10,490 research outputs found

    Reply to Hagen & Sudarshan's Comment

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    We show that the argument in Phys Rev Lett 70 (1993) 1360 is correct and consistent, and that Hagen & Sudarshan's solution has inconsistency leading to non-vanishing commutators of [P1,P2][P^1, P^2] and [Pj,H][P^j, H] even in physical states. This proves that many of HS's statements in their Comment are based merely on incorrect guess, but not on careful algebra.Comment: one page, UMN-TH-1245/9

    Similarity solutions of Fokker-Planck equation with time-dependent coefficients

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    In this work, we consider the solvability of the Fokker-Planck equation with both time-dependent drift and diffusion coefficients by means of the similarity method. By the introduction of the similarity variable, the Fokker-Planck equation is reduced to an ordinary differential equation. Adopting the natural requirement that the probability current density vanishes at the boundary, the resulted ordinary differential equation turns out to be integrable, and the probability density function can be given in closed form. New examples of exactly solvable Fokker-Planck equations are presented, and their properties analyzed.Comment: 13 pages, 8 figures. Version to appear in Ann. Phys. Presentation improved. Discussions and figures of easy examples remove

    Computer simulations of block copolymer tethered nanoparticle self-assembly

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    We perform molecular simulations to study the self-assembly of block copolymer tethered cubic nanoparticles. Minimal models of the tethered nanoscale building blocks (NBBs) are utilized to explore the structures arising from self-assembly. We demonstrate that attaching a rigid nanocube to a diblock copolymer affects the typical equilibrium morphologies exhibited by the pure copolymer. Lamellar and cylindrical phases are observed in both systems but not at the corresponding relative copolymer tether block fractions. The effect of nanoparticle geometry on phase behavior is investigated by comparing the self-assembled structures formed by the tethered NBBs with those of their linear ABCABC triblock copolymer counterparts. The tethered nanocubes exhibit the conventional triblock copolymer lamellar and cylindrical phases when the repulsive interactions between different blocks are symmetric. The rigid and bulky nature of the cube induces interfacial curvature in the tethered NBB phases compared to their linear ABCABC triblock copolymer counterparts. We compare our results with those structures obtained from ABCABC diblock copolymer tethered nanospheres to further elucidate the role of cubic nanoparticle geometry on self-assembly.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87871/2/064905_1.pd

    Using workflow technology to manage flexible e-learning services

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    Workflow technology provides a suitable platform to define and manage the coordination of business process activities. We introduce a flexible e-learning environment – called Flex-eL – that has been built upon workflow technology. The workflow functionality of Flex-eL manages the coordination of learning and assessment activities of the course process between students and teaching staff. It provides a unique environment for teachers to design and develop process-centric courses and to monitor student progress. It allows students to learn at their own pace while observing the learning guidelines and checkpoints modeled into the course process by teaching staff. We also report on the successful deployment of the concept and system for university courses and our experiences from the implementation

    Microfluidic Preparation of Polymer-Nucleic Acid Nanocomplexes Improves Nonviral Gene Transfer

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    As the designs of polymer systems used to deliver nucleic acids continue to evolve, it is becoming increasingly apparent that the basic bulk manufacturing techniques of the past will be insufficient to produce polymer-nucleic acid nanocomplexes that possess the uniformity, stability, and potency required for their successful clinical translation and widespread commercialization. Traditional bulk-prepared products are often physicochemically heterogeneous and may vary significantly from one batch to the next. Here we show that preparation of bioreducible nanocomplexes with an emulsion-based droplet microfluidic system produces significantly improved nanoparticles that are up to fifty percent smaller, more uniform, and are less prone to aggregation. The intracellular integrity of nanocomplexes prepared with this microfluidic method is significantly prolonged, as detected using a high-throughput flow cytometric quantum dot Förster resonance energy transfer nanosensor system. These physical attributes conspire to consistently enhance the delivery of both plasmid DNA and messenger RNA payloads in stem cells, primary cells, and human cell lines. Innovation in processing is necessary to move the field toward the broader clinical implementation of safe and effective nonviral nucleic acid therapeutics, and preparation with droplet microfluidics represents a step forward in addressing the critical barrier of robust and reproducible nanocomplex productio

    Structure-based Discovery of Novel Small Molecule Wnt Signaling Inhibitors by Targeting the Cysteine-rich Domain of Frizzled.

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    Frizzled is the earliest discovered glycosylated Wnt protein receptor and is critical for the initiation of Wnt signaling. Antagonizing Frizzled is effective in inhibiting the growth of multiple tumor types. The extracellular N terminus of Frizzled contains a conserved cysteine-rich domain that directly interacts with Wnt ligands. Structure-based virtual screening and cell-based assays were used to identify five small molecules that can inhibit canonical Wnt signaling and have low IC50 values in the micromolar range. NMR experiments confirmed that these compounds specifically bind to the Wnt binding site on the Frizzled8 cysteine-rich domain with submicromolar dissociation constants. Our study confirms the feasibility of targeting the Frizzled cysteine-rich domain as an effective way of regulating canonical Wnt signaling. These small molecules can be further optimized into more potent therapeutic agents for regulating abnormal Wnt signaling by targeting Frizzled
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