1,437 research outputs found

    Localization of Denaturation Bubbles in Random DNA Sequences

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    We study the thermodynamic and dynamic behaviors of twist-induced denaturation bubbles in a long, stretched random sequence of DNA. The small bubbles associated with weak twist are delocalized. Above a threshold torque, the bubbles of several tens of bases or larger become preferentially localized to \AT-rich segments. In the localized regime, the bubbles exhibit ``aging'' and move around sub-diffusively with continuously varying dynamic exponents. These properties are derived using results of large-deviation theory together with scaling arguments, and are verified by Monte-Carlo simulations.Comment: TeX file with postscript figure

    How to accelerate and increase user involvement in camping product development?

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    This study has been performed in the conception site of Decathlon Quechua Nature Hiking in France (Haute-Savoie, 74). It proposes the evaluation of two methods for accelerating and increasing user involvement in the product development process without reducing the quality. Co-creation, which consists in ideating products in collaboration with users, is performed in order to accelerate the ideation step. Fast prototyping experiments coupled with efficient feedback collection are proposed in order to make conception choices faster. These two methods are applied to the development of a product named inflatable shelves and evaluated in this context. A presentation of Decathlon traditional product development with timelines associated with each step is proposed in the beginning of this study. A comparison between the traditional approach and the development of the inflatable shelves gives an idea of the efficiency of the two methods used for accelerating the product development. Quality of the methods used is evaluated according to two definitions. Individual quality of each experiment is assessed by comparing the initial objectives and results obtained. Global quality of the product is determined by the user centeredness of ideation and conception choices. This study shows that co-creation and user involvement increase strongly the coherence of conception choices. User centeredness is at the heart of co-creation. Collaboration with users and potential customers is not the right solution for accelerating the ideation step but makes it more concrete. Fast prototyping experiments coupled with feedback collection from targeted populations have been performed. These experiments were based on continuous improvement of very rough prototypes, for function validations step by step. It reduced the conception time by half. Thanks to fast prototyping, conception step of inflatable shelves took four months instead of height for a traditional development. A new methodology for accelerating the product development process is proposed as a perspective of this study. It has been elaborated by redefining co-creation and fast prototyping real added values. Co-creation will be used for elaborating a coherent product brief and generate ideas for technical solutions. Fast prototyping experiments will be performed in order to collect feedback from experts and customers and increase the user centeredness of the product development

    Transition Metal Scaffolds as MRI Contrast Agents

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    Magnetic resonance imaging (MRI) is an important technique used throughout the medical field to gain improved clinical diagnostic ability. Often, different tissues can be weighted within the images if MRI contrast agents are used. Common clinical contrast agents use gadolinium to alter the T1 relaxation times of protons within surrounding tissues. Gadolinium(III), a lanthanide cation, has a grand seven unpaired electrons in its electronic configuration [Xe] 4f7. There are already a plethora of gadolinium chelate contrast agents available for medical use; however the sensitivity of these agents may be improved by increasing the rotational correlation time, tr. The goal of slower tumbling rates can be achieved by increasing their molecular weight. Thus, we propose attaching multiple gadolinium chelates to a central transition metal scaffold. The increase in molecular weight will alter the tr and improve the relaxation efficiency of the agent. These metal scaffolds will most likely include a Ru3O core

    The effects of mismatches on hybridization in DNA microarrays: determination of nearest neighbor parameters

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    Quantifying interactions in DNA microarrays is of central importance for a better understanding of their functioning. Hybridization thermodynamics for nucleic acid strands in aqueous solution can be described by the so-called nearest-neighbor model, which estimates the hybridization free energy of a given sequence as a sum of dinucleotide terms. Compared with its solution counterparts, hybridization in DNA microarrays may be hindered due to the presence of a solid surface and of a high density of DNA strands. We present here a study aimed at the determination of hybridization free energies in DNA microarrays. Experiments are performed on custom Agilent slides. The solution contains a single oligonucleotide. The microarray contains spots with a perfect matching complementary sequence and other spots with one or two mismatches: in total 1006 different probe spots, each replicated 15 times per microarray. The free energy parameters are directly fitted from microarray data. The experiments demonstrate a clear correlation between hybridization free energies in the microarray and in solution. The experiments are fully consistent with the Langmuir model at low intensities, but show a clear deviation at intermediate (non-saturating) intensities. These results provide new interesting insights for the quantification of molecular interactions in DNA microarrays.Comment: 31 pages, 5 figure

