Tanshindiol C

Numerical stability of the C method and a perturbative preconditioning technique to improve convergence.[Pubmed:29036071]

J Opt Soc Am A Opt Image Sci Vis. 2017 Jun 1;34(6):881-891.

The translational coordinate transformation method (the C method) in grating theory is studied numerically and analytically. We first study the convergence characteristics of the C method by numerical computations in high floating-point data precisions. Guided by insights gained from this numerical study we analytically studied condition numbers of the most important eigenvalues of the eigenvalue problem of the C method. Asymptotic estimates of condition numbers of these eigenvalues and estimates of convergence rate of the error in satisfying the Helmholtz equation by the eigenvectors are derived. These theoretical results explain well many observed numerical phenomena of the C method. Using the first-order perturbation theory of simple eigenvalues we analyze the effects of round-off errors on eigenvalue distribution and condition numbers. This leads to an extremely simple perturbative preconditioning technique that significantly improves the numerical stability of the C method with as little as just one line of code modification. The performance of the perturbatively preconditioned C method is not inferior to the C method preconditioned by the multilinear parameterization technique. We recommend it as the preferred method for modeling deep and smooth gratings.

Speciated Monitoring of Gas-Phase Organic Peroxy Radicals by Chemical Ionization Mass Spectrometry: Cross-Reactions between CH3O2, CH3(CO)O2, (CH3)3CO2, and c-C6H11O2.[Pubmed:29035543]

J Phys Chem A. 2017 Nov 9;121(44):8453-8464.

Organic peroxy radicals ("RO2", with R organic) are key intermediates in most oxygen-rich systems, where organic compounds are oxidized (natural environment, flames, combustion engines, living organisms, etc). But, until recently, techniques able to monitor simultaneously and distinguish between RO2 species ("speciated" detection) have been scarce, which has limited the understanding of complex systems containing these radicals. Mass spectrometry using proton transfer ionization has been shown previously to detect individual gas-phase RO2 separately. In this work, we illustrate its ability to speciate and monitor several RO2 simultaneously by investigating reactions involving CH3O2, CH3C(O)O2, c-C6H11O2, and (CH3)3CO2. The detection sensitivity of each of these radicals was estimated by titration with NO to between 50 and 1000 Hz/ppb, with a factor from 3 to 5 of uncertainties, mostly due to the uncertainties in knowing the amounts of added NO. With this, the RO2 concentration in the reactor was estimated between 1 x 10(10) and 1 x 10(12) molecules cm(-3). When adding a second radical species to the reactor, the kinetics of the cross-reaction could be studied directly from the decay of the first radical. The time-evolution of two and sometimes three different RO2 was followed simultaneously, as the CH3O2 produced in further reaction steps was also detected in some systems. The rate coefficients obtained are (in molecule(-1) cm(3) s(-1)): kCH3O2+CH3C(O)O2 = 1.2 x 10(-11), kCH3O2+t-butylO2 = 3.0 x 10(-15), kc-hexylO2+CH3O2 = 1.2 x 10(-13), kt-butylO2+CH3C(O)O2 = 3.7 x 10(-14), and kc-hexylO2+t-butylO2 = 1.5 x 10(-15). In spite of their good comparison with the literature and good reproducibility, large uncertainties (x5/5) are recommended on these results because of those in the detection sensitivities. This work is a first illustration of the potential applications of this technique for the investigation of organic radicals in laboratory and in more complex systems.

Nuclear localized C9orf72-associated arginine-containing dipeptides exhibit age-dependent toxicity in C. elegans.[Pubmed:29036691]

Hum Mol Genet. 2017 Dec 15;26(24):4916-4928.

A hexanucleotide repeat expansion mutation in the C9orf72 gene represents a prevalent genetic cause of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Non-canonical translation of this repeat gives rise to several distinct dipeptide protein species that could play pathological roles in disease. Here, we show in the model system Caenorhabditis elegans that expression of the arginine-containing dipeptides, but not alanine-containing dipeptides, produces toxic phenotypes in multiple cellular contexts, including motor neurons. Expression of either (PR)50 or (GR)50 during development caused a highly penetrant developmental arrest, while post-developmental expression caused age-onset paralysis. Both (PR)50- and (GR)50-green fluorescent protein tagged dipeptides were present in the nucleus and nuclear localization was necessary and sufficient for their toxicity. Using an inducible expression system, we discovered that age-onset phenotypes caused by (PR)50 required both continual (PR)50 expression and an aged cellular environment. The toxicity of (PR)50 was modified by genetic mutations that uncouple physiological aging from chronological aging. However, these same mutations failed to modify the toxicity of (GR)50, suggesting that (PR)50 and (GR)50 exert their toxicity through partially distinct mechanism(s). Changing the rate of physiological aging also mitigates toxicity in other C. elegans models of ALS, suggesting that the (PR)50 dipeptide might engage similar toxicity mechanisms as other ALS disease-causing proteins.

Copper-Catalyzed C(sp(2))-S Coupling Reactions for the Synthesis of Aryl Dithiocarbamates with Thiuram Disulfide Reagents.[Pubmed:29035550]

Org Lett. 2017 Nov 3;19(21):5916-5919.

An efficient protocol for the copper-catalyzed preparation of aryl dithiocarbamates from aryl iodides and inexpensive, environmentally benign tetraalkylthiuram disulfides was developed. The features of mild reaction conditions, high yields, and broad substrate scope render this new approach synthetically attractive for the preparation of potentially biologically active compounds.

Systematic review with meta-analysis: performance of dried blood spots for hepatitis C antibodies detection.[Pubmed:29035801]

Public Health. 2017 Dec;153:128-136.

OBJECTIVES: Dried blood spots (DBS) specimens can be used for hepatitis C virus (HCV) infection screening in cases where serum specimens are difficult to obtain. However, uncertainties surround the sensitivity and specificity of DBS for HCV antibodies (anti-HCV) serology testing. We aimed to evaluate the accuracy of DBS use to screen for HCV infection. STUDY DESIGN: We carried out a systematic review and meta-analysis. METHODS: Medline and EMBASE databases were searched for articles published between 1989 and November 2016. We included studies comparing DBS to plasma/serum specimens to detect anti-HCV in adults. Two authors extracted data and assessed the quality of the studies using an adapted standards for reporting diagnostic accuracy studies (STARD) and independently checked the data for accuracy. Meta-analysis was computed with the bivariate and the hierarchical summary receiver-operating characteristic models. RESULTS: Twelve studies (3307 specimens) were analyzed, where 11 of them evaluated the anti-HCV using enzyme immunoassays (EIAs), and the remaining one used rapid diagnostic tests. The studies were mostly case-controls (83.3%) and from developed countries (66.7%). The overall pooled sensitivity (95% confidence interval; CI) and specificity (95% CI) of DBS to detect anti-HCV was 98.1% (96.1-99.1%) and 99.7% (98.9-99.9%), respectively. In studies using EIAs, the pooled sensitivity and specificity were 97.3% (94.3-98.8%) and 99.6% (98.5-99.9%), respectively. Considering only studies using EIAs, sensitivity analysis excluding one study carried out in people who inject drugs showed the pooled sensitivity of 97.8% (96.2-98.8%) and specificity of 99.5% (98.5-99.9%). CONCLUSIONS: In testing for anti-HCV by means of EIAs, the efficacy of DBS is found to be similar or slightly lower than that of serum specimens. However, the risk of finding negative and positive results that are both false when using DBS remains present. Therefore, further work including optimal storage and processing methodologies are recommended. This is to help establish consensus guidelines for use of DBS specimens for anti-HCV screening.