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Discover the most talked about and latest scientific content & concepts.

Concept: Limit of a sequence

226

BACKGROUND TO THE DEBATE: Tobacco continues to kill millions of people around the world each year and its use is increasing in some countries, which makes the need for new, creative, and radical efforts to achieve the tobacco control endgame vitally important. One such effort is discussed in this PLOS Medicine Debate, where Simon Chapman presents his proposal for a “smoker’s license” and Jeff Collin argues against. Chapman sets out a case for introducing a smart card license for smokers designed to limit access to tobacco products and encourage cessation. Key elements of the smoker’s license include smokers setting daily limits, financial incentives for permanent license surrender, and a test of health risk knowledge for commencing smokers. Collin argues against the proposal, saying that it would shift focus away from the real vector of the epidemic-the tobacco industry-and that by focusing on individuals it would censure victims, increase stigmatization of smokers, and marginalize the poor.

Concepts: Tobacco, English-language films, Vector space, Proposal, Focusing, Limit, Limit of a sequence, Ryan Reynolds

193

BACKGROUND TO THE DEBATE: Tobacco continues to kill millions of people around the world each year and its use is increasing in some countries, which makes the need for new, creative, and radical efforts to achieve the tobacco control endgame vitally important. One such effort is discussed in this PLOS Medicine Debate, where Simon Chapman presents his proposal for a “smoker’s license” and Jeff Collin argues against. Chapman sets out a case for introducing a smart card license for smokers designed to limit access to tobacco products and encourage cessation. Key elements of the smoker’s license include smokers setting daily limits, financial incentives for permanent license surrender, and a test of health risk knowledge for commencing smokers. Collin argues against the proposal, saying that it would shift focus away from the real vector of the epidemic-the tobacco industry-and that by focusing on individuals it would censure victims, increase stigmatization of smokers, and marginalize the poor.

Concepts: Tobacco, English-language films, Vector space, Proposal, Focusing, Limit, Limit of a sequence, Ryan Reynolds

43

As the cost of sequencing continues to decrease and the amount of sequence data generated grows, new paradigms for data storage and analysis are increasingly important. The relative scaling behavior of these evolving technologies will impact genomics research moving forward.

Concepts: Series, Topology, Sequence, Computer data storage, The Real, Real analysis, Limit of a sequence, Cauchy sequence

27

We report a detailed binding study addressing both the thermodynamics and kinetics of binding of a large set of guest molecules - with widely varying properties - to a water-soluble metal-organic M4L6 host. The effects of different guest properties upon binding strength and kinetics are elucidated by a systematic analysis of the binding data through principal component analysis, thus allowing for structure-property relationships to be determined. These insights allowed us to design more complex encapsulation sequences, in which multiple guests, added simultaneously, are bound and released by the host in a time-dependent manner, thus allowing multiple states of the system to be accessed sequentially. Moreover, by inclusion of the pH-sensitive guest pyridine we were able to further extend our control over binding by creating a reversible pH-controlled three-guest sequential binding cycle.

Concepts: Series, Mathematical analysis, Sequence, Principal component analysis, Natural number, Set, Real analysis, Limit of a sequence

27

In this paper, a high-affinity ssDNA aptamer binding to Salmonella typhimurium was obtained by a whole-bacterium-based Systemic Evolution of Ligands by Exponential Enrichment (SELEX) procedure. After nine rounds of selection with S. typhimurium as the target, a highly enriched oligonucleotide pool was sequenced and then grouped into different families based on primary sequence homology and secondary structure similarity. Eleven sequences from different families were selected for further characterization via flow cytometry analysis. The results showed that the sequence ST2P demonstrates affinity for S. typhimurium much more strongly and specifically than other sequences tested. The estimated K¬d value of this particularly promising aptamer was 6.33 ± 0.58 nM. To demonstrate the potential use of the aptamers in the quantitative determination of S. typhimurium, a fluorescent bioassay with the aptamer ST2P was prepared. Under the optimal conditions, the correlation between the concentration of S. typhimurium and fluorescent signal was found to be linear within the range of 50-106 cfu/mL (R2 =0.9957). The limit of detection (LOD) of the developed method were found to be 25 cfu/mL. Our work demonstrates that this aptamer could potentially be used to improve the detection of S. typhimurium.

