JOHN MILTON's oft-analysed sonnet 19 has primarily been read autobiographically, exploring ways in which Milton uses Jesus' parable of the talents to explore anxieties about fulfilling his poetic ...vocation with his degenerated vision around 1651.1 Most recently, Margaret Thickstun has re-situated the poem within the genre of devotional lyric, citing the contemporary feature of the intrusive voice. The author argues that the intrusive, preventing voice of patience in Sonnet 19 belongs in a sense to the apostolic church father Clement of Rome. Milton borrows from and poetically translates a section of Clement's letter to the Corinthians for the theological argument of his poem. In the most common reading of the poem, the speaker stands in for Milton as he wrestles with the fact of blindness and an unfulfilled sense of vocation.
To assess the use of brachytherapy (BT) with or without external beam radiation (EBRT) in inoperable stage I endometrial adenocarcinoma in the United States and to determine the effect of BT on ...overall survival (OS) and cause-specific survival (CSS).
Data between 1998 and 2011 from the National Cancer Institute's Surveillance, Epidemiology and End Results database were analyzed. Coarsened exact matching was used to adjust for differences in age and grade between patients who received BT and those who did not. Prognostic factors affecting OS and CSS were evaluated using the Kaplan-Meier product-limit method and a Cox proportional hazards regression model.
A total of 460 patients with inoperable stage I endometrial adenocarcinoma treated with radiation therapy were identified. Radiation consisted of either EBRT (n=260) or BT with or without EBRT (n=200). The only factor associated with BT use was younger patient age (median age, 72 vs 76 years, P=.001). Patients who received BT had a higher 3-year OS (60% vs 47%, P<.001) and CSS (82% vs 74%, P=.032) compared with those who did not. On multivariate analysis, BT use was independently associated with an improved OS (hazard ratio HR 0.67, 95% confidence interval CI 0.52-0.87) and CSS (HR 0.61, 95% CI 0.39-0.93). When patients were matched on age, BT use remained significant on multivariate analysis for OS (HR 0.65, 95% CI 0.48-0.87) and CSS (HR 0.52, 95% CI 0.31-0.84). When matched on age and grade, BT remained independently associated with improved OS and CSS (OS HR 0.62, 95% CI 0.46-0.83; CSS HR 0.57, 95% CI 0.34-0.92).
Brachytherapy is independently associated with improved OS and CSS. It should be considered as part of the treatment regimen for stage I inoperable endometrial cancer patients undergoing radiation.
Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are an invaluable tool for both basic and translational cardiovascular research. The potential that these cells hold for ...therapy, disease modeling and drug discovery is hampered by several bottlenecks that currently limit both the yield and the efficiency of cardiac induction. Here, we present a complete workflow for the production of ready-to-use hiPSC-CMs in a dynamic suspension bioreactor. This includes the efficient and highly reproducible differentiation of hiPSCs into cardiospheres, which display enhanced physiological maturation compared to static 3D induction in hanging drops, and a novel papain-based dissociation method that offers higher yield and viability than the broadly used dissociation reagents TrypLE and Accutase. Molecular and functional analyses of the cardiomyocytes reseeded after dissociation confirmed both the identity and the functionality of the cells, which can be used in downstream applications, either as monolayers or spheroids.
Display omitted
•The BioLevitator supports effective differentiation of cardiospheres from human induced pluripotent stem cells (hiPSCs).•Papain from Carica papaya outperforms broadly-used dissociation reagents in generating single viable cardiomyocytes.•Cardiomyocytes obtained from papain dissociation display molecular and functional characteristics typical of hiPSC-CMs.
Neurogenin 2 encodes a neural-specific transcription factor (NGN2) able to drive neuronal fate on somatic and stem cells. NGN2 is expressed in neural progenitors within the developing central and ...peripheral nervous systems. Overexpression of NGN2 in human induced pluripotent stem cells (hiPSCs) or human embryonic stem cells has been shown to efficiently trigger conversion to neurons. Here we describe two gene-edited hiPSC lines harbouring a doxycycline (DOX)-inducible cassette in the AAVS1 locus driving expression of NGN2 (BIONi010-C-13) or NGN2-T2A-GFP (BIONi010-C-15). By introducing NGN2-expressing cassette, we reduce variability associated with conventional over-expression methods such as viral transduction, making these lines amenable for scale-up production and screening processes. DOX-treated hiPSCs convert to neural phenotype within one week and display the expression of structural neuronal markers such as Beta-III tubulin and tau. We performed functional characterization of NGN2-neurons co-cultured with hiPSC-derived astrocytes in a “fully-humanized” set up. Passive properties of NGN2-neurons were indistinguishable from mouse primary cells while displaying variable activity in extracellular recordings performed in multi-electrode arrays (MEAs). We demonstrate that hiPSC-derived astrocytes and neurons can be co-cultured and display functional properties comparable to the gold standard used in electrophysiology. Both lines are globally available via EBiSC repository at https://cells.ebisc.org/.
The Man Who Wasn't There Fischer, Benjamin B.