    Direct Observation of Node-to-Node Communication in Zeolitic Imidazolate Frameworks

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    Zeolitic imidazolate frameworks (ZIFs) with open-shell transition metal nodes represent a promising class of highly ordered light harvesting antennas for photoenergy applications. However, their charge transport properties within the framework, the key criterion to achieve efficient photoenergy conversion, are not yet explored. Herein, we report the first direct evidence of a charge transport pathway through node-to-node communication in both ground state and excited state ZIFs using the combination of paramagnetic susceptibility measurements and time-resolved optical and X-ray absorption spectroscopy. These findings provide unprecedented new insights into the photoactivity and charge transport nature of ZIF frameworks, paving the way for their novel application as light harvesting arrays in diverse photoenergy conversion devices

    depression and stroke risk

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    Evaluation of: Pan A, Okereke OI, Sun Q et al. Depression and incident stroke in women. Stroke 42(10), 2770ā€“2775 (2011). In the Nurses' Health Study, 80,574 women aged between 54 and 79 years, without a history of stroke, were followed-up from 2000 to 2006. In this cohort, depressive symptoms were assessed at multiple time points utilizing the Mental Health Index score (1992, 1996 and 2000), and clinically significant depressive symptoms were defined as a score ā‰¤52. A survey was carried out regarding antidepressant medication use biennially beginning in 1996, and physician-diagnosed depression was reported biennially from 2000. During this 6-year follow-up, 1033 incident strokes were documented. Having a history of depression was associated with an increased risk for total stroke, as well as the use of antidepressant medications with or without history of depression

    Thermodynamics of RNA/DNA hybridization in high density oligonucleotide microarrays

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    We analyze a series of publicly available controlled experiments (Latin square) on Affymetrix high density oligonucleotide microarrays using a simple physical model of the hybridization process. We plot for each gene the signal intensity versus the hybridization free energy of RNA/DNA duplexes in solution, for perfect matching and mismatching probes. Both values tend to align on a single master curve in good agreement with Langmuir adsorption theory, provided one takes into account the decrease of the effective target concentration due to target-target hybridization in solution. We give an example of a deviation from the expected thermodynamical behavior for the probe set 1091\_at due to annotation problems, i.e. the surface-bound probe is not the exact complement of the target RNA sequence, because of errors present in public databases at the time when the array was designed. We show that the parametrization of the experimental data with RNA/DNA free energy improves the quality of the fits and enhances the stability of the fitting parameters compared to previous studies.Comment: 11 pages, 16 figures - final version as publishe

    Hachimoji DNA and RNA: A genetic system with eight building blocks

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    Reported here are DNA and RNA-like systems built from eight (hachi-) nucleotide letters (-moji) that form four orthogonal pairs. This synthetic genetic biopolymer meets the structural requirements needed to support Darwinism, including a polyelectrolyte backbone, predictable thermodynamic stability, and stereoregular building blocks that fit a Schrƶdinger aperiodic crystal. Measured thermodynamic parameters predict the stability of hachimoji duplexes, allowing hachimoji DNA to double the information density of natural terran DNA. Three crystal structures show that the synthetic building blocks do not perturb the aperiodic crystal seen in the DNA double helix. Hachimoji DNA was then transcribed to give hachimoji RNA in the form of a functioning fluorescent hachimoji aptamer. These results expand the scope of molecular structures that might support life, including life throughout the cosmos

    Improved assay-dependent searching of nucleic acid sequence databases

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    Nucleic acid-based biochemical assays are crucial to modern biology. Key applications, such as detection of bacterial, viral and fungal pathogens, require detailed knowledge of assay sensitivity and specificity to obtain reliable results. Improved methods to predict assay performance are needed for exploiting the exponentially growing amount of DNA sequence data and for reducing the experimental effort required to develop robust detection assays. Toward this goal, we present an algorithm for the calculation of sequence similarity based on DNA thermodynamics. In our approach, search queries consist of one to three oligonucleotide sequences representing either a hybridization probe, a pair of Padlock probes or a pair of PCR primers with an optional TaqManā„¢ probe (i.e. in silico or ā€˜virtualā€™ PCR). Matches are reported if the query and target satisfy both the thermodynamics of the assay (binding at a specified hybridization temperature and/or change in free energy) and the relevant biological constraints (assay sequences binding to the correct target duplex strands in the required orientations). The sensitivity and specificity of our method is evaluated by comparing predicted to known sequence tagged sites in the human genome. Free energy is shown to be a more sensitive and specific match criterion than hybridization temperature
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