Concepts: DNA, Bioinformatics, Evolution, Flow cytometry, Sequence, Salmonella enterica, Aptamer, Limit of a sequence

25

We have suggested a novel approach for classification of flow methods according to the conditions under which the mass transfer processes and chemical reactions take place in the flow mode: dispersion-convection flow methods (1) and forced-convection flow methods (2). The first group includes continuous flow analysis, flow injection analysis, all injection analysis, sequential injection analysis, sequential injection chromatography, cross injection analysis, multicommutated flow analysis, multisyringe flow injection analysis, multi-pumping flow systems, loop flow analysis and simultaneous injection effective mixing flow analysis. The second group includes segmented flow analysis, zone fluidics, flow batch analysis, sequential injection analysis with a mixing chamber, stepwise injection analysis and multicommutated stepwise injection analysis. The offered classification allows to systematize a large number of the flow methods. Recent development and application of dispersion-convection flow methods and forced-convection flow methods are presented. [Figure: see text].

Concepts: Series, Chemical reaction, Chemical substance, According to Jim, Chemical engineering, Limit of a sequence, Mass transfer, AutoAnalyzer

23

The envelope glycoproteins (Envs) of HIV-1 continuously evolve in the host by random mutations and recombination events. The resulting diversity of Env variants circulating in the population and their continuing diversification process limit the efficacy of AIDS vaccines. We examined the historic changes in Env sequence and structural features (measured by integrity of epitopes on the Env trimer) in a geographically defined population in the United States. As expected, many Env features were relatively conserved during the 1980s. From this state, some features diversified whereas others remained conserved across the years. We sought to identify “clues” to predict the observed historic diversification patterns. Comparison of viruses that cocirculate in patients at any given time revealed that each feature of Env (sequence or structural) exists at a defined level of variance. The in-host variance of each feature is highly conserved among individuals but can vary between different HIV-1 clades. We designate this property “volatility” and apply it to model evolution of features as a linear diffusion process that progresses with increasing genetic distance. Volatilities of different features are highly correlated with their divergence in longitudinally monitored patients. Volatilities of features also correlate highly with their population-level diversification. Using volatility indices measured from a small number of patient samples, we accurately predict the population diversity that developed for each feature over the course of 30 years. Amino acid variants that evolved at key antigenic sites are also predicted well. Therefore, small “fluctuations” in feature values measured in isolated patient samples accurately describe their potential for population-level diversification. These tools will likely contribute to the design of population-targeted AIDS vaccines by effectively capturing the diversity of currently circulating strains and addressing properties of variants expected to appear in the future.

Concepts: Immune system, Evolution, Variance, Prediction, Futurology, Future, Probability theory, Limit of a sequence