International journal of intelligence and counterintelligence,
01/2017, Letnik:
30, Številka:
1
Journal Article
Recenzirano
Paul Stombaugh found himself where no Central Intelligence Agency (CIA) officer ever wanted to be, in an interrogation room in the Lubyanka, the infamous headquarters of the KGB (Committee for State ...Security). The agent Stombaugh was supposed to meet was named Adolf Tolkachev, who claimed to be a senior designer employed at a secret defense facility, the Scientific Research Institute for Radio Engineering, which developed radars for military aircraft. The CIA was determined to tell the Tolkachev tale once again, this time using the skills of a talented and award-winning author. Whether the book is a true story of Cold War espionage and betrayal, as its subtitle asserts, is open to question, however.
We investigated the direct and indirect (residual) antibacterial effects of various concentrations of triple antibiotic paste (TAP) loaded into a methylcellulose system. Enterococcus faecalis (E. ...faecalis) was grown on sterilized dentin blocks (n = 60) and treated with clinically used TAP (1,000 mg/mL), low concentrations of methylcellulose-based TAP (100, 10, and 1 mg/mL), placebo paste, or 1.5% NaOCl (n = 10). The pastes were then removed, and biofilm disruption assays were performed. Additional dentin blocks (n = 120) were pretreated with the same experimental groups (n = 20). The pastes were rinsed off, and the samples were immersed independently in phosphate-buffered saline for 2 and 4 weeks (n = 10). E.faecalis was then grown on the dentin blocks, and biofilm disruption assays were performed. Fisher’s Exact and Wilcoxon rank sum tests were used for statistical analyses. With regard to direct antibacterial effects, all treatment groups demonstrated complete eradication of biofilms in comparison to placebo paste, while 10 mg/mL of TAP or higher provided substantial residual antibacterial effects. However, dentin treated with 1 mg/mL of TAP or 1.5% NaOCl did not provide substantial residual antibacterial effects. Dentin pretreated with 10 mg/mL of TAP or higher exhibited extended residual antibacterial effects and can thus be used during endodontic regeneration.(J Oral Sci 58, 575-582, 2016)
To better understand the small-scale variability of rainfall and its isotopic composition it is advantageous to utilize rain samplers which are at the same time low-cost, low-tech, robust, and ...precise with respect to the collected rainwater isotopic composition. We assessed whether a self-built version of the Kennedy sampler is able to collect rainwater consistently without mixing with antecedent collected water. We called the self-built sampler made from honey jars and silicon tubing the Zurich sequential sampler. Two laboratory experiments show that high rainfall intensities can be sampled and that the volume of water in a water sample originating from a different bottle was generally less than 1 ml. Rainwater was collected in 5 mm increments for stable isotope analysis using three (year 2011) and five (years 2015 and 2016) rain samplers in Zurich (Switzerland) during eleven rainfall events. The standard deviation of the total rainfall amounts between the different rain gauges was <1%. The standard deviation of delta O-18 and delta H-2 among the different sequential sampler bottles filled at the same time was generally <0.3 parts per thousand for delta O-18 and <2 parts per thousand for delta H-2 (8 out of 11 events). Larger standard deviations could be explained by leaking bottle(s) with subsequent mixing of water with different isotopic composition of at least one out of the five samplers. Our assessment shows that low-cost, low-tech rain samplers, when well maintained, can be used to collect sequential samples of rainfall for stable isotope analysis and are therefore suitable to study the spatio-temporal variability of the isotopic composition of rainfall.
Plant protection products (PPPs) consist of one or more active substances and several co-formulants. Active substances provide the functionality of the PPP and are consequently evaluated according to ...standard test methods set by legal data requirements before approval, whereas co-formulants' toxicity is not as comprehensively assessed. However, in some cases mixture effects of active substances and co-formulants might result in increased or different forms of toxicity. In a proof-of-concept study we hence built on previously published results of Zahn et al. (201838) on the mixture toxicity of Priori Xtra
and Adexar
to specifically investigate the influence of co-formulants on the toxicity of these commonly used fungicides. Products, their respective active substances in combination as well as some co-formulants were applied to human hepatoma cell line (HepaRG) in several dilutions. Cell viability analysis, mRNA expression, abundance of xenobiotic metabolizing enzymes and intracellular concentrations of active substances determined by LC-MS/MS analyses demonstrated that the toxicity of the PPPs is influenced by the presence of co-formulants
. PPPs were more cytotoxic than the mix of their active substances. Gene expression profiles of cells treated with the PPPs were similar to those treated with their respective mixture combinations with marked differences. Co-formulants can cause gene expression changes on their own. LC-MS/MS analyses revealed higher intracellular concentrations of active substances in cells treated with PPPs compared to those treated with the respective active substances' mix. Proteomic data showed co-formulants can induce ABC transporters and CYP enzymes. Co-formulants can contribute to the observed increased toxicity of PPPs compared to their active substances in combination due to kinetic interactions, necessitating a more comprehensive evaluation approach.
Tolkachev Evidence Still Skimpy Fischer, Benjamin B.
International journal of intelligence and counterintelligence,
10/2016, Letnik:
29, Številka:
4
Journal Article
Recenzirano
Hoffman says that Tolkachev was convicted of treason on 24 Sep 1985 and executed on 22 Oct 1985. According to the Soviet press, the alleged trial and execution occurred a year later. The Politburo ...document Hoffman cites is suspicious.
PDF
