large scale molecular filament that connects DR21 and DR21(OH). This suggests that the (accretion) disks associated with the outflows/jets in the DR21 - DR21(OH) region have symmetry axes mostly perpendicular to the filament.Comment: 26 pages, 6 figures. Accepted for publication in the Astrophysical Journa

Theoretical analysis of nucleation and growth of ZnO nanostructures in vapour phase transport growth

This paper discusses the growth atmosphere, condensing species and nucleation conditions relevant to vapour phase transport growth of ZnO nanostructures, including the molecular parameters and thermodynamics of the gas phase ZnO molecule and its importance compared to atomic Zn and molecular O2. The partial pressure of molecular ZnO in a Zn/O2 mix at normal ZnO growth temperatures is 6x10^-7 of the Zn partial pressures. In typical vapour phase transport growth conditions, using carbothermal reduction, the Zn vapour is always undersaturated while the ZnO vapour is always supersaturated. In the case of the ZnO vapour, our analysis suggests that the barrier to homogeneous nucleation (or heterogeneous nucleation at unseeded/uncatalysed areas of the substrates) is too large for nucleation of this species to take place, which is consistent with experimental evidence that nanostructures will not grow on unseeded areas of substrates. In the presence of suitable accommodation sites, due to ZnO seeds, growth can occur via Zn vapour condensation (followed by oxidation) and via direct condensation of molecular ZnO (whose flux at the surface, although less than that of Zn vapour, is still sufficient to yield an appreciable nanostructure deposit). The balance between these two condensing species is likely to be a sensitive function of growth parameters and could explain both the diversity of reported nanostructure morphologies and the challenges to be faced in developing reproducible and scalable growth systems for specific applicable morphologies

Core-collapse explosions of Wolf-Rayet stars and the connection to type IIb/Ib/Ic supernovae

We present non-LTE time-dependent radiative-transfer simulations of supernova (SN) IIb/Ib/Ic spectra and light curves, based on ~1B-energy piston-driven ejecta, with and without 56Ni, produced from single and binary Wolf-Rayet (W-R) stars evolved at solar and sub-solar metallicities. Our bolometric light curves show a 10-day long post-breakout plateau with a luminosity of 1-5x10^7Lsun. In our 56Ni-rich models, with ~3Msun ejecta masses, this plateau precedes a 20-30-day long re-brightening phase initiated by the outward-diffusing heat wave powered by radioactive decay at depth. In low ejecta-mass models with moderate mixing, Gamma-ray leakage starts as early as ~50d after explosion and causes the nebular luminosity to steeply decline by ~0.02mag/d. Such signatures, which are observed in standard SNe IIb/Ib/Ic, are consistent with low-mass progenitors derived from a binary-star population. We propose that the majority of stars with an initial mass ~<20Msun yield SNe II-P if 'effectively" single, SNe IIb/Ib/Ic if part of a close binary system, and SN-less black holes if more massive. Our ejecta, with outer hydrogen mass fractions as low as ~>0.01 and a total hydrogen mass of ~>0.001Msun, yield the characteristic SN IIb spectral morphology at early times. However, by ~15d after the explosion, only Halpha may remain as a weak absorption feature. Our binary models, characterised by helium surface mass fractions of ~>0.85, systematically show HeI lines during the post-breakout plateau, irrespective of the 56Ni abundance. Synthetic spectra show a strong sensitivity to metallicity, which offers the possibility to constrain it directly from SN spectroscopic modelling.Comment: 23 pages, 2 tables, 13 figures, accepted to MNRA

Low Temperature Waste Immobilization Testing Vol. I

The Pacific Northwest National Laboratory (PNNL) is evaluating low-temperature technologies to immobilize mixed radioactive and hazardous waste. Three waste forms—alkali-aluminosilicate hydroceramic cement, “Ceramicrete” phosphate-bonded ceramic, and “DuraLith” alkali-aluminosilicate geopolymer—were selected through a competitive solicitation for fabrication and characterization of waste-form properties. The three contractors prepared their respective waste forms using simulants of a Hanford secondary waste and Idaho sodium bearing waste provided by PNNL and characterized their waste forms with respect to the Toxicity Characteristic Leaching Procedure (TCLP) and compressive strength. The contractors sent specimens to PNNL, and PNNL then conducted durability (American National Standards Institute/American Nuclear Society [ANSI/ANS] 16.1 Leachability Index [LI] and modified Product Consistency Test [PCT]) and compressive strength testing (both irradiated and as-received samples). This report presents the results of these characterization tests

Successful medical management of emphysematous gastritis with concomitant portal venous air: a case report

<p>Abstract</p> <p>Introduction</p> <p>The causes of diffuse abdominal pain following pelvic surgery are numerous. We present a rare case of acute abdominal pain in a woman in the post-partum period.</p> <p>Case presentation</p> <p>A 25-year-old Caucasian woman with neurofibromatosis type 1 presented to our hospital with diffuse abdominal pain immediately after a cesarean section. The patient was acutely ill and toxic with a fever of 38.8°C, a pulse of 120 beats per minute and a distended abdomen with absent bowel sounds. A computed tomography scan showed air in the wall of the stomach and portal venous system. The patient was successfully treated with intravenous antibiotics, bowel rest and total parenteral nutrition.</p> <p>Conclusion</p> <p>It is rare for a case of emphysematous gastritis associated with portal venous air to be treated successfully without surgery. To the best of our knowledge, to date there has been no reported association of emphysematous gastritis with neurofibromatosis.</p

A tree-based decision model to support prediction of the severity of asthma exacerbations in children

This paper describes the development of a tree-based decision model to predict the severity of pediatric asthma exacerbations in the emergency department (ED) at 2 h following triage. The model was constructed from retrospective patient data abstracted from the ED charts. The original data was preprocessed to eliminate questionable patient records and to normalize values of age-dependent clinical attributes. The model uses attributes routinely collected in the ED and provides predictions even for incomplete observations. Its performance was verified on independent validating data (split-sample validation) where it demonstrated AUC (area under ROC curve) of 0.83, sensitivity of 84%, specificity of 71% and the Brier score of 0.18. The model is intended to supplement an asthma clinical practice guideline, however, it can be also used as a stand-alone decision tool