10

The study aimed for evaluating the diagnostic value of a 2D Turbo Spin Echo (TSE) magnetic resonance (MR) imaging sequence implanted slice-encoding metal artifact correction (SEMAC) and view-angle tilting (VAT) in patients with spinal instrumentation.Sixty-seven consecutive patients with an average age of 59.7 ± 17.8 years old (range: 32-75 years) were enrolled in this study. Both sagittal, axial T1-weighted and T2-weighted MRI images were acquired with a standard TSE sequence and a high-bandwidth TSE sequence implemented the SEMAC and VAT techniques. Three continuous sections around the instrumentation in axial and sagittal images were selected for quantitative evaluation. The measurement included cumulative areas of signal void on axial images and the length of spinal canal obscuration on sagittal images. Three radiologists independently evaluated all images blindly. The inter-observer reliability was evaluated with inter-class coefficient. We defined patients with discomfortable symptoms caused by spinal instrumentation as spinal instrumentation adverse reaction.Visualizations of all periprosthetic anatomic structures were significantly better for SEMAC-VAT compared with standard imaging. For axial images, the area of signal void at the level of the instrumentation were statistically reduced with SEMAC-VAT TSE sequences than with standard TSE sequences for T2-weighted images (9.9 ± 2.6 cm vs 29.8 ± 14.7 cm, P < 0.001). For sagittal imaging, the length of spinal canal obscuration at the level of the instrumentation was reduced from 5.2 ± 2.0 cm to 1.2 ± 0.6 cm on T2-weighted images (P < 0.001), and from 4.8 ± 2.1 cm to 1.1 ± 0.5 cm on T1-weighted images with SEMAC-VAT sequences (P < 0.001). Interobserver agreement for visualization of anatomic structures and image quality was good for both SEMAC-VAT (k = 0.77 and 0.68, respectively) and standard (k = 0.74 and 0.80, respectively) imaging. The number of abnormal findings noted on SEMAC images (59 findings) was significantly higher than detected on standard images (40 findings). The incidence rate of spinal instrumentation adverse reaction was 38.81%.MR images with SEMAC-VAT can significantly reduce metal artifacts for spinal instrumentation and improve delineation of the instrumentation and periprosthetic region. Furthermore, SEMAC-VAT technique can improve diagnostic accuracy in patients with post-instrumentation spinal diseases.

Concepts: Series, Magnetic resonance imaging, Sequence, Anatomy, Human anatomy, UCI race classifications, Tour de Georgia, Limit of a sequence

10

Early marker-based metagenomic studies were performed without properly accounting for the effects of noise (sequencing errors, PCR single-base errors, and PCR chimeras). Denoising algorithms have been developed, but they were validated using data derived from mock communities, in which the true sequences were known. Since the algorithms were designed to be used in real community studies, it is important to evaluate the results in such cases. With this goal in mind, we processed a real 16S rRNA metagenomic dataset through five denoising pipelines. By reconstituting the sequence reads at each stage of the pipelines, we determined how the reads were being altered. In one denoising pipeline, AmpliconNoise, we found that the algorithm that was designed to remove pyrosequencing errors changed the reads in a manner inconsistent with the known spectrum of these errors, until one of the parameters was increased substantially from its default value. Additionally, because the longest read was picked as the representative for each cluster, sequences were added to the 3' ends of shorter reads that were often dissimilar from what had been removed by the truncations of the previous filtering step. In QIIME, the denoising algorithm caused a much larger number of changes to the reads unless the parameters were changed from their defaults. The denoising pipeline in mothur avoided some of these negative side-effects because of its strict default filtering criteria, but these criteria also greatly limited the sequence information produced at the end of the pipeline. We recommend that those using these denoising pipelines be cognizant of these issues and examine how their reads are being transformed by the denoising process as a component of their analysis.

Concepts: Ribosomal RNA, Data, 16S ribosomal RNA, 30S, Sequence, Real analysis, Fibonacci number, Limit of a sequence

8

The ability to accurately sequence long DNA molecules is important across biology, but existing sequencers are limited in read length and accuracy. Here, we demonstrate a method to leverage short-read sequencing to obtain long and accurate reads. Using droplet microfluidics, we isolate, amplify, fragment and barcode single DNA molecules in aqueous picolitre droplets, allowing the full-length molecules to be sequenced with multi-fold coverage using short-read sequencing. We show that this approach can provide accurate sequences of up to 10 kb, allowing us to identify rare mutations below the detection limit of conventional sequencing and directly link them into haplotypes. This barcoding methodology can be a powerful tool in sequencing heterogeneous populations such as viruses.

Concepts: DNA, Molecular biology, Biology, Series, Biotechnology, Sequence, Surface tension, Limit of a sequence